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Item 1A. Risk Factors

2025-03-20 compared with 2024-03-21 · 531 added, 487 removed, 1138 unchanged (47% of the section changed)

An investment in our ADSs involves a high degree of risk.

You should carefully consider the risks and uncertainties described below, and all other information appearing elsewhere in this Annual Report, including our consolidated financial statements and the related notes hereto, before making an investment decision regarding our securities.

The occurrence of any of the events or developments described below could harm our business, financial condition, results of operations and growth prospects.

Our business is subject to numerous risks.

You should carefully consider and evaluate each of the following factors as well as the other information in this Annual Report on Form 10-K, including our financial statements and related notes, in evaluating our business and prospects.

The risks and uncertainties described below are not the only ones we face.

Additional risks and uncertainties not presently known to us or that we currently consider immaterial may also impair our business operations.

If any of the following risks actually occur, our business and financial results could be harmed.

In that case, the trading price our ADSs could decline.

Risks Related to Our Financial Position and Need For Capital

We have incurred significant losses in every year since our inception.

We expect to continue to incur losses over the next several years and may never achieve or maintain profitability.

We are a clinical-stage biopharmaceutical company with a limited operating history, and we have incurred significant net losses since our inception in 2014.

We have incurred losses o f $208.4 million, $148.8 million and $142.1 million for the years ended December 31, 2023, 2022 and 2021, respectively.

We are an early commercial-stage biopharmaceutical company and have incurred significant losses since our inception.

We expect to continue to incur losses for the foreseeable future.

We are an early commercial-stage biopharmaceutical company with a limited operating history, and we have incurred significant net losses since our inception in 2014.

We have incurred losses o f $220.7 million and $208.4 million for the years ended December 31, 2024 and 2023, respectively.

As of December 31, 2024, we had an accumulated deficit of $1,099.2 million.

We have funded our operations to date primarily with proceeds from the sale of our equity securities, including ADSs, licensing and collaboration arrangements and strategic financing.

We currently have no products approved for commercial sale, and while we have generated revenue from licensing, we are devoting substantially all of our financial resources and efforts to research and development of our programmed T cell product candidates and T cell programming technologies, as well as to building out our commercial and manufacturing infrastructure.

We currently have one product, AUCATZYL (obe-cel ) , approved for commercial sale, and while we have generated revenue from licensing, we are devoting substantially all of our financial resources and efforts to manufacturing and commercializing AUCATZYL and for the research and development of our other programmed T cell product candidates and T cell programming technologies.

Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront operating and capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effect or an acceptable safety profile, gain regulatory approval and become commercially viable.

The FDA has accepted our BLA for obe-cel for patients with relapsed/refractory (r/r) Adult B-Cell ALL, and has set a target PDUFA action date of November 16, 2024.

Should the FDA not grant us marketing approval, we are unsuccessful in our commercialization efforts or the market does not accept our product, we may not generate revenue.

We expect that it could take several years until any of our other product candidates receive marketing approval and are commercialized, and we may never be successful in obtaining marketing approval and commercializing any of our product candidates, including obe-cel.

Should we be unsuccessful in our commercialization efforts for AUCATZYL or if the rates of market acceptance do not meet our expectations, we may not generate sufficient revenue.

We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future.

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We anticipate that our expenses will increase substantially as we:

• expand our sales, marketing and distribution infrastructure to commercialize AUCATZYL/obe-cel and any other product candidate for which we may obtain regulatory approval;

• make required milestone, royalty and revenue sharing payments to third parties under license and collaboration agreements;

• continue to scale up internal and external manufacturing capacity with the aim of securing sufficient quantities to meet our capacity requirements for commercialization of AUCATZYL and clinical trials of our other product candidates;

• continue our ongoing and planned research and development of our current programmed T cell product candidates for the treatment of hematological cancers, solid tumors and autoimmune diseases;

• initiate preclinical studies and clinical trials for any additional product candidates that we may pursue in the future, including our planned development of additional T cell therapies for the treatment of hematological cancers, solid tumors and autoimmune diseases;

• seek to discover and develop additional product candidates and further expand our clinical product pipeline;

• seek regulatory approvals for any product candidates that successfully complete clinical trials;

• continue to scale up internal and external manufacturing capacity with the aim of securing sufficient quantities to meet our capacity requirements for clinical trials and potential commercialization;

• establish sales, marketing and distribution infrastructure to commercialize any product candidate for which we may obtain regulatory approval;

• make required milestone and royalty payments to UCLB or other third parties, under license agreements pursuant to which we were granted some of our intellectual property rights;

• make required sales milestone and royalty payments to BXLS V Autobahn LP (“Blackstone”) under our collaboration and financing agreement relating to obe-cel, our lead product, and other collaboration products for B cell malignancies;

• make required milestone payments to Miltenyi under our sublicense agreement relating to certain proprietary technologies incorporated in certain of our manufacturing processes;

• make required revenue share interest payments to BioNTech relating to obe-cel under our license and option agreement;

• develop, maintain, expand and protect our intellectual property portfolio;

• acquire or in-license other product candidates and technologies;

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• hire additional clinical, quality control and manufacturing personnel;

• add clinical, operational, financial and management information systems and personnel, including personnel to support our product development and planned future commercialization efforts;

• add clinical, operational, financial and management information systems and personnel, including personnel to support the commercial development of AUCATZYL, as well as our other product development and future commercialization efforts;

• expand our operations in the United States, Europe and other geographies;

• incur additional legal, accounting and other expenses associated with operating as a public company.

To become and remain profitable, we must succeed in developing and eventually commercializing products that generate significant revenue.

This will require us to be successful in a range of challenging activities, including completing preclinical studies and clinical trials of our product candidates, preparing a satisfactory filing package for regulatory authorities, obtaining regulatory approval, manufacturing, marketing and selling any products for which we may obtain regulatory approval, as well as discovering and developing additional product candidates.

To become and remain profitable, we must succeed in commercializing AUCATZYL and developing and eventually commercializing other products that generate significant revenue.

This will require us to be successful in a range of challenging activities, including marketing and selling AUCATZYL and any future products for which we may obtain regulatory approval, completing preclinical studies and clinical trials of our product candidates, preparing a satisfactory filing package for regulatory authorities, obtaining regulatory approval, manufacturing, marketing and selling any products for which we may obtain regulatory approval, as well as discovering and developing additional product candidates.

We may never succeed in these activities and, even if we do, may never generate revenues that are significant enough to achieve profitability.

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A decline in the value of our ADSs could also cause you to lose all or part of your investment.

Our limited operating history may make it difficult for you to evaluate the success of our business to date and to assess our future viability.

We are a clinical-stage biopharmaceutical company with a limited operating history.

As an organization, we have not demonstrated an ability to successfully obtain regulatory approvals, manufacture our product candidates at commercial scale or arrange for a third party to do so on our behalf, conduct sales and marketing activities necessary for successful commercialization, or obtain reimbursement in the countries of sale.

We may encounter unforeseen expenses, difficulties, complications, and delays in achieving our business objectives.

Our limited history as an operating company makes any assessment of our future success or viability subject to significant uncertainty.

If we do not address these risks successfully or are unable to transition at some point from a company with a research and development focus to a company capable of supporting commercial activities, then our business will suffer.

We will need additional funding to complete the development of our product candidates, which may not be available on acceptable terms, if at all.

We will require substantial additional funding to meet our financial needs and to pursue our business objectives.

We will need additional funding to successfully commercialize AUCATZYL and to complete the development of and commercialize our other product candidates, which may not be available on acceptable terms, if at all.

Unless and until we are able to successfully commercialize AUCATZYL and achieve significant revenue from sales, we will require substantial additional funding to meet our financial needs and to pursue our business objectives.

If we are unable to raise capital when needed, we could be forced to delay, reduce or altogether cease our product development programs or commercialization efforts.

Since our inception, we have devoted substantially all of our resources to fund the operating expenses and capital expenditure requirements associated with the research and development of our product candidates.

These programs are described in greater detail in the “Business” section of this Annual Report.

Our current funding may only be sufficient to fund obe-cel through initial commercial launch, assuming certain timelines on successful regulatory approval, and we will need to raise additional capital to reach profitability as well as to complete the development and commercialization of our other programmed T cell product candidates, and in connection with our continuing operations, strategy and other planned activities.

Even once we begin to generate revenue from sales of AUCATZYL, we will need to raise additional capital to reach profitability as well as to complete the development and commercialization of our other programmed T cell product candidates, and in connection with our continuing operations, strategy and other planned activities.

Our future capital requirements will depend on many factors, including:

• our ability to execute our commercialization strategies for and generate revenue from sales of AUCATZYL and, if approved, our other product candidates;

• the progress, results and costs of laboratory testing, manufacturing, and preclinical and clinical development of our current and future product candidates;

• the timing and amounts of any milestone or royalty payments we may be required to make under current or future license or collaboration agreements;

• the timing and amounts of any milestone, royalty payments or revenue sharing payments we may be required to make under current or future license or collaboration agreements;

• the costs of leasing, building out, equipping, and operating the facilities necessary to research, develop, manufacture and commercialize our product candidates, as well as to support our continuing operations;

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• the costs, timing and outcome of regulatory review of our product candidates;

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• the costs and timing of future commercialization activities, including product manufacturing, marketing, sales and distribution, for any of our product candidates for which we receive marketing approval;

• the revenue, if any, received from commercial sales of our product candidates for which we receive marketing approval;

• the costs and timing of commercialization activities, including product manufacturing, marketing, sales and distribution, for any future product candidates for which we receive marketing approval;

• the costs and timing of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending any intellectual property-related claims;

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Identifying potential product candidates and conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, and we may never generate the necessary data or results required to obtain regulatory approval and achieve product sales.

In addition, our product candidates, if approved, may not achieve commercial success.

Our product revenues, if any, will be derived from sales of product candidates that we do not expect to be commercially available until late 2024 at the earliest, in the case of our existing lead program and, with respect to other pipeline programs, for up to several years, if at all.

In addition, AUCATZYL, or our other product candidates, if approved, may not achieve commercial success.

Our product revenues in the near term will be derived primarily from sales of AUCATZYL in the US, as we that we do not expect to generate material revenues from obe-cel in other jurisdictions or from other pipeline programs, for up to several years, if at all.

Accordingly, we will need to continue to rely on additional financing to achieve our business objectives.

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We have incurred substantial obligations under license and collaboration agreements, which could impair our flexibility and access to other capital and adversely affect our financial position, and our business would be adversely affected if we were unable to meet our obligations under these and similar future agreements.

In November 2021, we entered into a collaboration agreement with Blackstone (the “Blackstone Collaboration Agreement”) pursuant to which Blackstone has agreed to pay us up to $150 million to support the continued development and, following approval, commercialization of obe-cel and next-generation product candidates (obe-cel and such next-generation products, collectively, the “Collaboration Products”) in exchange for our agreement to make substantial payments to Blackstone following approval of such products.

In November 2021, we entered into a collaboration agreement with Blackstone (the “Blackstone Collaboration Agreement”) pursuant to which Blackstone agreed to pay us up to $150 million to support the continued development and commercialization of AUCATZYL/obe-cel and next-generation product candidates (collectively, the “Collaboration Products”) in exchange for our agreement to make substantial payments to Blackstone following approval of such Collaboration Products.

These payments include a single-digit percentage payment on worldwide net sales of (i) the Collaboration Products in any indication and (ii) AUTO3 for the treatment of B-cell leukemias and lymphomas, by us and any of our licensees, as well as sales milestone payments relating to such net sales.

Such payments to Blackstone could increase our cash requirements and could impair our liquidity.

As of December 31, 2023, Blackstone has paid $120 million to us under the terms of the Blackstone Collaboration Agreement.

Under the BioNTech License Agreement with BioNTech entered into in February 2024, we have agreed to pay BioNTech a low single-digit percentage of annual net revenue of obe-cel which may be increased up to a mid-single digit percentage in exchange for milestone payments of up to $100 million in the aggregate on achievement of certain regulatory events for specific new indications upon BioNTech's election.

Such payments to BioNTech could increase our cash requirements and could impair our liquidity.

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In connection with the Collaboration Agreement, Blackstone was granted a security interest in substantially all of our assets.

The Collaboration Agreement also contains negative covenants that restrict us from (a) granting liens on certain of our assets, including liens on the intellectual property relating to the Collaboration Products, except for certain permitted liens, (b) making distributions or dividends, except for certain permitted distributions, (c) entering into development or commercialization license transactions with respect to the Collaboration Products, except that we are permitted to enter into any such development or commercialization license transactions with certain pharmaceutical companies, including those companies that have annual sales in excess of an agreed threshold, (d) consummating certain change in control transactions, (e) selling royalties or entering into similar financials transactions involving the sale of revenues or royalties, or (f) acquiring subsidiaries without joining such subsidiary as a party to the Blackstone Collaboration Agreement.

These restrictions could inhibit our ability to pursue our business strategies and may limit our ability to, among other things, incur secured indebtedness, encumber assets, pay dividends or make other distributions to holders of our capital stock, license-out the Collaboration Products, complete mergers or acquisitions, or sell royalties.

As of December 31, 2024, Blackstone has paid us the full $150 million under the terms of the Blackstone Collaboration Agreement, including the final payment of $30 million in the fourth quarter of 2024 following regulatory approval of AUCATZYL.

If we default under our obligations under the Blackstone Collaboration Agreement, we will be obligated to pay Blackstone liquidated damage payments in excess of the development payment paid by Blackstone.

If we fail to make such payments, Blackstone could elect to exercise its remedies in respect of the security interest, which would seriously harm our business and ability to continue as a going concern.

Under the BioNTech License Agreement with BioNTech entered into in February 2024, we also agreed to pay BioNTech a low single-digit percentage of annual net revenue of AUCATZYL/obe-cel, which may be increased up to a mid-single digit percentage, in exchange for milestone payments of up to $100 million in the aggregate on achievement of certain regulatory events for specific new indications upon BioNTech's election.

Such payments to BioNTech could increase our cash requirements and could impair our liquidity.

Risks Related to the Commercialization of AUCATZYL and Our Other Product Candidates

AUCATZYL and any other product candidates, if approved, may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success, thereby limiting our potential to generate revenue.

AUCATZYL and any other product candidates, if approved, may not achieve market acceptance among physicians, patients, hospitals, including pharmacy directors, and third-party payors and, ultimately, may not be commercially successful.

If these products do not achieve an adequate level of acceptance, we may not generate significant product revenue and may not become profitable.

FDA’s investigation into secondary malignancies associated with CAR T cell therapies and other similar actions could result in increased government regulation, unfavorable public perception and publicity, stricter labeling requirements for AUCATZYL and those product candidates that are approved, and a decrease in demand for AUCATZYL or any such product candidates.

The degree of market acceptance of AUCATZYL, and any other product candidates, if approved for commercial sale, will depend on a number of factors, including:

• the timing of market introduction of those products compared to competitive products;

• the continued safety and efficacy of those products;

• the clinical indications for which our product candidates are approved;

• physicians, hospitals, cancer treatment centers, and patients considering our product and product candidates as a safe and effective treatment;

• hospitals and cancer treatment centers establishing the infrastructure required for the administration of redirected T cell therapies;

• the potential and perceived advantages of our product and product candidates over alternative treatments;

• the prevalence and severity of any side effects;

• product labeling or product insert requirements of the FDA, the European Commission or other regulatory authorities;

• limitations or warnings contained in the labeling approved by the FDA or the European Commission;

• the cost of treatment in relation to alternative treatments;

• the amount of upfront costs or training required for physicians to administer our product and product candidates;

• the availability of coverage, adequate reimbursement, and pricing by third-party payors and government authorities;

• the willingness and ability of patients to pay out-of-pocket in the absence of comprehensive coverage and adequate reimbursement by third-party payors and government authorities;

• relative convenience and ease of scheduling and administration, including as compared to alternative treatments and competitive therapies;

• the effectiveness of our sales and marketing efforts and distribution support.

Our efforts to educate physicians, patients, third-party payors and others in the medical community on the benefits of AUCATZYL and our other product candidates, if approved, may require significant resources and may never be successful.

Such efforts may require more resources than are typically required due to the complexity and uniqueness of our product candidates.

Because we expect sales of AUCATZYL and any future products, if approved, to generate substantially all of our product revenue for the foreseeable future, the failure of those products to find market acceptance would harm our business and could require us to seek additional financing.

In addition, although we are not utilizing embryonic stem cells or replication competent vectors, adverse publicity due to the ethical and social controversies surrounding the therapeutic use of such technologies, and reported side effects from any clinical trials using these technologies or the failure of such trials to demonstrate that these therapies are safe and effective, may limit market acceptance our product candidates.

Even if our products achieve market acceptance, we may not be able to maintain that market acceptance over time if new products or technologies are introduced that are more favorably received than our products, are more cost effective or render our products obsolete.

If we are unable to fully develop our sales, marketing and distribution capability on our own , or enter into sales, marketing and distribution agreements with third parties, we may not be successful in commercializing AUCATZYL, or our other product candidates, if and when approved.

We have spent significant resources to build our global commercialization capabilities in anticipation of the commercial launch of AUCATZYL.

To achieve commercial success for AUCATZYL or any other product candidate for which we may obtain marketing approval, we will need to maintain a sales and marketing organization and establish logistics and distribution processes to commercialize and deliver our product candidates to patients and healthcare providers.

The development of sales, marketing and distribution capabilities has required and will continue to require substantial resources, will be time-consuming and could delay any product launch.

We currently have limited resources compared to some of our competitors, and the continued development of our own commercial organization to market our medicines and any additional medicines we may acquire will be expensive and time-consuming.

In addition, not all members of our sales force have promoted medicines for treatment of adult r/r B-ALL prior to the launch of AUCATZYL.

We have spent and will continue to expend significant time and resources to train our sales force to be able to educate physicians on the benefits of prescribing and pharmacists dispensing AUCATZYL.

Furthermore, we must train our sales force to ensure that a consistent and appropriate message about AUCATZYL is being delivered to our potential customers.

We may experience turnover of the sales representatives that we hired or will hire, requiring us to train new sales representatives.

If we are unable to effectively train our sales force and equip them with effective materials, including medical and sales literature to help them inform and educate physicians about the benefits of AUCATZYL and its proper administration and label indication, as well as our patient assistance programs, our efforts to successfully commercialize AUCATZYL could jeopardize, which could have a material adverse effect on our financial condition, share price and operations.

If we are unable or decide not to establish internal sales, marketing and distribution capabilities, in any territory, we would have to pursue collaborative arrangements regarding the sales and marketing of our products.

However, we may not be successful in entering into arrangements with third parties to sell, market and distribute AUCATZYL/obe-cel or our other product candidates or may be unable to do so on terms that are favorable to us, or if we are able to do so, that they would be effective and successful in commercializing our products.

Our product revenues and our profitability, if any, would likely be lower than if we were to sell, market and distribute AUCATZYL/obe-cel and any other product candidates that we develop ourselves.

In addition, we would have limited control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market AUCATZYL/obe-cel and any of our other product candidates effectively.

The incidence and prevalence for target patient populations for AUCATZYL and our other product candidates have not been established with precision.

If the market opportunities for AUCATZYL and our other product candidates are smaller than we estimate, our revenue and ability to achieve profitability will be adversely affected, possibly materially.

The total addressable market opportunity for AUCATZYL and our other product candidates will ultimately depend upon, among other things, acceptance by the medical community and patient access, product pricing and reimbursement as well as expansion into additional markets.

The number of patients who may benefit from AUCATZYL or our other future products may turn out to be lower than expected, patients may not be otherwise amenable to treatment with our products, or new patients may become increasingly difficult to identify or gain access to, all of which would adversely affect our results of operations and our business.

We may not be successful in our efforts to identify additional product candidates.

Due to our limited resources and access to capital, we must prioritize development of certain product candidates, which may prove to be the wrong choice and may adversely affect our business.

We operate in a rapidly changing industry and face significant competition, which may result in others discovering, developing or commercializing products before or more successfully than we do.

The development and commercialization of new biopharmaceutical products is highly competitive and subject to rapid and significant technological advancements.

We face competition from major multi-national pharmaceutical companies, biotechnology companies and specialty pharmaceutical companies with respect to our current and future product candidates that we may develop and commercialize in the future.

There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of product candidates for the treatment of cancer.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies.

Potential competitors also include academic institutions, government agencies and other public and private research organizations.

Due to their promising clinical therapeutic effect in clinical exploratory trials, engineered T cell therapies, redirected T cell therapies in general and antibody-drug conjugates are being pursued by multiple biotechnology and pharmaceutical companies, including Novartis AG (“Novartis”), Gilead Sciences, Inc.

(“Gilead”), Bristol-Myers Squibb (“BMS”), and Janssen Biotech Inc.

Our competitors may succeed in developing, acquiring or licensing technologies and products that are more effective, more effectively marketed and sold or less costly than any product candidates that we may develop, which could render our product candidates non-competitive and obsolete.

We have received marketing approval from the FDA for AUCATZYL for the treatment of adult r/r B-ALL.

Novartis, Gilead and BMS have also received marketing approval for anti-CD19 CAR T cell therapies.

Gilead's therapy was approved for the treatment of adult ALL in October 2021.

AUCATZYL is expected to compete directly with these companies and therapies.

In addition, some companies, such as Cellectis, Inc., Les Laboratoires Servier SAS, Allogene Therapeutics Inc., Lyell Immunopharma, Cargo Therapeutics and Crispr Therapeutics AG are pursuing allogenic T cell products that could compete with our programmed T cell product candidates.

Novartis, Gilead and BMS may be successful in establishing a strong market position for their CD19-targeted CAR T cell products, and we may not be able to compete effectively against these therapies once they have been established.

Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive or better reimbursed than any products that we may commercialize.

Our competitors also may obtain FDA, European Commission or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position for either the product or a specific indication before we are able to enter the market.

Many of our competitors, either alone or with their strategic collaborators, have substantially greater financial, technical and human resources than we do.

Accordingly, our competitors may be more successful than we are in obtaining approval for treatments and achieving widespread market acceptance, which may render our treatments obsolete or non-competitive.

Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated among a smaller number of our competitors.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical studies, as well as in acquiring technologies complementary to, or necessary for, our programs.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

Coverage and adequate reimbursement may not be available for AUCATZYL or our current or any future product candidates, which could make it difficult for us to sell profitably, if approved.

Market acceptance and sales of our product and any product candidates that we commercialize, if approved, will depend in part on the extent to which reimbursement for these products and related treatments will be available from third-party payors, including government health administration authorities, managed care organizations and private health insurers.

Third-party payors decide which therapies they will pay for and establish reimbursement levels.

Third-party payors in the United States often rely upon Medicare coverage policy and payment limitations in setting their own coverage and reimbursement policies.

However, decisions regarding the extent of coverage and amount of reimbursement to be provided for our product or any product candidates that we develop, once approved, will be made on a payor-by-payor basis.

One payor’s determination to provide coverage for a drug does not assure that other payors will also provide coverage for the drug.

Additionally, a third-party payor’s decision to provide coverage for a therapy does not imply that an adequate reimbursement rate will be approved.

Third-party payors are increasingly challenging the price, examining the medical necessity and reviewing the cost-effectiveness of medical products, therapies and services, in addition to questioning their safety and efficacy.

We may incur significant costs to conduct expensive pharmaco-economic studies in order to demonstrate the medical necessity and cost-effectiveness of our product, and product candidates, once approved, in addition to the costs required to obtain FDA approvals.

Our product and product candidates, once approved, may not be considered medically necessary or cost-effective by third-party payors.

Each payor determines whether or not it will provide coverage for a therapy, what amount it will pay the manufacturer for the therapy, and on what tier of its list of covered drugs, or formulary, it will be placed.

The position on a payor’s formulary, generally determines the co-payment that a patient will need to make to obtain the therapy and can strongly influence the adoption of such therapy by patients and physicians.

Patients who are prescribed treatments for their conditions and providers prescribing such services generally rely on third-party payors to reimburse all or part of the associated healthcare costs.

Patients are unlikely to use our products, and providers are unlikely to prescribe our products, unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of our products and their administration.

Therefore, coverage and adequate reimbursement is critical to new medical product acceptance.

A primary trend in the U.S.

healthcare industry and elsewhere is cost containment.

Third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications.

We cannot be sure that coverage and reimbursement will be available for our product or any product candidates and, if reimbursement is available, what the level of reimbursement will be.

Even if favorable coverage and reimbursement status is attained for our product or any product candidates for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Inadequate coverage and reimbursement may impact the demand for, or the price of, any drug for which we obtain marketing approval.

If coverage and adequate reimbursement are not available, or are available only to limited levels, we may not be able to successfully commercialize our current and any future product candidates that we develop.

Additionally, we are developing a proprietary diagnostic test for use with our product and certain of our product candidates.

We will be required to obtain coverage and reimbursement for this test separate and apart from the coverage and reimbursement we seek for our products and product candidates, if approved.

There is significant uncertainty regarding our ability to obtain coverage and adequate reimbursement for this proprietary diagnostic test for reasons similar to those applicable to our product and product candidates, if approved.

Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of AUCATZYL or any other products that we may develop.

We face an inherent risk of product liability exposure related to the testing of our product and product candidates in human clinical trials and will face an even greater risk if we commercially sell any products that we may develop.

If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we will incur substantial liabilities.

Regardless of merit or eventual outcome, liability claims may result in:

• reduced resources of our management to pursue our business strategy;

• decreased demand for any product candidates or products that we may develop;

• injury to our reputation and significant negative media attention;

• withdrawal of clinical trial participants;

• initiation of investigations by regulators;

• product recalls, withdrawals or labeling, marketing or promotional restrictions;

• significant costs to defend the resulting litigation;

• substantial monetary awards paid to clinical trial participants or patients;

• loss of revenue;

• the inability to commercialize any products that we may develop.

We currently hold £10 million in product liability insurance coverage in the aggregate, with a per incident limit of £10 million, w hich may not be adequate to cover all liabilities that we may incur.

We may need to increase our insurance coverage as we expand our clinical trials or if we commence commercialization of our product candidates.

Insurance coverage is increasingly expensive.

We may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.

Risks Related to the Development of Our Product Candidates

All of our product candidates are in clinical development or in preclinical development.

Our product candidates are in clinical development or in preclinical development.

If we are unable to advance our product candidates through clinical development, obtain regulatory approval and ultimately commercialize our product candidates, or experience significant delays in doing so, our business will be materially harmed.

We have established clinical proof-of-concept for only one of our product candidates.

There is no assurance that our current or any other future clinical trials of our product candidates will be successful or will generate positive clinical data, and we may not receive marketing approval from the FDA, or other regulatory agencies, including the European Commission, for any of our product candidates.

Other than AUCATZYL, the rest of our product pipeline is in clinical or preclinical development.

We have established clinical proof-of-concept for only one of our products, AUCATZYL, which recently received FDA approval in r/r B-ALL.

There is no assurance that our current or any other future clinical trials of our product candidates will be successful or will generate positive clinical data.

Although we received marketing approval from the FDA for AUCATZYL in the US, and have submitted MAAs to the MHRA and EMA, we may not be successful in receiving marketing approval from these regulatory agencies, including the European Commission, for obe-cel or for any of our other product candidates.

In order to commence a clinical trial in the United States, we must submit an IND to the FDA and have the IND application go into effect.

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An investigator may not administer a drug candidate to human subjects until the IND goes into effect.

Similar requirements apply to our conduct of trials in the UK and EU.

We are sponsoring active, recruiting clinical trials for two of our product candidates, obe-cel (AUTO1), and AUTO4.

We are also collaborating with our academic partner UCL to support clinical trials sponsored by them of our product candidates (obe-cel, AUTO1/22, AUTO6NG and AUTO8).

Similar requirements apply to our conduct of trials in the U.K.

We are sponsoring active, recruiting clinical trials for obe-cel in additional indications and AUTO4.

We are also collaborating with our academic partner UCL to support clinical trials sponsored by them of obe-cel in additional indications, AUTO1/22, AUTO6NG and AUTO8.

In addition, patients who have received an investigational product developed by us will be evaluated for long-term safety and disease response in a long-term follow-up protocol.

There can be no assurance that the FDA, the competent authorities of EU Member States or other regulatory agencies will permit any future clinical trial application to go into effect in a timely manner or at all.

and EU regulations require parties seeking regulatory approval for product candidates in adult indications to define a development plan for such candidate in pediatric indications, commonly referred to as a PSP in the United States.

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• manufacturing our product candidates at an acceptable cost;

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• maintaining and growing an organization of scientists, medical professionals and business people who can develop and commercialize our products and technology.

Many of these factors are beyond our control, including the time needed to adequately complete clinical testing and the regulatory submission process.

It is possible that none of our product candidates will ever obtain regulatory approval, even if we expend substantial time and resources seeking such approval.

It is possible that none of our other product candidates will ever obtain regulatory approval, even if we expend substantial time and resources seeking such approval.

If we do not achieve one or more of these factors in a timely manner or at all, or any other factors impacting the successful development of biopharmaceutical products, we could experience significant delays or an inability to successfully develop our product candidates, which would materially harm our business.

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We have concentrated our research and development efforts on our T cell technology platform using our expertise in disease biology and cell programming, and our future success is highly dependent on the successful development and manufacture of our programmed T cell product candidates.

We do not currently have any approved or commercialized products.

Some of our product candidates employ a dual-targeting mechanism.

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Additionally, because our technology involves the genetic modification of patient cells ex vivo , we are subject to additional regulatory challenges and risks, including regulatory requirements governing genetically modified organisms that have changed frequently and will likely continue to change in the future, and that may limit or delay our ability to import our product candidates into certain countries for use in clinical trials or for commercial sale even if we receive applicable marketing approvals.

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Moreover, public perception and awareness of T cell therapy safety issues may adversely influence the willingness of subjects to participate in clinical trials of our product candidates, or if approved, of physicians to prescribe our products.

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Based on these and other factors, hospitals and payors may decide that the benefits of this new therapy do not or will not outweigh its costs.

Our future success is highly dependent on the regulatory approval of our current clinical-stage programmed T cell product candidates and our preclinical programs.

All of our product candidates will require significant clinical or preclinical testing before we can seek regulatory approval for and launch a product commercially.

We do not have any products that have gained regulatory approval.

Our business is substantially dependent on our ability to obtain regulatory approval for, and, if approved, to successfully commercialize our programmed T cell product candidates.

Our future success is highly dependent on the regulatory approval of our other clinical-stage programmed T cell product candidates and our preclinical programs.

Our product candidates will require significant clinical or preclinical testing before we can seek regulatory approval for and launch a product commercially.

Although we have received FDA approval for AUCATZYL in r/r B-ALL, our business remains substantially dependent on our ability to successfully obtain regulatory approval for, and, if approved, to successfully commercialize our other programmed T cell product candidates.

We cannot commercialize product candidates in the United States without first obtaining regulatory approval for the product from the FDA;

similarly, we cannot commercialize product candidates in countries outside of the United States without obtaining regulatory approval from comparable regulatory authorities in relevant jurisdictions, such as the European Commission in the EU (granted on the basis of a positive opinion from the CHMP of the EMA).

Additionally, to file for licensure in any jurisdiction outside of the UK we must first receive GMP certification from the MHRA.

Additionally, to file for licensure in any jurisdiction outside of the U.K.

we must first receive GMP certification from the MHRA.

Before obtaining regulatory approvals for the commercial sale of any product candidate for a particular indication, if approved, we must demonstrate with substantial evidence gathered in preclinical and clinical studies, that the product candidate is safe and effective for that indication and that the manufacturing facilities, processes and controls are adequate with respect to such product candidate.

The obe-cel Regenerative Medicine Advanced Therapy (“RMAT”) designation was submitted to FDA in February 2022 and was granted in April 2022.

Similarly, in the UK, Autolus utilized the MHRA Innovative Licensing and Access Pathway (“ILAP”) and applied for ‘Innovative Passport’ designation (“Innovation Passport”) which aims to accelerate the timeline to regulatory approval.

The UK ILAP designation in r/r adult B-ALL was granted in June 2021.

Additionally, EMA PRIME designation in r/r B-ALL was obtained in March 2021.

Similarly, in the U.K., Autolus utilized the MHRA Innovative Licensing and Access Pathway (“ILAP”) and applied for ‘Innovative Passport’ designation (“Innovation Passport”) which aims to accelerate the timeline to regulatory approval.

ILAP designation in r/r B-ALL was granted in June 2021 and we submitted an MAA to the MHRA at the end of July 2024.

Additionally, EMA PRIME designation in r/r B-ALL was obtained in March 2021 and we submitted an MAA to the EMA, which was accepted in April 2024.

Moreover, Orphan Designation in B-ALL was granted by the FDA in November 2019 and by the European Commission in March 2022.

To date, we have had only limited interaction with the FDA, MHRA, the EMA and the European Commission, regarding our product candidates.

Prior to seeking approval for any of our product candidates, we will need to confer with the FDA, MHRA, the EMA and other regulatory authorities regarding the design of our clinical trials and the type and amount of clinical data necessary to seek and gain approval for our product candidates.

Prior to seeking approval for any of our other product candidates, we will need to confer with the FDA, MHRA, the EMA and other regulatory authorities regarding the design of our clinical trials and the type and amount of clinical data necessary to seek and gain approval for our product candidates.

The time required to obtain approval by the FDA, MHRA, the European Commission and other regulatory authorities is unpredictable but typically takes many years following the commencement of preclinical studies and clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities.

In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions.

It is possible that none of our existing product candidates or any future product candidates will ever obtain regulatory approval.

It is possible that none of our other existing product candidates or any future product candidates will ever obtain regulatory approval.

Our product candidates could fail to receive regulatory approval from the FDA, MHRA, the European Commission or other regulatory authorities and, consequently, fail to achieve suitable commercial success for many reasons, including:

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• augmentation of the requirements to satisfy facility qualification or licensure submission by the regulating authorities, thus delaying time to submission and licensure of;

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• failure to achieve a competitive value proposition in terms of product release specifications and our vein-to-vein delivery time;

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Due to this, we are at higher risk of supply disruptions to regional factors that could impair our supply chains.

Examples of this include an expanded conflict in Eastern Europe and severe volcanic activity in Iceland, either of which has the potential to disrupt international air traffic for weeks.

Even if a product candidate were to successfully obtain approval from the FDA, the European Commission or other comparable regulatory authorities in other jurisdictions, any approval might contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, or may be subject to burdensome post-approval study or risk management requirements.

Even though we have received FDA approval for AUCATZYL in r/r B-ALL, and even if any of our other product candidates were to successfully obtain approval from the FDA, the European Commission or other comparable regulatory authorities in other jurisdictions, any approval might contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, or may be subject to burdensome post-approval study or risk management requirements.

If we are unable to obtain regulatory approval for one of our product candidates in one or more jurisdictions, or any approval contains significant limitations, we may not be able to obtain sufficient funding to continue the development of that product or generate revenues attributable to that product candidate.

Also, any regulatory approval of our current or future product candidates, once obtained, may be withdrawn.

Also, the regulatory approval of AUCATZYL, or of any of our other current or future product candidates, once obtained, may be withdrawn.

See the risk factor titled “—Even if we complete the necessary preclinical studies and clinical trials, the regulatory approval process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some or all of our product candidates.

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However, we may not be able to develop product candidates that are safe and effective, or which compare favorably with our existing product candidates.

Even if we are successful in continuing to build our pipeline and developing next-generation product candidates or expanding into solid tumor indications or autoimmune diseases, the potential product candidates that we identify may not be suitable for clinical development, including as a result of lack of safety, lack of tolerability, lack of anti-tumor activity, or other characteristics that indicate that they are unlikely to be products that will receive marketing approval, achieve market acceptance or obtain reimbursements from third-party payors.

Even if we are successful in continuing to build our pipeline and developing next-generation product candidates or expanding into solid tumor indications or autoimmune diseases, the potential product candidates that we identify may not be suitable for clinical development, including as a result of lack of safety, lack of tolerability, lack of activity, or other characteristics that indicate that they are unlikely to be products that will receive marketing approval, achieve market acceptance or obtain reimbursements from third-party payors.

If we do not successfully develop and commercialize product candidates or collaborate with others to do so, we will not be able to obtain product revenue in future periods, which could significantly harm our financial position and adversely affect the trading price of our ADSs.

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Our preclinical programs may experience delays or may never advance to clinical trials, which would adversely affect our ability to obtain regulatory approvals or to commercialize these programs on a timely basis or at all, which would have an adverse effect on our business.

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We may experience difficulties in patient enrollment in our clinical trials for a variety of reasons.

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 study until its conclusion.

The enrollment of patients depends on many factors, including:

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• the size and nature of the patient population required for analysis of the trial’s primary and secondary endpoints;

• the proximity of patients to study sites;

• the proximity of patients to trial sites;

• the design of the clinical trial;

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• our ability to obtain and maintain patient consents;

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• disruptions to healthcare systems caused by global disease pandemics;

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For example, our clinical trial for AUTO4 seeks to enroll patients with peripheral T cell lymphoma, a rare and heterogeneous form of non-Hodgkin lymphoma (“NHL”).

Other companies are conducting clinical trials with their redirected T cell therapies in multiple myeloma, pediatric or adult relapsed or refractory acute B lymphoblastic leukemia (“B-ALL”), or pediatric or adult ALL, and relapsed or refractory DLBCL, relapsed or refractory MCL and seek to enroll patients in their studies that may otherwise be eligible for our clinical trials, which could lead to slow recruitment and delays in our clinical programs.

Other companies are conducting clinical trials with their redirected T cell therapies in multiple myeloma, pediatric or adult r/r B-ALL, or pediatric or adult ALL, and r/r DLBCL, r/r MCL and seek to enroll patients in their studies that may otherwise be eligible for our clinical trials, which could lead to slow recruitment and delays in our clinical programs.

In addition, since the number of qualified clinical investigators is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which could further reduce the number of patients who are available for our clinical trials in these clinical trial sites.

Moreover, because our product candidates represent a departure from more commonly used methods for cancer treatment and autoimmune diseases, potential study participants and their doctors may be inclined to use conventional therapies, such as chemotherapy and antibody therapy, rather than participate in our clinical trials.

Moreover, because our product candidates represent a departure from more commonly used methods for cancer treatment and autoimmune diseases, potential trial participants and their doctors may be inclined to use conventional therapies, such as chemotherapy and antibody therapy, rather than participate in our clinical trials.

Delays in patient enrollment may result in increased costs or may affect the timing or outcome of the planned clinical trials, which could prevent completion of these clinical trials and adversely affect our ability to advance the development of our product candidates.

In addition, many of the factors that may lead to a delay in the commencement or completion of clinical trials may also ultimately lead to the denial of regulatory approval of our product candidates.

The market opportunities for certain of our product candidates may be limited to those patients who are ineligible for or have failed prior treatments and may be small, and our projections regarding the size of the addressable market may be incorrect.

For instance, cancer therapies are sometimes characterized as first line, second line or later lines, and the FDA often approves new therapies initially only for later line use.

The market opportunities for our product candidates may be limited to those patients who are ineligible for or have failed prior treatments and may be small, and our projections regarding the size of the addressable market may be incorrect.

Cancer therapies are sometimes characterized as first line, second line or later lines, and the FDA often approves new therapies initially only for later line use.

When blood cancers are detected, they are treated with the first line of therapy with the intention of curing the cancer.

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Patients are generally referred to clinical trials in these situations.

We are currently developing obe-cel for treatment of relapsed / refractory adult patients with B-ALL.

As a next step, obe-cel could be developed in newly diagnosed patients with B-ALL as a consolidation strategy in first complete remission in order to replace or avoid allogeneic transplantation.

AUTO4 is currently being developed as a treatment option for relapsed / refractory TRBC1-positive T cell lymphoma patients.

If AUTO4 is eventually approved as a second line therapy, we may seek to initiate a trial to position it as a consolidation therapy after first line chemotherapy in T cell lymphoma.

There is no guarantee that any of our product candidates, even if approved in later lines, would be approved for an earlier line of therapy.

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Even if we obtain significant market share for our product candidates, because the potential target populations are small, we may never achieve significant revenues without obtaining regulatory approval for additional indications or as part of earlier lines of therapy.

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Adverse side effects or other safety risks associated with our product candidates could delay or preclude approval, cause us to suspend or discontinue clinical trials, cause us to abandon product candidates, limit the commercial profile of an approved label, or result in significant negative consequences following any potential marketing approval.

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The life-threatening events were related to cardiac dysfunction, kidney dysfunction and neurotoxicity.

Severe and life-threatening toxicities occurred mostly in the first two weeks after cell infusion and generally resolved within three - four weeks, but several patients died in clinical trials involving CAR T cells developed by other companies and academic institutions.

For example, at the ASH Annual Meeting in December 2023 we presented safety data from a pooled analysis of 127 patients treated in the FELIX trial, where we observed that 2% of patients, had equal to or greater than Grade 3 CRS and that 7% of patients, had equal to or greater than Grade 3 ICANS.

In addition, the FDA recently announced a requirement that approved BCMA-directed or CD19-directed autologous CAR T cell immunotherapies carry a boxed warning in their labeling for the risk of developing secondary T cell malignancies.

There can be no assurance that patients in ongoing or future trials of obe-cel, AUTO4 or any of our other product candidates will not experience more severe CRS, unacceptable levels of neurotoxicity or other serious adverse events.

Severe and life-threatening toxicities occurred mostly in the first two weeks after cell infusion and generally resolved within three to four weeks, but several patients died in clinical trials involving CAR T cells developed by other companies and academic institutions.

For example, the FDA-approved label for AUCATZYL carries a boxed warning for, among other adverse side effects, the risk of developing secondary T-cell malignancies.

There can be no assurance that patients in ongoing or future trials of obe-cel in additional indications, or any of our other product candidates will not experience more severe CRS, unacceptable levels of neurotoxicity or other serious adverse events.

Our clinical trials include cancer patients who are very sick and whose health is deteriorating, and we expect that additional clinical trials of our other product candidates will include similar patients with deteriorating health.

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We may not commercialize, market, promote or sell any product candidate without obtaining marketing approval from the FDA, the European Commission or other comparable regulatory authority, and we may never receive such approvals.

It is impossible to predict accurately when or if any of our product candidates will prove effective or safe in humans and will receive regulatory approval.

Although we have received FDA approval for AUCATZYL in r/r B-ALL, it is impossible to predict accurately when or if any of our other product candidates will prove effective or safe in humans and will receive regulatory approval.

Before obtaining marketing approval from regulatory authorities for the commercial sale of any of our product candidates, we must demonstrate through lengthy, complex and expensive preclinical testing and clinical trials that our product candidates are both safe and effective for use in each target indication.

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• we may decide, or regulators may require us, to conduct additional clinical trials or abandon product development programs;

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• the number of patients required for clinical trials of our product candidates may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate, participants may drop out of these clinical trials at a higher rate than we anticipate or we may fail to recruit suitable patients to participate in a trial;

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We may not be able to successfully create our own manufacturing infrastructure for supply of our, or our current or future collaborators', requirements of programmed T cell product candidates for use in clinical trials and for commercial sale.

Our manufacturing and commercialization strategy is based on establishing a fully integrated vein-to-vein product delivery cycle.

We have constructed and use a new facility (which we call “The Nucleus”) in Stevenage, UK which we believe will support our clinical manufacturing capacity and potential commercial manufacturing needs.

Our manufacturing and commercialization strategy is based on establishing a fully integrated vein-to-delivery cycle.

We have constructed and use a new facility (which we call “The Nucleus”) in Stevenage, U.K.

which we believe will support our commercial manufacturing needs for AUCATZYL and any future products.

Although we have received approval and licensure from health authorities to enter into operations at this facility, we may not be able to maintain ongoing licensure requirements.

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There are a small number of individuals with experience in cell therapy and the competition for these individuals is high.

We expect that the establishment of our own commercial cell manufacturing facilities will provide us with enhanced control of product supply for both clinical trials and the commercial market, enable the more rapid implementation of process changes, and allow for better long-term cost margins.

However, we have limited experience as a company in designing and operating a commercial cell therapy or vector manufacturing facility and may never be successful in developing our own manufacturing facility or capability.

We have limited experience as a company in designing and operating a commercial cell therapy or vector manufacturing facility and may not be successful in sustaining our own manufacturing capability.

We may establish additional manufacturing sites as we expand our commercial footprint to multiple geographies, which may lead to regulatory delays or prove costly.

Even if we are successful, our manufacturing operations could be affected by cost-overruns, unexpected delays, equipment failures, labor shortages, natural disasters, power failures and numerous other factors, or we may not be successful in establishing sufficient capacity to produce our product candidates in sufficient quantities to meet the requirements for the potential launch or to meet potential future demand, all of which could prevent us from realizing the intended benefits of our manufacturing strategy and have a material adverse effect on our business.

Our manufacturing operations could be affected by cost overruns, unexpected delays, equipment failures, labor shortages, natural disasters, power failures and numerous other factors, or we may not be successful in establishing sufficient capacity to produce our product candidates in sufficient quantities to meet the requirements for the potential launch or to meet potential future demand, all of which could prevent us from realizing the intended benefits of our manufacturing strategy and have a material adverse effect on our business.

We may not be successful in achieving cost of goods at commercial scale that provide for an attractive margin.

We believe that our current, enclosed manufacturing processes are fit for commercial scale and we anticipate they will enable commercial supply at an economical cost.

However, we have not yet established manufacturing capacity at commercial scale and may underestimate the cost and time required to do so, or overestimate cost reductions from economies of scale that can be realized with our manufacturing processes.

However, we have not yet sustained manufacturing capacity at commercial scale and may underestimate the cost and time required to do so, and may overestimate cost reductions from economies of scale that can be realized with our manufacturing processes.

We may ultimately be unable to manage the cost of goods for our product candidates to levels that will allow for a margin in line with our expectations and return on investment if and when those product candidates are commercialized.

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Our product candidates are biologics and the manufacture of our product candidates is complex and we may encounter difficulties in production, particularly with respect to process development or scaling-out of our manufacturing capabilities.

If we encounter such difficulties, our ability to provide supply of our product candidates for clinical trials or our products for patients, if approved, could be delayed or stopped.

Further, as we scale up our commercial production, we expect our margin will be lower as we will not initially be utilizing our full manufacturing capacity, which may cause our cost of goods to be higher until we reach economies of scale.

Our products and product candidates are biologics and the manufacture of such biologics is complex and we may encounter difficulties in production, particularly with respect to process development or scaling-out of our manufacturing capabilities.

If we encounter such difficulties, our ability to provide supply of our product candidates for clinical trials or our products for patients could be delayed or stopped.

We have developed a process for manufacturing programmed T cells in a fully enclosed system designed to minimize the risk of contamination, and we have improved the viral transduction process to help eliminate processing inconsistencies.

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While we have established a process which we believe is scalable for commercial production, each manufacturing process must be validated through the performance of process validation runs to guarantee that the facility, personnel, equipment, and process work as designed.

We have not yet manufactured or processed our product candidates on a commercial scale and may not be able to do so for any of our product candidates.

We have not yet manufactured or processed our product candidates on a commercial scale and may not be able to do so for any of our products or product candidates.

We, like other manufacturers of biologic products, may encounter difficulties in production, particularly in scaling up or out, validating the production process, and assuring high reliability of the manufacturing process.

These problems include delays or break-downs in logistics and shipping, difficulties with production costs and yields, quality control, and product testing, operator error, lack of availability of qualified personnel, as well as failure to comply with strictly enforced federal, state and foreign regulations, which are updated regularly.

Furthermore, if microbial, viral or other contaminants are discovered in our supply of product candidates or in the manufacturing facilities, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.

We cannot assure you that any of these or other issues relating to the manufacture of our product candidates will not occur in the future.

Furthermore, if microbial, viral or other contaminants are discovered in our supply of products or product candidates, or in the manufacturing facilities, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination.

We cannot assure you that any of these or other issues relating to the manufacture of our products or product candidates will not occur in the future.

Any delay or interruption in the supply of clinical trial supplies could delay the completion of clinical trials, increase the costs associated with maintaining clinical trial programs and, depending upon the period of delay, require us to begin new clinical trials at additional expense or terminate clinical trials completely.

The manufacture and delivery of programmed T cell therapies to patients involves complex, integrated processes, including harvesting T cells from patients, programming the T cells ex vivo , multiplying the T cells to obtain the desired dose, and ultimately infusing the T cells back into a patient’s body.

As a result of the complexities, the cost to manufacture biologics in general, and our programmed T cell product candidates in particular, is higher than traditional small molecule chemical compounds, and the manufacturing process is less reliable and is more difficult and costly to reproduce.

As a result of the complexities, the cost to manufacture biologics in general, and our programmed T cell products and product candidates in particular, is higher than traditional small molecule chemical compounds, and the manufacturing process is less reliable and is more difficult and costly to reproduce.

In addition, our manufacturing process will be susceptible to product loss or failure due to logistical issues associated with the collection of white blood cells from the patient, shipping such patient material to the manufacturing site, storing and processing such patient material, shipping the patient material with the programmed T cells back to the patient, and infusing the patient with the final product.

Other manufacturing issues include the differences in patient starting materials, inconsistency in cell growth, variability in product characteristics, interruptions in the manufacturing process, equipment or reagent failure, improper installation or operation of equipment, and vendor or operator error.

Any product that is out of specification, even if supplied to a treatment center for administration to a patient, must be provided free of charge.

Even minor deviations from normal manufacturing processes could result in reduced production yields, product defects, and other supply disruptions.

For example, in the FELIX clinical trial of obe-cel reported at the ASH Annual Meeting in December 2023, 7 patients out of the 153 patients enrolled on to the clinical trial did not receive an infusion of obe-cel due to manufacturing related reasons.

If we lose, destroy or otherwise impair the patient materials at any point in the vein-to-vein supply chain, the manufacturing process for that patient will need to be restarted and the resulting delay may adversely affect that patient’s outcome due to the risk of disease progression.

In addition, because our product candidates are manufactured for each particular patient, we will be required to maintain a chain of identity with respect to materials as they move from the patient to the manufacturing facility, through the manufacturing process, and back to the patient.

For example, in the FELIX clinical trial of obe-cel as published in the New England Journal of Medicine in December 2024, 7 patients out of the 153 patients enrolled on to the clinical trial did not receive an infusion of obe-cel due to manufacturing-related reasons.

If we lose, destroy or otherwise impair the patient materials at any point in the supply chain, the manufacturing process for that patient will need to be restarted, if sufficient starting materials are still available;

the resulting delay may adversely affect that patient’s outcome due to the risk of disease progression.

In addition, because our products and product candidates are manufactured for each particular patient, we will be required to maintain a chain of identity with respect to materials as they move from the patient to the manufacturing facility, through the manufacturing process, and back to the patient.

Maintaining such a chain of identity is difficult and complex, and failure to do so could result in adverse patient outcomes, loss of product, or regulatory action including withdrawal of our products from the market.

Further, as product candidates are developed through preclinical to late-stage clinical trials towards approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods, are altered along the way in an effort to optimize processes and results.

Such changes carry the risk that they will not achieve these intended objectives, and any of these changes could cause our product candidates to perform differently and affect the results of planned clinical trials or other future clinical trials.

Further, as product candidates are developed through preclinical to late-stage clinical trials towards approval and commercialization, changes may be considered in an effort to optimize processes or clinical approach.

Any changes to a process or clinical approach must serve the needs of the patient and delivery must be economically viable.

S uch changes carry the risk that they will not achieve these intended objectives, and any of these changes could cause our product candidates to perform differently and affect the results of planned clinical trials or other future clinical trials.

Our manufacturing facilities also require commissioning and validation activities to demonstrate that they operate as designed, and are subject to government inspections by the FDA, the MHRA, the competent authorities of EU Member States and other comparable regulatory authorities.

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Further, our facilities may fail to pass government inspections prior to or after the commercial launch of our product candidates, which would cause significant delays and additional costs required to remediate any deficiencies identified by the regulatory authorities.

Any of these challenges could delay completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our product candidate, impair commercialization efforts, increase our cost of goods, and have an adverse effect on our business, financial condition, results of operations and growth prospects.

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Any of these challenges could delay completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our product candidates, impair commercialization efforts of our products, increase our cost of goods, and have an adverse effect on our business, financial condition, results of operations and growth prospects.

Prior treatments can alter the patient's disease and negatively impact chances for achieving clinical activity with our programmed T cells.

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As a result, our programmed T cell product candidates may not recognize the cancer cell and may fail to achieve clinical activity.

Our most advanced product candidate, obe-cel, may face this challenge.

For example, ALL patients could have received currently approved therapies such as Blincyto or Kymriah or Tecartus, or a CD19 ADC, or a CD22 targeting CAR T, or CD22 ADC, like Besponsa, or similar products or product candidates prior to receiving obe-cel.

Similarly, patients with autoimmune diseases receive multiple types of treatment including toxic lympho-depleting chemotherapies, these may also have an impact of the viability of T cells collected from a patient and may also contribute to highly variable responses to programmed T cell therapies.

For example, patients with autoimmune diseases receive multiple types of treatment including toxic lympho-depleting chemotherapies, which may have an impact on the viability of T cells collected from a patient and may also contribute to highly variable responses to programmed T cell therapies.

If any of our product candidates do not achieve a sufficient level of clinical activity, we may discontinue the development of that product candidate, which could have an adverse effect on the value of our ADSs.

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Likewise, the MHRA has established the ILAP scheme to expedite the development and review of product candidates that show a potential to address to a significant extent an unmet medical need, based on early clinical data.

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We intend to seek breakthrough therapy designation, RMAT designation, ILAP or PRIME designation for some or all of our programmed T cell product candidates that may qualify.

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As a company based outside of the United States, our business is subject to economic, political, regulatory and other risks associated with international operations.

Our business is subject to risks associated with conducting business outside of the United States, as our company is based in the UK and conducts operations internationally.

Our business is subject to risks associated with conducting business outside of the United States, as our company is based in the U.K.

and conducts operations internationally.

Many of our suppliers and clinical trial relationships are located outside the United States.

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• difficulties in compliance with different, complex and changing laws, regulations and court systems of multiple jurisdictions and compliance with a wide variety of foreign laws, treaties and regulations;

• changes in non-U.S.

• changes in U.S.

regulations and customs, tariffs and trade barriers;

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dollar, euro and currency controls;

• changes in a specific country’s or region’s political or economic environment, including the implications of the UK's withdrawal from the EU;

• changes in a specific country’s or region’s political or economic environment, including the implications of the U.K.'s withdrawal from the EU;

• trade protection measures, import or export licensing requirements or other restrictive actions by governments;

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• workforce uncertainty in countries where labor unrest is more common than in the United States;

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• litigation or administrative actions resulting from claims against us by current or former employees or consultants individually or as part of class actions, including claims of wrongful terminations, discrimination, misclassification or other violations of labor law or other alleged conduct;

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• business interruptions resulting from geopolitical actions, including war and terrorism, natural disasters, including earthquakes, typhoons, floods and fires, or health epidemics, such as the coronavirus pandemic.

For example, the U.S.

government has threatened to impose new tariffs on imported products from various foreign countries.

As we produce our clinical and commercial supply of drug in the United Kingdom, the import of clinical and commercial supply of our products into the United States could be impacted to the extent any such tariffs are imposed and applicable to pharmaceutical products.

The impact of such tariffs would be subject to a number of factors, including the effective date and duration of such tariffs, changes in the amount, scope and nature of the tariffs in the future, any retaliatory responses to such actions that the target countries may take and any mitigating actions that may become available.

Tariffs on our products would increase our cost of importing clinical and commercial product into the United States, which would increase the cost of revenue from sale of therapies and reduce our margins on the sale of our products.

The United Kingdom’s withdrawal from the EU may have a negative effect on global economic conditions, financial markets and our business, which could reduce the price of our ordinary shares.

Following Brexit, the UK and the EU signed an EU-UK Trade and Cooperation Agreement (“TCA”), which became provisionally applicable on January 1, 2021 and entered into force on May 1, 2021.

This agreement provides details on how some aspects of the UK and EU’s relationship will operate going forwards however there are still uncertainties.

The TCA primarily focuses on ensuring free trade between the EU and the UK in relation to goods, including medicinal products.

Following Brexit, the U.K.

and the EU signed an EU-UK Trade and Cooperation Agreement (“TCA”), which became provisionally applicable on January 1, 2021 and entered into force on May 1, 2021.

The TCA primarily focuses on ensuring free trade between the EU and the U.K.

in relation to goods, including medicinal products.

Among the changes that have occurred are that Great Britain (England, Scotland and Wales) is treated as a “third country,” a country that is not a member of the EU and whose citizens do not enjoy the EU right to free movement.

Northern Ireland continues to follow many aspects of the EU regulatory rules, particularly in relation to trade in goods.

As part of the TCA, the EU and the UK recognize GMP inspections carried out by the other party and the acceptance of official GMP documents issued by the other party.

Northern Ireland continues to follow certain limited EU regulatory rules, including in relation to trade in medical devices, but not in relation to medicinal products.

As part of the TCA, the EU and the U.K.

recognize GMP inspections carried out by the other party and the acceptance of official GMP documents issued by the other party.

The TCA also encourages, although it does not oblige, the parties to consult one another on proposals to introduce significant changes to technical regulations or inspection procedures.

Among the areas of absence of mutual recognition are batch testing and batch release.

The UK has unilaterally agreed to accept EU batch testing and batch release.

has unilaterally agreed to accept EU batch testing and batch release.

However, the EU continues to apply EU laws that require batch testing and batch release to take place in the EU territory.

This means that medicinal products that are tested and released in the UK must be retested and re-released when entering the EU market for commercial use.

As it relates to marketing authorizations, Great Britain has a separate regulatory submission process, approval process and a separate national marketing authorization.

Northern Ireland continues, however, to be covered by the marketing authorizations granted by the European Commission.

For example, the scope of a marketing authorization for a medicinal product granted by the European Commission or by the competent authorities of EU Member States no longer encompasses Great Britain (England, Scotland and Wales).

In these circumstances, a separate marketing authorization granted by the UK competent authorities is required to place medicinal products on the market in Great Britain.

Northern Ireland continues, however, to be covered by the marketing authorizations granted by the European Commission.

On February 27, 2023, the UK Government and the European Commission reached a political agreement on the so-called “Windsor Framework”.

This means that medicinal products that are tested and released in the U.K.

must be retested and re-released when entering the EU market for commercial use.

On February 27, 2023, the U.K.

Government and the European Commission reached a political agreement on the so-called “Windsor Framework”.

The Framework is intended to revise the Northern Ireland Protocol to address some of the perceived shortcomings in its operation.

The agreement was adopted at the Withdrawal Agreement Joint Committee on March 24, 2023.

If the changes are adopted in the form proposed, medicinal products to be placed on the market in the UK will be authorized solely in accordance with UK laws.

Northern Ireland would be reintegrated back into a UK-only regulatory environment under the authority of the MHRA with respect to all medicinal products.

The implementation of the Windsor Framework would occur in stages, with new arrangements relating to the supply of medicinal products into Northern Ireland anticipated to take effect in 2025.

A significant proportion of the regulatory framework in the UK applicable to medicinal products is currently derived from EU Directives and Regulations.

The potential for UK legislation to diverge from EU legislation following Brexit could materially impact the regulatory regime with respect to the development, manufacture, import, approval, and commercialization of our product candidates in the UK or the EU.

Under the Windsor Framework, effective from January 1, 2025, medicinal products to be placed on the market in the U.K.

(including in Northern Ireland) will be authorized solely in accordance with U.K.

Northern Ireland is reintegrated back into a U.K.-only regulatory environment under the authority of the MHRA with respect to all medicinal products.

A significant proportion of the regulatory framework in the U.K.

applicable to medicinal products is currently derived from EU Directives and Regulations.

The potential for U.K.

legislation to diverge from EU legislation following Brexit could materially impact the regulatory regime with respect to the development, manufacture, import, approval, and commercialization of our product candidates in the U.K.

If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies governing clinical trials, our development plans may be impacted.

All of these changes could increase our costs and otherwise adversely affect our business.

Any delay in obtaining, or an inability to obtain, any regulatory approvals, as a result of Brexit or otherwise, would prevent us from commercializing our product candidates in the UK or the EU and restrict our ability to generate revenue and achieve and sustain profitability.

Any delay in obtaining, or an inability to obtain, any regulatory approvals, as a result of Brexit or otherwise, would prevent us from commercializing our product candidates in the U.K.

or the EU and restrict our ability to generate revenue and achieve and sustain profitability.

In addition, we may be required to pay taxes or duties or be subjected to other hurdles in connection with the importation of our product candidates into the EU.

If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the UK or the EU for our product candidates, or incur significant additional expenses to operate our business, which could significantly and materially harm or delay our ability to generate revenues or achieve profitability of our business.

If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the U.K.

or the EU for our product candidates, or incur significant additional expenses to operate our business, which could significantly and materially harm or delay our ability to generate revenues or achieve profitability of our business.

Any further changes in international trade, tariff and import/export regulations as a result of Brexit or otherwise may impose unexpected duty costs or other non-tariff barriers on us.

These developments, or the perception that any of them could occur, may significantly reduce global trade and, in particular, trade between the impacted nations and the UK.

These developments, or the perception that any of them could occur, may significantly reduce global trade and, in particular, trade between the impacted nations and the U.K.

It is also possible that Brexit may negatively affect our ability to attract and retain employees, particularly those from the EU.

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Exchange rate fluctuations may materially affect our results of operations and financial condition.

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Currently, we do not have any exchange rate hedging arrangements in place.

Additionally, although we are based in the UK, we source research and development, manufacturing, consulting and other services from the United States and other countries.

Additionally, although we are based in the U.K., we source research and development, manufacturing, consulting and other services from the United States and other countries.

Further, potential future revenue may be derived from the United States, countries within the euro zone, and various other countries around the world.

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We may experience economic loss and a negative impact on earnings or net assets solely as a result of currency exchange rate fluctuations.

We will need to manage the size of our organization, and we may experience difficulties.

As of December 31, 2023, we h ad 471 employees, 463 of whom are full-time.

As our development and commercialization plans and strategies develop, and as we further develop as a public co mpany, we may need additional managerial, operational, financial and other personnel, including personnel to support our product development and commercialization efforts.

We expect to continue to expand our development, commercial and regulatory capabilities and have recently developed sales, marketing and distribution capabilities, and as a result, we may encounter difficulties in managing our growth, which could disrupt our operations.

As of December 31, 2024, we had 650 employees, 647 of whom are full-time.

We expect to experience significant growth in the number of our employees and the scope of our operations, particularly as our development and commercialization plans and strategies develop, and as we further develop as a public company, we may need additional managerial, operational, financial and other personnel, including personnel to support our product development and commercialization efforts.

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

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Competition to hire from this limited candidate pool is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar personnel.

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We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions.

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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.

If our information technology systems or data, or those of third parties upon which we rely, are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to regulatory investigations or actions;

If our information technology systems or data, or those of third parties with whom we work, are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to regulatory investigations or actions;

fines and penalties;

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and other adverse consequences.

In the ordinary course of our business, we and the third parties upon which we rely, collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, process) personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, data we collect about trial participants in connection with clinical trials and sensitive third-party data (collectively, sensitive data).

As a result, we and the third parties upon which we rely face a variety of evolving threats, including but not limited to ransomware attacks, which could cause security incidents.

Cyber-attacks, malicious internet-based activity, online and offline fraud, and other similar activities threaten the confidentiality, integrity, and availability of our sensitive data and information technology systems, and those of the third parties upon which we rely.

In the ordinary course of our business, we and the third parties with whom we work, collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, process) personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, data we collect about trial participants in connection with clinical trials and sensitive third-party data (collectively, sensitive data).

As a result, we and the third parties with whom we work face a variety of evolving threats, including but not limited to ransomware attacks, which could cause security incidents.

Such threats are prevalent and continue to rise, are increasingly difficult to detect, and come from a variety of sources, including traditional computer “hackers,” threat actors, “hacktivists,” organized criminal threat actors, personnel (such as through theft or misuse), sophisticated nation states, and nation-state-supported actors.

Some actors now engage and are expected to continue to engage in cyber-attacks, including without limitation nation-state actors for geopolitical reasons and in conjunction with military conflicts and defense activities.

During times of war and other major conflicts, we, and the third parties upon which we rely, may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our products and services.

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We and the third parties upon which we rely are subject to a variety of evolving threats, including but not limited to social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, attacks enhanced or facilitated by artificial intelligence (“AI”), telecommunications failures, earthquakes, fires, floods, and other similar threats.

During times of war and other major conflicts, we, and the third parties with whom we work, may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our products and services.

We and the third parties with whom we work are subject to a variety of evolving threats, including but not limited to social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunctions, software or hardware failures, loss of data or other information technology assets, adware, attacks enhanced or facilitated by artificial intelligence (“AI”), telecommunications failures, earthquakes, fires, floods, and other similar threats.

In particular, severe ransomware attacks are becoming increasingly prevalent and can lead to significant interruptions in our operations (including our clinical trial activities), ability to provide our products or services, loss of sensitive data and income, reputational harm, and diversion of funds.

Extortion payments may alleviate the negative impact of a ransomware attack, but we may be unwilling or unable to make such payments due to, for example, applicable laws or regulations prohibiting such payments.

Remote work has become more common and has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers, and devices outside our premises or network, including working at home, while in transit and in public locations.

Remote work has increased risks to our information technology systems and data, as more of our employees utilize network connections, computers, and devices outside our premises or network, including working at home, while in transit and in public locations.

Additionally, future or past business transactions (such as acquisitions or integrations) could expose us to additional cybersecurity risks and vulnerabilities, as our systems could be negatively affected by vulnerabilities present in acquired or integrated entities’ systems and technologies.

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Our ability to monitor these third parties’ information security practices is limited, and these third parties may not have adequate information security measures in place.

If our third-party service providers experience a security incident or other interruption, we could experience adverse consequences.

While we may be entitled to damages if our third-party service providers fail to satisfy their privacy or security-related obligations to us, any award may be insufficient to cover our damages, or we may be unable to recover such award.

In addition, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties’ infrastructure in our supply chain or our third-party partners’ supply chains have not been compromised.

If the third parties with whom we work experience a security incident or other interruption, we could experience adverse consequences.

While we may be entitled to damages if the third parties with whom we work fail to satisfy their privacy or security-related obligations to us, any award may be insufficient to cover our damages, or we may be unable to recover such award.

In addition, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties’ infrastructure in our supply chain or that of the third parties with whom we work have not been compromised.

While we have implemented security measures designed to protect against security incidents, there can be no assurance that these measures will be effective.

We take steps designed to detect, mitigate, and remediate vulnerabilities in our information systems (such as our hardware and/or software, including that of third parties upon which we rely).

We may not, however, be able to detect and remediate all such vulnerabilities, including on a timely basis.

Further, we may experience delays in developing and deploying remedial measures and patches designed to address any such identified vulnerabilities.

We take steps designed to detect, mitigate, and remediate vulnerabilities in our information systems (such as our hardware and/or software, including that of third parties with whom we work).

We have not and may not in the future, however, detect and remediate all such vulnerabilities, including on a timely basis.

Further, we have (and may in the future) experienced delays in developing and deploying remedial measures and patches designed to address any such identified vulnerabilities.

Vulnerabilities could be exploited and result in a security incident.

Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive data or our information technology systems, or those of the third parties upon which we rely.

A security incident or other interruption could disrupt our ability (and that of third parties upon which we rely) to provide our products and services.

Certain of the previously identified or similar threats have in the past and may in the future cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive data or our information technology systems, or those of the third parties with whom we work.

For example, we have been the target of unsuccessful phishing attempts in the past, and expect such attempts will continue in the future.

For example, several of Snowflake’s customer accounts were targeted as part of Snowflake’s security incident in June 2024, and the Autolus customer account was among those targeted.

While Autolus did not experience any data loss or other material impact as a result of Snowflake incident, a security incident or other interruption could disrupt our ability (and that of third parties with whom we work) to provide our products and services.

We may expend significant resources or modify our business activities (including our clinical trial activities) to try to protect against security incidents.

Additionally, certain data privacy and security obligations may require us to implement and maintain specific security measures or industry-standard or reasonable security measures to protect our information technology systems and sensitive data.

Additionally, certain data privacy and security obligations require us to implement and maintain specific security measures or industry-standard or reasonable security measures to protect our information technology systems and sensitive data.

Applicable data privacy and security obligations may require us to notify relevant stakeholders, including affected individuals, customers, regulators, and investors, of security incidents or to implement other requirements, such as providing credit monitoring.

Such disclosures and compliance with such requirements are costly, and the disclosure or the failure to comply with such requirements could lead to adverse consequences.

If we (or a third party upon which we rely) experience a security incident or are perceived to have experienced a security incident, we may experience adverse consequences, such as government enforcement actions (for example, investigations, fines, penalties, audits, and inspections);

If we (or a third party with whom we work) experience a security incident or are perceived to have experienced a security incident, we may experience adverse consequences, such as government enforcement actions (for example, investigations, fines, penalties, audits, and inspections);

additional reporting requirements and/or oversight;

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Security incidents and attendant consequences may prevent or cause customers to stop using our products and services, deter new customers from using our products and services, and negatively impact our ability to grow and operate our business.

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Our contracts may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages, or claims related to our data privacy and security obligations.

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Additionally, sensitive data of ours could be leaked, disclosed, or revealed as a result of or in connection with our employees’, personnel’s, or vendors’ use of generative AI technologies.

We are subject to stringent and evolving U.S.

We and the third parties with whom we work are subject to stringent and evolving U.S.

and foreign laws, regulations and rules, contractual obligations, industry standards, policies and other obligations related to data privacy and security.

Our actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions;

Our (or the third parties with whom we work) actual or perceived failure to comply with such obligations could lead to regulatory investigations or actions;

litigation (including class claims) and mass arbitration demands;

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loss of revenue or profits;

loss of customers or sales;

and other adverse business consequences .

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Our data processing activities may subject us to numerous data privacy and security obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations relating to data privacy and security.

An increasing number of laws, regulations, and industry standards may govern data privacy and security.

For example, the EU GDPR and the UK GDPR impose strict requirements for processing personal data.

Outside of the U.S., an increasing number of laws, regulations, and industry standards govern data privacy and security.

For example, the EU GDPR and the U.K.

GDPR impose strict requirements for processing personal data.

Under the EU GDPR, companies may face temporary or definitive bans on data processing and other corrective actions;

fines of up to 20 million Euros under the EU GDPR, 17.5 million pounds sterling under the UK GDPR or, in each case, 4% of annual global revenue, whichever is greater;

fines of up to 20 million Euros under the EU GDPR, 17.5 million pounds sterling under the U.K.

GDPR or, in each case, 4% of annual global revenue, whichever is greater;

or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.

In addition, the processing of “special category personal data”, such as health information, may also impose heightened compliance burdens under the EU GDPR and the UK GDPR and is a topic of active interest among relevant regulators.

In addition, the processing of “special category personal data”, such as health information, may also impose heightened compliance burdens under the EU GDPR and the U.K.

GDPR and is a topic of active interest among relevant regulators.

The EU GDPR provides that European Economic Area (“EEA”) Member States may make their own further laws and regulations to introduce specific requirements related to the processing of “special categories of personal data”, including personal data related to health.

This fact may lead to greater divergence on the law that applies to the processing of such data types across the EEA and/or UK, compliance with which, as and where applicable, may increase our costs and could increase our overall compliance risk.

Such country-specific regulations could also limit our ability to collect, use and share data in the context of our EEA and/or UK operations, and/or could cause our compliance costs to increase, ultimately having an adverse impact on our business, and harming our business and financial condition.

This fact may lead to greater divergence on the law that applies to the processing of such data types across the EEA and/or U.K., compliance with which, as and where applicable, may increase our costs and could increase our overall compliance risk.

Such country-specific regulations could also limit our ability to collect, use and share data in the context of our EEA and/or U.K.

operations, and/or could cause our compliance costs to increase, ultimately having an adverse impact on our business, and harming our business and financial condition.

In the ordinary course of business, we transfer personal data from Europe and other jurisdictions to the United States.

Europe and other jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries.

In particular, the EEA, the UK, and Switzerland have significantly restricted the transfer of personal data to the United States and other countries whose privacy laws it believes are inadequate.

Other jurisdictions may adopt similarly stringent interpretations of their data localization and cross-border data transfer laws.

Although there are currently various mechanisms that may be used to transfer personal data from the EEA, the UK, and Switzerland to the United States in compliance with law, such as the EEA standard contractual clauses, the UK’s International Data Transfer Agreement/Addendum, the Swiss-U.S.

Data Privacy Framework (once officially recognized as a valid data transfer mechanism by the Swiss government), and the EU-U.S.

Data Privacy Framework and the UK Extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States.

If there is no lawful manner for us to transfer personal data from the EEA, the UK, Switzerland, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.

Additionally, companies that transfer personal data out of the EEA and UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators, individual litigants, and activist groups.

In particular, the EEA, the U.K., and Switzerland have significantly restricted the transfer of personal data to the United States and other countries whose privacy laws it believes are inadequate.

Other jurisdictions may adopt or have already adopted similarly stringent data localization and cross-border data transfer laws.

Although there are currently various mechanisms that may be used to transfer personal data from the EEA, the UK, and Switzerland to the United States in compliance with law, such as the EEA standard contractual clauses, the U.K.’s International Data Transfer Agreement/Addendum, the Swiss-U.S.

Data Privacy Framework, and the EU-U.S.

Data Privacy Framework and the U.K.

Extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States.

If there is no lawful manner for us to transfer personal data from the EEA, the U.K., Switzerland, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.

Additionally, companies that transfer personal data out of the EEA and U.K.

to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators, individual litigants, and activist groups.

Some European regulators have ordered certain companies to suspend or permanently cease certain transfers out of Europe for allegedly violating the EU GDPR’s cross-border data transfer limitations.

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In the United States, federal, state and local governments have enacted numerous data privacy and security laws, including data breach notification laws, data privacy laws, consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and other similar laws (e.g., wiretapping laws).

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Additionally, in the past few years, numerous U.S.

states—including California, Virginia, Colorado, Connecticut, and Utah—have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.

states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.

As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making.

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These state laws allow for statutory fines for noncompliance.

For example the CCPA provides fines of up to $7,500 per intentional violation and allows private litigants affected by certain data breaches to recover significant statutory damages.

Although the CCPA exempts some data processed in the context of clinical trials, the CCPA increases compliance costs and potential liability with respect to other personal data we maintain about California residents.

For example the CCPA provides fines and allows private litigants affected by certain data breaches to recover significant statutory damages.

Although the CCPA and other comprehensive U.S.

state privacy laws exempt some data processed in the context of clinical trials, these developments may further complicate compliance efforts and increases compliance costs and potential liability for us and the third parties with whom we work.

Similar laws are being considered in several other states, as well as at the federal and local levels, and we expect more states to pass similar laws in the future.

While these state laws, like the CCPA, also exempt some data processed in the context of clinical trials, these developments may further complicate compliance efforts, and increase legal risk and compliance costs for us and the third parties upon whom we rely.

In addition to data privacy and security laws, we are subject to industry standards adopted by industry groups and may become subject to such obligations in the future.

In addition to data privacy and security laws, we are contractually subject to industry standards adopted by industry groups and we are, and may become in the future, subject to such obligations.

We are also bound by other contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful.

We publish privacy policies, marketing materials, and other statements regarding data privacy and security.

If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.

We publish privacy policies, marketing materials, and other statements concerning data privacy and security.

Regulators in the United States are increasingly scrutinizing these statements, and if these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences.

Obligations related to data privacy and security (and consumers' data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty.

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We may at times fail (or be perceived to have failed) in our efforts to comply with our data privacy and security obligations.

Moreover, despite our efforts, our personnel or third parties upon whom we rely may fail to comply with such obligations, which could negatively impact our business operations.

If we or the third parties upon whom we rely fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to:

Moreover, despite our efforts, our personnel or third parties with whom we work may fail to comply with such obligations, which could negatively impact our business operations.

If we or the third parties with whom we work fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to:

government enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar);

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and imprisonment of company officials.

Our employees and personnel use generative AI technologies to perform their work, and the disclosure and use of personal data in generative AI technologies is subject to various privacy laws and other privacy obligations.

Governments have passed and are likely to pass additional laws regulating generative AI.

Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and lawsuits.

If we are unable to use generative AI, it could make our business less efficient and result in competitive disadvantages.

Any of these events could have a material adverse effect on our reputation, business, or financial condition, including but not limited to:

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Our ability to obtain clinical supplies of our product candidates could be disrupted if the operations of these suppliers are affected by a man-made or natural disaster or other business interruption.

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The global economy has experienced volatility and disruptions from the impacts of the international conflicts, terrorism and other geopolitical events, including the ongoing war in Ukraine and the current Israel-Hamas conflict in Gaza.

Although the length and impact of the ongoing military conflict is highly unpredictable, the war in Ukraine has led to market disruptions, including significant volatility in commodity prices, credit and capital markets, as well as supply chain interruptions, which contributed to record inflation globally.

In addition, global markets may experience additional disruptions as a result of the current Israel-Hamas conflict, with Israel having declared war on Hamas, a U.S.

designated Foreign Terrorist Organization, due to recent attacks.

In addition, global markets may experience additional disruptions as a result of political instability and tensions in the Middle East.

Although, to date, our business has not been materially impacted by the events described above, it is impossible to predict the extent to which our operations will be impacted in the short and long term, or the ways in which such matters may impact our business.

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As a public company with operations in the EU, we may be subject to the sustainability disclosure requirements set out in the EU Corporate Sustainability Reporting Directive.

A growing number of investors, regulators, self-regulatory organizations and other stakeholders have expressed an interest in Environmental, Social and Corporate Governance (“ESG”) matters, and are requiring more robust ESG disclosures.

The related legislative landscape in the EU has been evolving accordingly.

For example, EU Directive No 2464/2022 on Corporate Sustainability Reporting (“CSRD”) was adopted and entered into force on January 5, 2023, amending the current EU Accounting Directive No 2013/34.

The CSRD introduces new mandatory reporting obligations that will require the publication of audited sustainability information.

The CSRD is supplemented by EU Delegated Regulation No 2023/2772 which establishes the first set of European Sustainability Reporting Standards (“ESRS”), which are applicable to in-scope EU entities.

Further reporting standards are due to be adopted by June 2026, including for in-scope non-EU entities.

The CSRD and ESRS require certain mandatory disclosures, as well as disclosures of certain “material” sustainability matters in the company’s own operations, those of their subsidiaries and those of their value chain.

The identification of material sustainability matters requires a “double materiality” assessment.

This means that in-scope entities will have to assess both financial materiality, which are sustainability matters which generate risks or opportunities that affect, or could reasonably be expected to affect, the company’s financial position, financial performance, cash flows, access to finance or cost of capital over the short-, medium- or long-term, and impact materiality, which are the company’s material actual or potential, positive or negative impacts on people or the environment over the short-, medium- and long-term.).

Sustainability matters are material if they satisfy one or both of these materiality tests.

The CSRD applies to entities with securities admitted to trading on an EU regulated market, as well as large EU companies, EU parents of a “large group”, and to listed EU small or medium-sized enterprises, amongst others.

A number of investors, regulators, self-regulatory organizations and other stakeholders have expressed an interest in Environmental, Social and Corporate Governance (“ESG”) matters, and are requiring more robust ESG disclosures.

The related legislative landscape in the EU has been evolving rapidly.

For example, the EU adopted an ESG reporting rule, EU Directive No 2464/2022 on Corporate Sustainability Reporting (“CSRD”) that entered into force on January 5, 2023.

The CSRD introduces new mandatory reporting obligations for in-scope companies that require the publication of fulsome audited ESG disclosures, including disclosures under the EU Taxonomy Regulation 2020/852.

The CSRD currently applies to entities with securities admitted to trading on an EU regulated market, as well as large EU companies, EU parents of a “large group”, and to listed EU small or medium-sized enterprises, amongst others.

It will also apply to non-EU companies that have a certain threshold of EU-generated turnover and an in-scope EU subsidiary or EU branch meeting the turnover thresholds.

Companies subject to the CSRD are required to fulfil their reporting obligations in accordance with a staggered timeline depending on the category of company.

The first reports are expected in 2025 for the 2024 financial year, predominantly for entities with securities admitted to trading on an EU regulated market, and in 2026 for the 2025 financial year for many other EU companies (including EU subsidiaries of non-EU parents) that are not listed on an EU regulated market but meet the relevant size thresholds.

In response to new ESG initiatives and regulations we may voluntarily elect, or be required, to adopt strategies, policies, or procedures related to ESG matters and report on these.

Reporting on ESG goals and objectives may cause us to expend significant capital and human resources, and could divert management’s attention from central operational matters.

Reports could also lead to the disclosure of information that which may have a negative impact on our operations and reputation which may lead to additional exposure.

The first reports are being published during 2025 for the 2024 financial year, predominantly by entities with securities admitted to trading on an EU regulated market.

In February 2025, the EU proposed to delay the application of the CSRD and amend the thresholds and reporting requirements going forward.

The outcome of this proposal is currently uncertain, but it may impact Autolus Therapeutics plc’s ESG disclosure obligations in the EU.

In response to new ESG initiatives and regulations we may be required to adopt strategies, policies, or procedures related to ESG matters and report on these.

Reporting could involve capital and human resources and could lead to the disclosure of information that may have a negative impact on our operations and reputation which may lead to additional exposure.

Failure to accurately comply with any ESG reporting obligations may result in enforcement actions, sanctions, reputational harm or private litigation.

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We are dependent on intellectual property obtained or licensed from third parties, and if we were to fail to comply with our obligations under our existing and any future intellectual property licenses with third parties, we could lose intellectual property rights that are important to our business and we may not be able to continue developing or commercializing our product candidates, if approved.

We are party to an exclusive intellectual property license agreement with UCLB, the technology-transfer company of UCL, which is important to our business and under which we have acquired or licensed patent rights related to 17 patent families and other intellectual property related to our business.

We are party to an exclusive intellectual property license agreement with UCLB, the technology-transfer company of UCL, which is important to our business and under which we have acquired or licensed patent rights related to 17 p atent families and other intellectual property related to our business.

We expect to enter into additional license agreements in the future.

Our existing license agreement with UCLB imposes, and we expect that future license agreements will impose, various due diligence, milestone payment, royalty, insurance and other obligations on us.

Any uncured, material breach under the UCLB license agreement could result in our loss of rights to practice the patent rights (including those that have been assigned to us from UCLB) and other intellectual property licensed to us, and could compromise our development and commercialization efforts for our current or any future product candidates.

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Licensing of intellectual property is of critical importance to our business and involves complex legal, business and scientific issues.

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If disputes over intellectual property that we have licensed prevent or impair our ability to maintain our current licensing arrangement on acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates.

See the section of this Annual Report titled “Business - Our License Agreement with UCL Business Ltd.” for a more detailed description of our license agreement with UCLB, as well as our rights and obligations under the agreement.

We rely, and expect to continue to rely, on third parties to conduct the preclinical and clinical trials for our product candidates, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials or failing to comply with applicable regulatory requirements.

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Failure to do so by us or third parties can result in FDA or comparable foreign regulatory authority refusal to approve applications based on the clinical data, enforcement actions, adverse publicity and civil and criminal sanctions.

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Cell-based therapies rely on the availability of reagents, specialized equipment, and other specialty materials, which may not be available to us on acceptable terms or at all.

For some of these reagents, equipment, and materials, we rely or may rely on sole source vendors or a limited number of vendors, which could impair our ability to manufacture and supply our products.

Manufacturing our product candidates will require many reagents, which are substances used in our manufacturing processes to bring about chemical or biological reactions, and other specialty materials and equipment, some of which are manufactured or supplied by small companies with limited resources and experience to support commercial biologics production.

We currently depend on a limited number of vendors for access to facilities and supply of certain materials and equipment used in the manufacture of our product candidates.

For example, we currently use facilities and equipment at the Cell and Gene Therapy Catapult, as well as third party vendors, for vector and cell manufacturing.

In addition, we purchase equipment and reagents critical for the manufacture of our product candidates from Miltenyi and other suppliers on a purchase order basis.

Manufacturing our product and product candidates will require many reagents, which are substances used in our manufacturing processes to bring about chemical or biological reactions, and other specialty materials and equipment, some of which are manufactured or supplied by small companies with limited resources and experience to support commercial biologics production.

We currently depend on a limited number of vendors for access to facilities and supply of certain materials and equipment used in the manufacture of our product and product candidates.

For example, we currently use facilities and equipment at the Cell and Gene Therapy Catapult, as well as third party vendors, for vector and clinical cell manufacturing.

In addition, we purchase equipment and reagents critical for the manufacture of our product and product candidates from Miltenyi and other suppliers on a purchase order basis.

Some of our suppliers may not have the capacity to support commercial products manufactured under cGMP by biopharmaceutical firms or may otherwise be ill-equipped to support our needs.

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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 operate a manufacturing facility to manufacture materials for our CAR T product candidates, which requires significant resources.

A failure to successfully operate our manufacturing facility could lead to substantial delays and adversely affect our research and development efforts, including clinical trials, and the future commercial viability, if approved, of our CAR T product candidates.

We operate a manufacturing facility to manufacture materials for AUCATZYL and our product candidates, which requires significant resources.

A failure to successfully operate our manufacturing facility could lead to substantial delays and adversely affect our research and development efforts, including clinical trials, and commercial success of AUCATZYL and our product candidates, if approved.

We are also obligated to share some of the capabilities of the manufacturing facility with BioNTech under the BioNTech License Agreement.

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In some cases, the technical skills or technology required to manufacture our CAR T product candidates may be unique or proprietary and we may have difficulty transferring such skills or technology to another CMO and a feasible alternative may not exist.

If we fail to manufacture at our manufacturing facility, or obtain from a CMO, a sufficient supply of clinical materials for our clinical trials in accordance with applicable specifications on a timely basis, our research and development efforts, including clinical trials, the future commercial viability, if approved, of our CAR T product candidates, and our business, financial condition, results of operations and growth prospects could be materially adversely affected.

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We collaborate with third parties in the research, development and commercialization of certain of our product candidates.

If we fail to manufacture at our manufacturing facility, or obtain from a CMO, a sufficient supply of clinical materials for our clinical trials, or commercial materials for our commercial product in accordance with applicable specifications on a timely basis, our research and development efforts, including clinical trials, and the commercial success of our CAR T product, and product candidates, if approved, and our business, financial condition, results of operations and growth prospects could be materially adversely affected.

We, and the third parties on whom we rely in part for sales, marketing and distribution capabilities, may not be able to effectively market, sell and distribute AUCATZYL or our other product candidates, if approved.

We have invested, and expect to continue to invest, significant financial and management resources to develop internal our sales, distribution and marketing capabilities, particularly in anticipation of the commercial launch of AUCATZYL.

With respect to jurisdictions outside the US, we will need to commit resources to buildings these capabilities prior to any confirmation that obe-cel or our other product candidates will be approved in a territory.

We utilize a hybrid model that includes in-house and contracted resources in the United States and Europe, and we have engaged third parties and may engage additional third parties to provide these services.

We may enter into agreements with third parties to develop our commercial infrastructure for the commercial launch and continued sale of AUCATZYL and any product candidates that receive approval, including to potentially retain, train and deploy a direct sales force, but we have limited experience operating or managing a third-party sales force as a company.

There can be no assurance that the capabilities of the third parties will be more effective than an internally developed sales organization.

If third parties fail to hire, train, and retain qualified sales personnel, market our product successfully or on a cost-effective basis or otherwise terminates our relationship, our ability to generate revenue will be limited and we will need to identify and retain an alternative organization or develop our own sales and marketing capability.

This could involve significant delays and costs, including the diversion of our management’s attention from other activities.

We may also need to retain additional consultants or external service providers to assist us in sales, marketing and distribution functions, and may be unsuccessful in retaining such services on acceptable financial terms or at all.

There are risks involved with both establishing our own sales and marketing capabilities and entering into arrangements with third parties to perform these services.

For example, recruiting and training a commercial organization is expensive and time consuming and could delay any product launch.

If the commercial launch of a product candidate for which we recruit a sales force and establish marketing capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses.

This may be costly and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

Factors that may inhibit our efforts to commercialize our product candidates on our own include:

• the inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;

• the inability of sales personnel to obtain access to physicians or educate adequate numbers of physicians on the benefits of prescribing any future product that we may develop;

• the lack of complementary treatments 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.

If we enter into arrangements with third parties to perform sales, marketing and distribution services, our product revenue or the profitability to us from these revenue streams is likely to be lower than if we were to market and sell any product candidates that we develop ourselves.

In addition, we may not be successful in entering into arrangements with third parties to sell and market our product candidates or may be unable to do so on terms that are favorable to us.

We likely will have little control over such third parties and any of them may fail to devote the necessary resources and attention to sell and market our product candidates effectively.

If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we may not be successful in commercializing our product candidates.

We collaborate with third parties in the research, development and commercialization of certain of our product and product candidates.

If our collaborators do not perform as expected or if we are unable to maintain existing or establish additional collaborations, our ability to develop and commercialize our product candidates may be adversely affected.

We have collaboration and license agreements with, for example, BioNTech SE, Cabaletta Bio Inc., Moderna Inc., Bristol-Myers Squibb Company, and investee of Syncona Portfolio Limited.

We have collaboration and license agreements with, for example, BioNTech SE, Cabaletta Bio Inc., Moderna Inc., Bristol-Myers Squibb Company, and others.

These agreements provide us with important funding for our programs.

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In addition, any termination of an agreement by the relevant collaborators could affect our ability to develop further such product candidates or adversely affect how we are perceived in scientific and financial communities.

All of the risks relating to product development, regulatory approval and commercialization described in this Annual Report also apply to the activities of our program collaborators.

All of the risks we face relating to product development, regulatory approval and commercialization also apply to the activities of our program collaborators.

In our collaboration arrangements, we depend on the performance of our collaborators.

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If our collaborators terminate or breach our agreements with them, or otherwise fail to complete their obligations in a timely manner, it may have a detrimental effect on our financial position by reducing or eliminating the potential for us to receive technology access and license fees, milestones and royalties, reimbursement of development costs, as well as possibly requiring us to devote additional efforts and incur costs associated with pursuing internal development of product candidates.

Furthermore, if our collaborators do not prioritize and commit sufficient resources to our product candidates, we or our partners may be unable to develop or commercialize these product candidates, which would limit our ability to generate revenue and become profitable.

We do not and will not have access to all information regarding the product candidates we license to our collaboration partners.

Furthermore, if our collaborators do not prioritize and commit sufficient resources to our product or product candidates, we or our partners may be unable to develop or commercialize these products or product candidates, which would limit our ability to generate revenue and become profitable.

We do not and will not have access to all information regarding the product candidates we license to our collaborators.

Consequently, our ability to inform our shareholders about the status of such product candidates, and to make informed operational and investment decisions about the product candidates to which we have retained development and commercialization rights, may be limited.

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Any of these relationships may require us to incur non-recurring and other charges, increase our near and long-term expenditures, issue securities that dilute our existing shareholders or disrupt our management and business.

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We face significant competition in seeking appropriate collaborative partners.

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Risks Related to Regulatory Approval of Our Product Candidates and Other Legal Compliance Matters

Even if we complete the necessary preclinical studies and clinical trials, the regulatory approval process is expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some or all of our product candidates.

As a result, we cannot predict when or if, and in which territories, we will obtain marketing approval to commercialize a product candidate.

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Failure to obtain marketing approval for a product candidate will prevent us from commercializing the product candidate.

We have not received approval to market any of our product candidates from regulatory authorities in any jurisdiction.

We have only limited experience in filing and supporting the applications necessary to gain marketing approvals and may rely on third-party CROs, to assist us in this process.

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Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product not commercially viable.

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If we experience delays in obtaining approval or if we fail to obtain approval of our product candidates, the commercial prospects for our product candidates may be harmed and our ability to generate revenues will be impaired.

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We may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our products in any market.

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

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

Obtaining and maintaining regulatory approval of our product candidates in one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other jurisdiction, but a failure or delay in obtaining regulatory approval in one jurisdiction may have a negative effect on the regulatory approval process in others.

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

For example, even though the FDA granted marketing approval for AUCATZYL in the U.S.

for the treatment of r/r B-ALL, comparable regulatory authorities in other jurisdictions must also approve the manufacturing, marketing and promotion of AUCATZYL/obe-cel in those countries.

Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from those in the United States, including additional manufacturing quality controls, or additional preclinical studies or clinical trials, as clinical studies conducted in one jurisdiction may not be accepted by regulatory authorities in other jurisdictions.

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Obtaining foreign regulatory approvals and compliance with foreign regulatory requirements could result in significant delays, difficulties and costs for us and could delay or prevent the introduction of our products in certain countries.

If we fail to comply with the regulatory requirements in international markets and/or to receive applicable marketing approvals, our target market will be reduced and our ability to realize the full market potential of our product candidates will be harmed.

Even if we obtain marketing approvals for our product candidates, the terms of approvals and ongoing regulation of our products may limit how we manufacture and market our products and compliance with such requirements may involve substantial resources, which could materially impair our ability to generate revenue.

Even if marketing approval of a product candidate is granted, an approved product and its manufacturer and marketer are subject to ongoing review and extensive regulatory requirements for manufacturing processes, labeling, packaging, distribution, adverse event reporting, pharmacovigilance oversight, storage, advertising, promotion, sampling, and recordkeeping, including the potential requirements to implement a REMS program in the United States or comparable foreign strategies, or similar schemes in other countries, or to conduct costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product.

We must also comply with requirements concerning advertising and promotion for any of our product candidates for which we obtain marketing approval.

Even though we have obtained marketing approval by the FDA for AUCATZYL, the terms of approvals and ongoing regulation of AUCATZYL may limit how we manufacture and market AUCATZYL and compliance with such requirements may involve substantial resources, which could materially impair our ability to generate revenue.

Even though we have been granted marketing approval by the FDA for AUCATZYL, an approved product and its manufacturer and marketer are subject to ongoing review and extensive regulatory requirements for manufacturing processes, labeling, packaging, distribution, adverse event reporting, pharmacovigilance oversight, storage, advertising, promotion, sampling, and recordkeeping, including the potential requirements to implement a REMS program in the United States or comparable foreign strategies, or similar schemes in other countries, or to conduct costly post-marketing studies or clinical trials and surveillance to monitor the safety or efficacy of the product.

We must also comply with requirements concerning advertising and promotion for AUCATZYL/obe-cel and for any of our other product candidates for which we obtain marketing approval.

Promotional communications with respect to prescription drugs are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved labeling.

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We or our suppliers could be subject to periodic unannounced inspections by the FDA, the competent authorities of EU Member States, or other regulatory authorities to monitor and ensure compliance with cGMP.

Failure to comply with applicable regulations could result in sanctions being imposed on us, including shutdown of the third-party vendor or invalidation of drug product lots or processes, fines, injunctions, civil penalties, delays, suspension, variation or withdrawal of approvals, license revocation, seizures or recalls of product candidates or drugs, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products, if approved, and significantly harm our business, financial condition, results of operations and prospects.

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Accordingly, if we receive marketing approval for one or more of our product candidates, we and suppliers will continue to expend time, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance and quality control.

Failure to comply with applicable regulations could result in sanctions being imposed on us, including shutdown of the third-party vendor or invalidation of drug product lots or processes, fines, injunctions, civil penalties, delays, suspension, variation or withdrawal of approvals, license revocation, seizures or recalls of product candidates or drugs, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products, and product candidates, if approved, and significantly harm our business, financial condition, results of operations and prospects.

Accordingly, we and suppliers will continue to expend time, money and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance and quality control.

If we are not able to comply with post-approval regulatory requirements, we could have the marketing approvals for our products withdrawn by regulatory authorities and our ability to market any future products could be limited, which could adversely affect our ability to achieve or sustain profitability.

Thus, the cost of compliance with post-approval regulations may have a negative effect on our operating results and financial condition.

Any product candidate for which we obtain marketing approval could be subject to post-marketing restrictions or recall or withdrawal from the market, and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our product candidates, when and if any of them are approved.

AUCATZYL, and any other product candidate for which we obtain marketing approval, could be subject to post-marketing restrictions or recall or withdrawal from the market, and we may be subject to penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our product candidates, when and if any of them are approved.

The FDA and other federal and state agencies, including the U.S.

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• injunctions or the imposition of civil or criminal penalties.

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Non-compliance by us or any future collaborator with regulatory requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also result in significant financial penalties and reputational damage.

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If any of these events occurs, our ability to sell such product may be impaired, and we may incur substantial additional expense to comply with regulatory requirements, which could adversely affect our business, financial condition and results of operations.

Changes in funding for the FDA or comparable foreign regulatory authorities, the SEC, and other government agencies could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed or commercialized in a timely manner, or otherwise prevent those agencies or authorities from performing normal functions on which the operation of our business may rely, which could negatively impact our business.

The ability of the FDA to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and accept payment of user fees, and statutory, regulatory, and policy changes.

Average review times at the agency have fluctuated in recent years as a result.

In addition, government funding of the FDA and other government agencies on which our operations may rely are subject to the political process, which is inherently fluid and unpredictable.

Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.

For example, over the last several years, the U.S.

government has shut down several times and certain regulatory authorities, such as the FDA and the SEC, have had to furlough critical government employees and stop critical activities.

If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

Further, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations due to insufficient funding of the SEC and other government agencies or due to a government shutdown that affects the SEC.

Similar considerations are applicable in relation to foreign regulatory authorities.

Our employees, independent contractors, principal investigators, consultants, commercial partners and vendors may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements.

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It is not always possible to identify and deter employee and independent contractor misconduct, and any precautions we take to detect and prevent improper activities may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws.

If any such actions are instituted against us, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, disgorgement of profits, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, National Health Service in the UK, or other government supported healthcare in other jurisdictions, contractual damages, reputational harm, diminished profits and future earnings, additional reporting or oversight obligations if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with the law and curtailment or restructuring of our operations, any of which could adversely affect our ability to operate.

If any such actions are instituted against us, those actions could have a significant impact on our business, including the imposition of civil, criminal and administrative penalties, damages, monetary fines, disgorgement of profits, possible exclusion from participation in Medicare, Medicaid and other federal healthcare programs, National Health Service in the U.K., or other government supported healthcare in other jurisdictions, contractual damages, reputational harm, diminished profits and future earnings, additional reporting or oversight obligations if we become subject to a corporate integrity agreement or other agreement to resolve allegations of non-compliance with the law and curtailment or restructuring of our operations, any of which could adversely affect our ability to operate.

Our business operations and current and future relationships with healthcare professionals, principal investigators, consultants, customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-kickback, fraud and abuse, false claims, physician payment transparency, health information privacy and security and other healthcare laws and regulations, which could expose us to substantial penalties.

Healthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval.

Healthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any products or product candidates for which we obtain marketing approval.

Our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors may expose us to broadly applicable fraud and abuse and other healthcare laws, including, without limitation, the U.S.

federal Anti-Kickback Statute and the U.S.

federal False Claims Act, that may constrain the business or financial arrangements and relationships through which we sell, market and distribute any product candidates for which we obtain marketing approval, and foreign equivalents.

In addition, we may be subject to physician payment transparency laws and patient privacy and security regulation by the U.S.

federal False Claims Act, that may constrain the business or financial arrangements and relationships through which we sell, market and distribute any products or product candidates for which we obtain marketing approval, and foreign equivalents.

In addition, we will be subject to physician payment transparency laws and patient privacy and security regulation by the U.S.

federal government and by the states and foreign jurisdictions in which we conduct our business.

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The applicable federal, state and foreign healthcare laws that may affect our ability to operate include the following:

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federal Physician Payments Sunshine Act, created under Section 6002 of Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the “ACA”), and its implementing regulations, created annual reporting requirements for certain manufacturers of drugs, devices, biologicals and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions), to annually report to the CMS, information related to certain payments and “transfers of value” provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other health care professionals (such as physicians assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members;

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• analogous state laws and regulations and foreign laws, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers;

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and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts;

• similar healthcare laws and regulations in the EU and other jurisdictions, including reporting requirements detailing interactions with and payments to healthcare providers and laws governing the data privacy and security of certain protected information, such as the EU GDPR and UK GDPR, which imposes obligations and restrictions on the collection and use of personal data relating to individuals located in the EU and UK (including health data).

GDPR, which imposes obligations and restrictions on the collection and use of personal data relating to individuals located in the EU and U.K.

(including health data).

Outside the United States, interactions between pharmaceutical companies and health care professionals are also governed by strict laws, such as national anti-bribery laws of European countries, national sunshine rules, regulations, industry self-regulation codes of conduct and physicians’ codes of professional conduct.

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

Our product candidates are subject to government price controls in certain jurisdictions that may affect our revenue.

There has been heightened governmental scrutiny in the UK, United States, EU and other jurisdictions of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.

Our products and product candidates are subject to government price controls in certain jurisdictions that may affect our revenue.

There has been heightened governmental scrutiny in the U.K., United States, EU and other jurisdictions of pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics.

In the United States, such scrutiny has resulted in several recent Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.

For example, in the United States, at the federal level in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

In response to Biden’s executive order, on September 9, 2021, the HHS, released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue to advance these principles.

Further, on August 16, 2022, President Biden signed the IRA, into law, which among other things (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions will take effect progressively starting in fiscal year 2023.

On August 29, 2023, HHS announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges.

It is currently unclear how the IRA will be implemented but is likely to have a significant impact on the pharmaceutical industry.

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In response to the Biden administration’s October 2022 executive order, on February 14, 2023, HHS released a report outlining three new models for testing by the CMS Innovation Center which will be evaluated on their ability to lower the cost of drugs, promote accessibility, and improve quality of care.

It is unclear whether the models will be utilized in any health reform measures in the future.

Further, on December 7, 2023, the Biden administration announced an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act.

For example, in the United States, at the federal level on August 16, 2022, the Inflation Reduction Act was signed into law, which among other things (i) directed HHS to negotiate the price of certain high-expenditure, single-source biologics that have been on the market for at least 11 years covered under Medicare (the “Medicare Drug Price Negotiation Program”) and (ii) imposed rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions took effect progressively starting in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon reimbursement prices of the first ten drugs that were subject to price negotiations, although the Medicare Drug Price Negotiation Program is currently subject to legal challenges.

On January 17, 2025, HHS selected fifteen additional products covered under Part D for price negotiation in 2025.

Each year thereafter more Part B and Part D products will become subject to the Medicare Drug Price Negotiation Program.

Further, on December 7, 2023, an initiative to control the price of prescription drugs through the use of march-in rights under the Bayh-Dole Act was announced.

On December 8, 2023, the National Institute of Standards and Technology published for comment a Draft Interagency Guidance Framework for Considering the Exercise of March-In Rights which for the first time includes the price of a product as one factor an agency can use when deciding to exercise march-in rights.

While march-in rights have not previously been exercised, it is uncertain if that will continue under the new framework.

The current Trump administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, CMS and related agencies.

These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.

These actions may include, for example, directives to reduce agency workforce, rescinding a Biden administration executive order tasking the Center for Medicare and Medicaid Innovation (“CMMI”) to consider new payment and healthcare models to limit drug spending and eliminating the Biden administration’s executive order that directed HHS to establishing an AI task force and developing a strategic plan.

Additionally, in its June 2024 decision in Loper Bright Enterprises v.

Raimondo (“Loper Bright”), the U.S.

Supreme Court overturned the longstanding Chevron doctrine, under which courts were required to give deference to regulatory agencies’ reasonable interpretations of ambiguous federal statutes.

The Loper Bright decision could result in additional legal challenges to current regulations and guidance issued by federal agencies applicable to our operations, including those issued by the FDA.

Congress may introduce and ultimately pass health care related legislation that could impact the drug approval process and make changes to the Medicare Drug Price Negotiation Program created under the IRA.

At the state level, legislatures have increasingly enacted 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.

Outside of the United States, particularly in the UK and EU, the pricing of prescription pharmaceuticals is subject to governmental control by individual EU Member States.

We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the United States or abroad, particularly in light of the recent U.S.

presidential and Congressional elections.

We expect that additional state and federal health care reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for health care products and services, which could result in reduced demand for our development candidates or additional pricing pressures, or otherwise adversely impact our operations.

Outside of the United States, particularly in the U.K.

and EU, the pricing of prescription pharmaceuticals is subject to governmental control by individual EU Member States.

In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product.

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If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our business could be harmed.

Current and future legislation in the United States and other countries may affect the prices we may obtain for our product candidates and increase the difficulty and cost for us to commercialize our product candidates.

Current and future legislation in the United States and other countries may affect the prices we may obtain for our products and future candidates and increase the difficulty and cost for us to commercialize our product candidates.

In the United States and many other countries, rising healthcare costs have been a concern for governments, patients and the health insurance sector, which has resulted in a number of changes to laws and regulations, and may result in further legislative and regulatory action regarding the healthcare and health insurance systems that could affect our ability to profitably sell any product candidates for which we obtain marketing approval.

For example, the ACA was enacted in the United States in March 2010 with the stated goals of containing healthcare costs, improving quality and expanding access to healthcare, and includes measures to change healthcare delivery, increase the number of individuals with insurance, ensure access to certain basic healthcare services, and contain the rising cost of care.

There have been executive, judicial and Congressional challenges to certain aspects of the ACA.

While Congress has not passed repeal legislation, several bills affecting the implementation of certain taxes under the ACA have been signed into law.

The Tax Cuts and Jobs Act of 2017, includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate”.

Additionally, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminated the health insurer tax.

Further, the Bipartisan Budget Act of 2018, among other things, amended the ACA, effective January 1, 2019, to increase from 50% to 70% the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole”.

On June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress.

Further, the IRA, among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

There have been executive, judicial and Congressional challenges and amendments to certain aspects of the ACA.

For example, the IRA, among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

The IRA also eliminates the “donut hole” under the Medicare Part D program beginning in 2025 by significantly lowering the beneficiary maximum out-of-pocket cost and creating a new manufacturer discount program.

It is unclear how additional changes, other such litigation, and the healthcare reform measures of the Biden administration will impact the ACA and our business.

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In addition, other federal health reform measures have been proposed and adopted in the United States.

For example, as a result of the Budget Control Act of 2011, providers are subject to Medicare payment reductions of 2% per fiscal year until 2032 unless additional Congressional action is taken.

Further, the American Taxpayer Relief Act of 2012 reduced Medicare payments to several providers and increased the statute of limitations period for the government to recover overpayments from providers from three to five years.

The Medicare Access and CHIP Reauthorization Act of 2015 also introduced a quality payment program (“Quality Payment Program”), under which certain individual Medicare providers will be subject to certain incentives or penalties based on new program quality standards.

The Quality Payment Program provides clinicians with two ways to participate, including through the Advanced Alternative Payment Models (“APMs”), and the Merit-based Incentive Payment System (“MIPS”).

Under both APMs and MIPS, performance data collected each performance year will affect Medicare payments in later years, including potentially reducing payments.

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

In December 2021, Regulation No 2021/2282 on HTA amending Directive 2011/24/EU, was adopted in the EU.

This Regulation, which entered into force in January 2022 and will apply as of January 2025, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas.

The Regulation foresees a three-year transitional period and will permit EU Member States to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

In December 2021, Regulation No 2021/2282 on HTA, was adopted in the EU.

This Regulation, which entered into application on January 12, 2025 and has a phased implementation, is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas.

The Regulation permits EU Member States to use common HTA tools, methodologies, and procedures across the EU, working together in four main areas, including joint clinical assessment of the innovative health technologies with the most potential impact for patients, joint scientific consultations whereby developers can seek advice from HTA authorities, identification of emerging health technologies to identify promising technologies early, and continuing voluntary cooperation in other areas.

Individual EU Member States continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement.

In light of the fact that the United Kingdom has left the EU, Regulation No 2021/2282 on HTA will not apply in the United Kingdom.

However, the UK Medicines and Healthcare products Regulation Agency (“MHRA”) is working with UK HTA bodies and other national organizations, such as the Scottish Medicines Consortium (“SMC”), the National Institute for Health and Care Excellence (“NICE”), and the All-Wales Medicines Strategy Group, to introduce new pathways supporting innovative approaches to the safe, timely and efficient development of medicinal products.

Legislators, policymakers and healthcare insurance funds in the EU and the United Kingdom may continue to propose and implement cost-containing measures to keep healthcare costs down, particularly due to the financial strain that the COVID-19 pandemic placed on national healthcare systems of European countries.

These measures could include limitations on the prices we would be able to charge for product candidates that we may successfully develop and for which we may obtain regulatory approval or the level of reimbursement available for these products from governmental authorities or third-party payors.

Further, an increasing number of EU and other foreign countries use prices for medicinal products established in other countries as “reference prices” to help determine the price of the product in their own territory.

Consequently, a downward trend in prices of medicinal products in some countries could contribute to similar downward trends elsewhere.

Individual EU Member States will continue to be responsible for assessing non-clinical (e.g., economic, social, ethical) aspects of health technologies, and making decisions on pricing and reimbursement.

If we are unable to maintain favorable pricing and reimbursement status in EU Member States for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EU could be negatively affected.

The combination of healthcare cost containment measures, increased health insurance costs, reduction of the number of people with health insurance coverage, as well as future legislation and regulations focused on reducing healthcare costs by reducing the cost of or reimbursement and access to pharmaceutical products, may limit or delay our ability to generate revenue, attain profitability, or commercialize our products.

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As an example, the regulatory landscape related to clinical trials in the EU has evolved.

The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022.

The CTR permits trial sponsors to make a single submission to both the competent authority and an ethics committee in each EU Member State, leading to a single decision for each EU Member State.

The assessment procedure for the authorization of clinical trials has been harmonized as well, including a joint assessment of some elements of the application by all EU Member States in which the trial is to be conducted, and a separate assessment by each EU Member State with respect to specific requirements related to its own territory, including ethics rules.

Each EU Member State’s decision is communicated to the sponsor through a centralized EU portal, the Clinical Trial Information System, or CTIS.

The CTR provides a three-year transition period.

The extent to which ongoing clinical trials will be governed by the CTR varies.

For clinical trials in relation to which an application for approval was made on the basis of the Clinical Trials Directive before January 31, 2023, the CTD will continue to apply on a transitional basis until January 31, 2025.

By that date, all ongoing trials will become subject to the provisions of the CTR.

The CTR will apply to clinical trials from an earlier date if the related clinical trial application was made on the basis of the CTR or if the clinical trial has already transitioned to the CTR framework before January 31, 2025.

In addition, on April 26, 2023, the European Commission adopted a proposal for a new Directive and Regulation to revise the existing pharmaceutical legislation.

If adopted in the form proposed, the recent European Commission proposals to revise the existing EU laws governing authorization of medicinal products may result in a decrease in data and market exclusivity opportunities for our product candidates in the EU and make them open to generic or biosimilar competition earlier than is currently the case with a related reduction in reimbursement status.

The EU Clinical Trials Regulation (“CTR”), which was adopted in April 2014 and repeals the EU Clinical Trials Directive (“CTD”), became applicable on January 31, 2022.

The CTR allows trial sponsors to make a single submission to both the competent authority and an ethics committee in each EU Member State, leading to a single decision for each EU Member State.

The assessment procedure for the authorization of clinical trials has been harmonized as well, including a joint assessment by all EU Member States concerned, and a separate assessment by each EU Member State with respect to specific requirements related to its own territory, including ethics rules.

Each EU Member State’s decision is communicated to the sponsor through a centralized EU portal.

Once the clinical trial approved, clinical study development may proceed.

The CTR foresaw a three-year transition period that ended on January 31, 2025.

Since this date, all new or ongoing trials are subject to the provisions of the CTR.

Compliance with the CTR requirements by us and our third-party service providers, such as CROs, may impact our developments plans.

In light of the entry into application of the CTR on January 31, 2022, we may be required to transition clinical trials for which we have obtained regulatory approvals in accordance with the CTD to the regulatory framework of the CTR.

Transition of clinical trials governed by the CTD to the CTR was required for clinical trials which had at least one site active in the EU on January 30, 2025.

A transitioning application had to be submitted to the competent authorities of EU Member States through the Clinical Trials Information Systems and related regulatory approval obtained to continue the clinical trial past January 30, 2025.

This required financial, technical and human resources.

It is currently unclear to what extent the UK will seek to align its regulations with the EU in the future.

The UK regulatory framework in relation to clinical trials is derived from existing EU legislation (as implemented into UK law, through secondary legislation).

On January 17, 2022, the UK Medicines and Healthcare products Regulatory Agency, or MHRA, launched an eight-week consultation on reframing the UK legislation for clinical trials.

The UK Government published its response to the consultation on March 21, 2023 confirming that it would bring forward changes to the legislation and such changes were laid in parliament on December 12, 2024.

These resulting legislative amendments will, if implemented in their current form, bring the UK into closer alignment with the CTR.

Failure of the UK to closely align its regulations with the EU may have an effect on the cost of conducting clinical trials in the UK as opposed to other countries and/or make it harder to seek a marketing authorization for the Company's product candidates on the basis of clinical trials conducted in the United Kingdom.

In addition, on April 26, 2023, the European Commission adopted a proposal for a new Directive and Regulation to revise the existing pharmaceutical legislation and on April 10, 2024, the Parliament adopted its related position.

The proposed revisions remain to be agreed and adopted by the European Council.

Moreover, on December 1, 2024, a new European Commission took office.

The proposal could, therefore, still be subject to revisions.

If adopted in the form proposed, the recent European Commission proposals to revise the existing EU laws governing authorization of medicinal products may result in a number of changes to the regulatory framework governing medicinal products, including a decrease in data and market exclusivity opportunities for our product candidates in the EU and make them open to generic or biosimilar competition earlier than is currently the case with a related reduction in reimbursement status.

If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, our development plans may be impacted.

We are subject to the U.K.

Bribery Act, the FCPA, and other anti-corruption laws, as well as export control laws, import and customs laws, trade and economic sanctions laws and other laws governing our operations.

Our operations are subject to anti-corruption laws, including the UK Bribery Act, the FCPA, the U.S.

Our operations are subject to anti-corruption laws, including the U.K.

Bribery Act, the FCPA, the U.S.

domestic bribery statute contained in 18 U.S.C.

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Travel Act, and other anti-corruption laws that apply in countries where we do business.

The UK Bribery Act, the FCPA and these other laws generally prohibit us and our employees and intermediaries from authorizing, promising, offering, or providing, directly or indirectly, improper or prohibited payments, or anything else of value, to government officials or other persons to obtain or retain business or gain some other business advantage.

Bribery Act, the FCPA and these other laws generally prohibit us and our employees and intermediaries from authorizing, promising, offering, or providing, directly or indirectly, improper or prohibited payments, or anything else of value, to government officials or other persons to obtain or retain business or gain some other business advantage.

The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring us to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls.

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Under the UK Bribery Act, we may also be liable for failing to prevent a person associated with us from committing a bribery offense.

We and those acting on our behalf operate in a number of jurisdictions that pose a high risk of potential UK Bribery Act or FCPA violations, and we participate in collaborations and relationships with third parties whose corrupt or illegal activities could potentially subject us to liability under the UK Bribery Act, FCPA or local anticorruption laws, even if we do not explicitly authorize or have actual knowledge of such activities.

Under the U.K.

Bribery Act, we may also be liable for failing to prevent a person associated with us from committing a bribery offense.

We and those acting on our behalf operate in a number of jurisdictions that pose a high risk of potential U.K.

Bribery Act or FCPA violations, and we participate in collaborations and relationships with third parties whose corrupt or illegal activities could potentially subject us to liability under the U.K.

Bribery Act, FCPA or local anticorruption laws, even if we do not explicitly authorize or have actual knowledge of such activities.

In addition, we cannot predict the nature, scope or effect of future regulatory requirements to which our international operations might be subject or the manner in which existing laws might be administered or interpreted.

Compliance with the UK Bribery Act, the FCPA and these other laws is expensive and difficult, particularly in countries in which corruption is a recognized problem.

Compliance with the U.K.

Bribery Act, the FCPA and these other laws is expensive and difficult, particularly in countries in which corruption is a recognized problem.

In addition, anti-corruption laws present particular challenges in the pharmaceutical industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees are considered foreign officials.

We are also subject to other laws and regulations governing our international operations, including regulations administered by the governments of the United States and the UK, and authorities in the EU, including applicable export control regulations, economic sanctions and embargoes on certain countries and persons, anti-money laundering laws, import and customs requirements and currency exchange regulations, collectively referred to as the Trade Control laws.

There is no assurance that we will be completely effective in ensuring our compliance with all applicable anti-corruption laws, including the UK Bribery Act, the FCPA or other legal requirements, including Trade Control laws.

If we are not in compliance with the UK Bribery Act, the FCPA and other anti-corruption laws or Trade Control laws, we may be subject to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on our business, financial condition, results of operations and liquidity.

Likewise, any investigation of any potential violations of the UK Bribery Act, the FCPA, other anti-corruption laws or Trade Control laws by United States, UK or other authorities could also have an adverse impact on our reputation, our business, results of operations and financial condition.

We are also subject to other laws and regulations governing our international operations, including regulations administered by the governments of the United States and the U.K., and authorities in the EU, including applicable export control regulations, economic sanctions and embargoes on certain countries and persons, anti-money laundering laws, import and customs requirements and currency exchange regulations, collectively referred to as the Trade Control laws.

There is no assurance that we will be completely effective in ensuring our compliance with all applicable anti-corruption laws, including the U.K.

Bribery Act, the FCPA or other legal requirements, including Trade Control laws.

If we are not in compliance with the U.K.

Bribery Act, the FCPA and other anti-corruption laws or Trade Control laws, we may be subject to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on our business, financial condition, results of operations and liquidity.

Likewise, any investigation of any potential violations of the UK Bribery Act, the FCPA, other anti-corruption laws or Trade Control laws by United States, U.K.

or other authorities could also have an adverse impact on our reputation, our business, results of operations and financial condition.

Further, the failure to comply with laws governing international business practices may result in substantial civil and criminal penalties and suspension or debarment from government contracting.

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Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.

We have identified a material weakness in our internal control over financial reporting.

If our remediation of the material weakness is not effective or if we fail to develop and maintain effective internal control over financial reporting, our ability to produce timely and accurate financial information or comply with Section 404 of the Sarbanes-Oxley Act of 2002 could be impaired, which could have a material adverse effect on our business and the trading price of our ADSs.

We previously identified material weaknesses in our internal control over financial reporting.

If we experience additional material weaknesses or otherwise fail to maintain an effective system of internal controls in the future, we may not be able to accurately report our financial condition or results of operations.

As a public company, we are subject to the reporting requirements of the Exchange Act, as well as the requirements of the Sarbanes-Oxley Act of 2002, as amended (the “Sarbanes-Oxley Act”), and the listing standards of the Nasdaq Stock Market.

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It also requires management to perform an annual assessment of the effectiveness of our internal control over financial reporting and disclosure of any material weaknesses in such controls.

In connection with the audit of our financial statements for the year ended December 31, 2023, we have identified a material weakness in our internal control over financial reporting in connection with the historic misinterpretation and application of ASC 740 - Income Taxes , resulting in our UK small and medium enterprise (SME) tax credits being incorrectly presented in income tax benefit (expense).

Refer to Note 3, Restatement of Previously Issued Consolidated Financial Statements, in the Consolidated Financial Statements in Part II, Item 8 of this report for additional information.

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Any failure to remediate the identified material weakness, or to develop or maintain effective controls, or any difficulties encountered in the implementation or improvement of such controls, could harm our operating results or cause us to fail to meet our reporting obligations and may result in a restatement of our financial statements for prior periods, such as the restatement of our previously issued consolidated financial statements described in more detail in this Annual Report on Form 10-K.

In connection with the audit of our financial statements for the year ended December 31, 2023, we identified a material weakness in our internal control over financial reporting in connection with the historic misinterpretation and application of ASC 740, resulting in our U.K.

SME tax credits being incorrectly presented in income tax benefit (expense).

Refer to Note 3, Restatement of Previously Issued Consolidated Financial Statements, in the Consolidated Financial Statements in Part II, Item 8 of our Annual Report for additional information.

We have taken steps to remediate the material weakness by (i) enhancing the training provided to the individuals operating the income taxation controls and related financial reporting controls and (ii) improving the design of our controls related to the use of taxation subject matter experts in the determination of our U.K.

SME tax credits balances.

This material weakness was remediated at June 30, 2024, but there can be no assurance that we will not identify further control deficiencies in this area.

In addition, in connection with our review procedures for the three months ended March 31, 2024, we identified an additional material weakness due to an insufficiency of controls over complex accounting transactions.

The lack of controls did not allow us to identify, understand and evaluate the impact of certain key judgments that arose during the three months ended March 31, 2024 related to the BioNTech Agreements.

Our process, as designed, was inadequate to deal with the complexity of the accounting for the transaction and did not allow for an effective and timely evaluation of these matters and their impact on our financial statements.

We have taken steps to remediate the material weakness by (i) implementing structured project plans and project monitoring techniques;

(ii) the use of summary outputs allowing for earlier review of key judgements, estimates and other factors which impact the financial statements;

and (iii) enhancing our review process, and controls including building in more time to allow for its effective operation and iv) assessing resourcing needs and capabilities.

This material weakness was remediated at December 31, 2024, but there can be no assurance that we will not identify further control deficiencies in this area.

Any failure to remediate the identified material weakness, or to implement and maintain effective internal control over financial reporting also could adversely affect the results of management evaluations and, to the extent they are required in the future, attestations of our independent registered public accounting firm with respect to our internal control over financial reporting.

We can provide no assurance that the measures we are taking and plan to take in the future will remediate the material weakness identified in connection with the restatement described in this report, or that any additional material weaknesses or restatements of financial results will not arise in the future due to a failure to implement and maintain adequate internal control over financial reporting or circumvention of these controls.

We can provide no assurance that the measures we are taking and plan to take in the future will remediate the material weaknesses described above, or that any additional material weaknesses or restatements of financial results will not arise in the future due to a failure to implement and maintain adequate internal control over financial reporting or circumvention of these controls.

In addition, even if we are successful in strengthening our controls and procedures, in the future those controls and procedures may not be adequate to prevent or identify irregularities or errors or to facilitate the fair presentation of our financial statements.

We continue to evaluate steps to remediate the material weakness.

We continue to evaluate steps to remediate the material weakness identified.

Any failure to maintain effective internal control over financial reporting could adversely impact our ability to report our financial position and results from operations on a timely and accurate basis.

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In addition, if we are unable to continue to meet these requirements, we may not be able to remain listed on the Nasdaq Global Select Market.

Risks Related to the Commercialization of Our Product Candidates

If we are unable to establish sales, marketing and distribution capabilities for our product candidates, or enter into sales, marketing and distribution agreements with third parties, we may not be successful in commercializing our product candidates, if and when they are approved.

We currently plan to build our global commercialization capabilities internally so we are able to commercialize obe-cel or any other product candidate, subject to obtaining regulatory approval.

To achieve commercial success for any product candidate for which we may obtain marketing approval, we will need to build a sales and marketing organization and establish logistics and distribution processes to commercialize and deliver our product candidates to patients and healthcare providers.

The development of sales, marketing and distribution capabilities will require substantial resources, will be time-consuming and could delay any product launch.

However, we may not be successful in entering into arrangements with third parties to sell, market and distribute our product candidates or may be unable to do so on terms that are favorable to us, or if we are able to do so, that they would be effective and successful in commercializing our products.

Our product revenues and our profitability, if any, would likely to be lower than if we were to sell, market and distribute any product candidates that we develop ourselves.

In addition, we would have limited control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our product candidates effectively.

If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates in the United States or elsewhere.

We operate in a rapidly changing industry and face significant competition, which may result in others discovering, developing or commercializing products before or more successfully than we do.

The development and commercialization of new biopharmaceutical products is highly competitive and subject to rapid and significant technological advancements.

There are a number of large pharmaceutical and biotechnology companies that currently market and sell products or are pursuing the development of product candidates for the treatment of cancer.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies.

Potential competitors also include academic institutions, government agencies and other public and private research organizations.

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(“Gilead”), Bristol-Myers Squibb (“BMS”), Janssen Biotech Inc., Bluebird bio, Inc.

(“Bluebird bio”), Roche Holding AG, Seattle Genetics, and Amgen Inc.

We are developing our lead program, obe-cel, a CD19-targeting programmed T cell product candidate for the treatment of adult ALL.

Novartis, Gilead and BMS have received marketing approval for anti-CD19 CAR T cell therapies.

Gilead's therapy was approved for the treatment of adult ALL in October 2021.

Obe-cel is expected to compete directly with these companies and therapies.

In addition, some companies, such as Cellectis, Inc., Les Laboratoires Servier SAS and Allogene Therapeutics Inc., are pursuing allogenic T cell products that could compete with our programmed T cell product candidates.

In addition, our competitors with development-stage programs may obtain marketing approval from the FDA, the European Commission or other comparable regulatory authorities for their product candidates more rapidly than we do, and they could establish a strong market position before we are able to enter the market.

Many of our competitors, either alone or with their strategic collaborators, have substantially greater financial, technical and human resources than we do.

Mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated among a smaller number of our competitors.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical study sites and patient registration for clinical studies, as well as in acquiring technologies complementary to, or necessary for, our programs.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

Even if any of our product candidates receives marketing approval, it may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success.

Even if we obtain approvals from the FDA, the European Commission or other comparable regulatory authorities and are able to initiate commercialization of our clinical-stage product candidates or any other product candidates we develop, the product candidate may not achieve market acceptance among physicians, patients, hospitals, including pharmacy directors, and third-party payors and, ultimately, may not be commercially successful.

If these products do not achieve an adequate level of acceptance, we may not generate significant product revenue and may not become profitable.

FDA’s investigation into secondary malignancies associated with CAR T cell therapies and other similar actions could result in increased government regulation, unfavorable public perception and publicity, stricter labeling requirements for those product candidates that are approved, and a decrease in demand for any such product candidates.

The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including:

• the clinical indications for which our product candidates are approved;

• physicians, hospitals, cancer treatment centers, and patients considering our product candidates as a safe and effective treatment;

• hospitals and cancer treatment centers establishing the infrastructure required for the administration of redirected T cell therapies;

• the potential and perceived advantages of our product candidates over alternative treatments;

• the prevalence and severity of any side effects;

• product labeling or product insert requirements of the FDA, the European Commission or other regulatory authorities;

• limitations or warnings contained in the labeling approved by the FDA or the European Commission;

• the timing of market introduction of our product candidates as well as competitive products;

• the cost of treatment in relation to alternative treatments;

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• the amount of upfront costs or training required for physicians to administer our product candidates;

• the availability of coverage, adequate reimbursement, and pricing by third-party payors and government authorities;

• the willingness of patients to pay out-of-pocket in the absence of comprehensive coverage and adequate reimbursement by third-party payors and government authorities;

• relative convenience and ease of administration, including as compared to alternative treatments and competitive therapies;

• the effectiveness of our sales and marketing efforts and distribution support.

Our efforts to educate physicians, patients, third-party payors and others in the medical community on the benefits of our products, if approved, may require significant resources and may never be successful.

Such efforts may require more resources than are typically required due to the complexity and uniqueness of our product candidates.

Because we expect sales of our product candidates, if approved, to generate substantially all of our product revenue for the foreseeable future, the failure of our product candidates to find market acceptance would harm our business and could require us to seek additional financing.

If our product candidates are approved but fail to achieve market acceptance among physicians, patients, hospitals, cancer treatment centers or others in the medical community, we will not be able to generate significant revenue.

Coverage and adequate reimbursement may not be available for our current or any future product candidates, which could make it difficult for us to sell profitably, if approved.

Market acceptance and sales of any product candidates that we commercialize, if approved, will depend in part on the extent to which reimbursement for these products and related treatments will be available from third-party payors, including government health administration authorities, managed care organizations and private health insurers.

Third-party payors decide which therapies they will pay for and establish reimbursement levels.

Third-party payors in the United States often rely upon Medicare coverage policy and payment limitations in setting their own coverage and reimbursement policies.

However, decisions regarding the extent of coverage and amount of reimbursement to be provided for any product candidates that we develop will be made on a payor-by-payor basis.

One payor’s determination to provide coverage for a drug does not assure that other payors will also provide coverage for the drug.

Additionally, a third-party payor’s decision to provide coverage for a therapy does not imply that an adequate reimbursement rate will be approved.

We may incur significant costs to conduct expensive pharmaco-economic studies in order to demonstrate the medical necessity and cost-effectiveness of our product candidates, in addition to the costs required to obtain FDA approvals.

Our product candidates may not be considered medically necessary or cost-effective.

Patients who are prescribed treatments for their conditions and providers prescribing such services generally rely on third-party payors to reimburse all or part of the associated healthcare costs.

Therefore, coverage and adequate reimbursement is critical to new medical product acceptance.

A primary trend in the U.S.

healthcare industry and elsewhere is cost containment.

Third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications.

We cannot be sure that coverage and reimbursement will be available for any drug that we commercialize and, if reimbursement is available, what the level of reimbursement will be.

Even if favorable coverage and reimbursement status is attained for one or more product candidates for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Inadequate coverage and reimbursement may impact the demand for, or the price of, any drug for which we obtain marketing approval.

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Additionally, we are developing a proprietary diagnostic test for use with certain of our product candidates.

We will be required to obtain coverage and reimbursement for this test separate and apart from the coverage and reimbursement we seek for our product candidates, if approved.

Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.

We face an inherent risk of product liability exposure related to the testing of our product candidates in human clinical trials and will face an even greater risk if we commercially sell any products that we may develop.

If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we will incur substantial liabilities.

Regardless of merit or eventual outcome, liability claims may result in:

• reduced resources of our management to pursue our business strategy;

• decreased demand for any product candidates or products that we may develop;

• injury to our reputation and significant negative media attention;

• withdrawal of clinical trial participants;

• initiation of investigations by regulators;

• product recalls, withdrawals or labeling, marketing or promotional restrictions;

• significant costs to defend the resulting litigation;

• substantial monetary awards paid to clinical trial participants or patients;

• loss of revenue;

• the inability to commercialize any products that we may develop.

We currently hold £10.0 million in product liability insurance coverage in the aggregate, with a per incident limit of £10.0 million, which may not be adequate to cover all liabilities that we may incur.

We may need to increase our insurance coverage as we expand our clinical trials or if we commence commercialization of our product candidates.

Insurance coverage is increasingly expensive.

We may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise.

Risks Related to Our Intellectual Property

If we are unable to obtain and maintain patent protection for our T cell programming technologies and product candidates, or if the scope of the patent protection obtained is not sufficiently broad, our competitors could develop and commercialize technology and biologics similar or identical to ours, and our ability to successfully commercialize our technology and product candidates may be impaired.

Our success depends, in large part, on our ability to obtain and maintain patent protection in the United States, the EU, the UK and other countries with respect to our product candidates.

Our success depends, in large part, on our ability to obtain and maintain patent protection in the United States, the EU, the U.K.

and other countries with respect to our product candidates.

We seek to protect our proprietary position by filing patent applications related to our technology and product candidates in the major pharmaceutical markets, including the United States, major countries in Europe and Japan.

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Any of these outcomes could impair our ability to prevent competition from third parties.

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Prosecution of our owned and in-licensed patent portfolio is at an early stage for some of our patent families.

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In any of these types of proceedings, a court or other agency with jurisdiction may find our patents invalid and/or unenforceable.

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The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the United States and abroad.

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For example, we are aware of third-party U.S.

patents that claim technology related to obe-cel.

patents will expire between 2023 and 2025, and there are no counterpart patents in Europe or the rest of the world that extend beyond the earliest expected regulatory approval date of obe-cel.

If regulatory approval is received for obe-cel, unless we are able to obtain a license or licenses to the third-party U.S.

patents that may claim technology related to obe-cel.

patents will expire between 2025 and 2038.

There are no counterpart patents in Europe or the rest of the world that extend beyond the earliest expected regulatory approval date of obe-cel in those jurisdictions.

Unless we are able to obtain a license or licenses to the third-party U.S.

patent or patents on commercially reasonable terms or any applicable patent or patents are invalidated, held to be unenforceable, or deemed uninfringed by our activities.

As a result, the future commercial opportunity of obe-cel in the United States could be adversely impacted.

As a result, the future commercial opportunity of AUCATZYL in the United States could be adversely impacted.

Moreover, we may fail to identify relevant third party patents or patent applications, or we may incorrectly conclude that the claims of an issued patent are invalid or are not infringed by our activities.

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If we are unable to obtain such licenses on commercially reasonable terms, our business could be harmed.

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We may become involved in lawsuits to protect or enforce our intellectual property, which could be expensive, time-consuming and unsuccessful.

Competitors may infringe our patents, if issued, trademarks, copyrights or other intellectual property.

Competitors may infringe our patents, trademarks, copyrights or other intellectual property.

To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming and divert the time and attention of our management and scientific personnel.

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In addition, while it is our policy to require our employees and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, such employees and contractors may breach the agreement and claim the developed intellectual property as their own.

As of December 31, 2023, our patent portfolio is comprised of 81 patent families, of which 17 patent families originated from UCLB, the technology-transfer company of UCL, 3 patent families are in-licensed from Noile-Immune Biotech, Inc., and 61 patent families we own and have originated from our own research.

As of December 31, 2024, our patent portfolio was comprised of 83 patent families, of which 17 patent families originated from UCLB, the technology-transfer company of UCL, and 63 patent families we own and have originated from our own research.

Of the 17 live patent families that were originally in-licensed from UCL, 16 have been assigned to us.

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Moreover, a loss of key personnel or their work product could hamper or prevent our ability to commercialize our products.

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We may be subject to claims challenging the inventorship or ownership of our owned or in-licensed patent rights and other intellectual property.

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Even if we or our licensors are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

Any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business.

We expect to rely on trademarks as one means to distinguish any of our product candidates that are approved for marketing from the products of our competitors.

We have not yet selected trademarks for our product candidates.

Our existing trademarks and any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business.

We expect to rely on trademarks as one means to distinguish AUCATZYL from the products of competitors, and also expect to rely in the future trademarks to protect any of our other product candidates that are approved for marketing.

We have a U.S.

trademark for AUCATZYL but we have not yet selected trademarks for our other product candidates, including obe-cel for r/r B-ALL in other jurisdictions.

For each selected trademark, we will need to apply to register them and our trademark applications may not be approved.

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Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, even in jurisdictions where we do pursue patent protection or from selling or importing products made using our inventions in and into the United States or other jurisdictions.

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Competitors may use our technologies in jurisdictions where we have not pursued and obtained patent protection to develop their own products and, further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States.

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The trading price of our ADSs has been and may continue to be highly volatile and may fluctuate due to factors beyond our control.

The trading price of our ADSs continues to be volatile.

The trading price of our ADSs has been volatile.

The stock market in general, and the market for biopharmaceutical and pharmaceutical companies in particular, has experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies.

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As a result of this volatility, you may not be able to sell your ADSs at or above the price paid for the ADSs.

In addition to the factors discussed in this “Risk Factors” section and elsewhere in this Annual Report, the trading price for our ADSs may be influenced by the following:

• the commencement, enrollment or results of our planned or future clinical trials of obe-cel and any other product candidates;

In addition to the factors discussed in this “Risk Factors” section and elsewhere in this report, the trading price for our ADSs may be influenced by the following:

• our failure to successfully execute our commercialization strategy with respect to AUCATZYL ;

• actions or announcements by third-party or government payors with respect to coverage and reimbursement of AUCATZYL ;

• the commencement, enrollment or results of our planned or future clinical trials our product candidates;

• the clinical or commercial success of competitive drugs, therapies or technologies;

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• the loss of any of our key scientific or management personnel;

• regulatory or legal developments in the United States, UK and other countries;

• regulatory or legal developments in the US, U.K.

and other countries;

• adverse actions taken by regulatory agencies with respect to our clinical trials or manufacturers;

• changes or developments in laws or regulations applicable to our product candidates and preclinical program;

• changes or developments in laws or regulations applicable to our product candidates and preclinical programs;

• changes to our relationships with collaborators, manufacturers or suppliers;

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• concerns regarding the safety of our product candidates or programmed T cells in general;

• concerns regarding the safety of AUCATZYL or our product candidates or programmed T cells in general;

• announcements concerning our competitors or the pharmaceutical industry in general;

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• sales of our ADSs or ordinary shares by us, members of our senior management and directors or our shareholders or the anticipation that such sales may occur in the future;

• general economic, political, and market conditions and overall fluctuations in the financial markets in the United States or the UK;

• price and volume fluctuations of the listed securities comparable companies and, in particular, those that operate in the biopharmaceutical industry;

• general economic, political, and market conditions and overall fluctuations in the financial markets in the United States or the U.K.;

• price and volume fluctuations of the listed securities of comparable companies and, in particular, those that operate in the biopharmaceutical industry;

• investors’ general perception of us and our business;

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Future sales of our ADSs in the public market could cause our share price to decline, even if our business is doing well.

As of March 20, 2024, approximately 265.8 million of our ordinary shares (including ordinary shares in the form of ADSs) were issued and outstanding.

Sales of a substantial number of shares of our ADSs in the public market, or the perception that these sales might occur, could depress the market price of our ADSs and could impair our ability to raise capital through the sale of additional equity securities.

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For example, in February 2024, we sold ADSs representing 58.3 million ordinary shares in an underwritten offering resulting in gross proceeds of $350.0 million, and we also sold ADSs representing 33.3 million ordinary shares to BioNTech in a private placement, resulting in gross proceeds of $200.0 million.

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We are contractually obligated to file a resale registration statement, on form S-3, to register the ADSs we sold to BioNTech in February 2024.

Upon the effectiveness of that registration statement, those ADSs will be freely tradeable.

We filed a resale registration statement on Form S-3 to register the ADSs we sold to BioNTech in February 2024.

Additionally, in 2022, we filed two “resale” registration statements on Form F-3 under the Securities Act to register a total of approximately 33.4 million of our ordinary shares, or securities convertible into our ordinary shares, held by certain of our investors, allowing these shares or ADSs to be sold in the public market.

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These restrictions may have an adverse effect on the value of the ADSs.

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Because we do not anticipate paying any cash dividends on our ADSs in the foreseeable future, capital appreciation, if any, will be our ADS holders’ and shareholders’ sole source of gains and they may never receive a return on their investment.

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In addition, for purposes of the above calculations, a non-U.S.

corporation that directly or indirectly owns at least 25% by value of the shares of another corporation is treated as if it held its proportionate share of the assets and received directly its proportionate share of the income of such other corporation.

corporation that directly or indirectly owns at least 25% by value of the shares of another corporation is treated as if it held its proportionate share of the assets and directly received its proportionate share of the income of such other corporation.

If we are a PFIC for any taxable year during which a U.S.

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Holders should consult their tax advisors regarding the potential application of these rules to their investment in our ADSs.

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Future changes to tax laws could materially adversely affect our company and reduce net returns to our shareholders.

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We are unable to predict what tax reform may be proposed or enacted in the future or what effect such changes would have on our business, but such changes, to the extent they are brought into tax legislation, regulations, policies or practices, could affect our financial position and overall or effective tax rates in the future in countries where we have operations, reduce post-tax returns to our shareholders, and increase the complexity, burden and cost of tax compliance.

The IRA enacted in the United States introduced, among other changes, a 15% corporate minimum tax on certain United States corporations and a 1% excise tax on certain stock redemptions by United States corporations (which the U.S.

Treasury indicated may also apply to certain stock redemptions by a foreign corporation funded (or deemed funded) by certain United States affiliates.

In addition, effective in 2022, the Tax Cuts and Jobs Act of 2017 eliminates the option to deduct research and development expenditures in the current period and requires taxpayers to capitalize and amortize them over five or fifteen years pursuant to Internal Revenue Code Section 174.

Tax authorities may disagree with our positions and conclusions regarding certain tax positions, or may apply existing rules in an unforeseen manner, resulting in unanticipated costs, taxes or non-realization of expected benefits.

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Contesting such an assessment may be lengthy and costly and if we were unsuccessful in disputing the assessment, the implications could increase our anticipated effective tax rate, where applicable.

We may be unable to use net operating loss and tax credit carryforwards and certain built-in losses to reduce future tax payments or benefits from favorable UK tax legislation.

As a UK resident trading entity, we are subject to UK corporate taxation.

We may be unable to use net operating loss and tax credit carryforwards and certain built-in losses to reduce future tax payments or benefits from favorable U.K.

tax legislation.

resident trading entity, we are subject to U.K.

corporate taxation.

Due to the nature of our business, we have generated losses since inception.

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Subject to any relevant utilization criteria and restrictions (including those that limit the percentage of profits that can be reduced by carried forward losses and those that can restrict the use of carried forward losses where there is a change of ownership of more than half the ordinary shares of the company and a major change in the nature, conduct or scale of the trade), we expect these to be eligible for carry forward and utilization against future operating profits.

Research and development expenditure is presented net of reimbursements from reimbursable tax and expenditure credits from the UK government.

As a company that carries out extensive research and development activities, we benefit from the UK research and development tax credit regime under the scheme for small or medium-sized enterprises, or SMEs, and also claim a Research and Development Expenditure Credit, or RDEC, to the extent that our projects are grant funded.

The SME Program has been particularly beneficial to us, as under such program the trading losses that arise from our qualifying R&D activities can be surrendered for a cash rebate of up to 33.35% of qualifying expenditure incurred prior to April 1, 2023 and decreasing to 18.6% after April 1, 2023.

Additionally, the U.K Government enacted further changes to the SME regime on March 4, 2024 which include the introduction of a new rate for R&D intensive companies of 27% (which we may qualify for) and comes into effect for expenditures incurred after April 1, 2024.

Qualifying expenditures largely comprise employment costs for research staff, consumables, outsourced contract research organization costs and utilities costs incurred as part of research projects for which we do not receive income.

A large proportion of costs in relation to our pipeline research, clinical trials management and manufacturing development activities, all of which are being carried out by our subsidiary Autolus Limited, are eligible for inclusion within these tax credit cash rebate claims.

Under the RDEC Program, tax credits for qualifying R&D expenditure incurred prior to April 1, 2023 are granted at a headline rate of 13% and can generate cash rebates of up to 10.5% of qualifying R&D expenditure.

The headline rate of RDEC increased to 20% on April 1, 2023 and can generate cash rebates of up to 15% on qualifying R&D expenditure incurred from this date.

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Amendments to the current SME and RDEC programs that are contained in the Finance Bill currently proceeding through the UK Parliament will take effect from periods on or after April 1, 2024 and will (i) (unless limited exceptions apply) introduce restrictions on the tax relief that can be claimed for expenditure incurred on sub-contracted R&D activities or externally provided workers, where such sub-contracted activities are not carried out in the UK or such workers are not subject to UK payroll taxes, and (ii) merge the SME Program and the RDEC Program into a single scheme which would generate net cash benefit of up to 15% of the qualifying expenditure for profit making companies and up to 16.2% for loss making companies.

We currently meet the conditions of the SME regime, but also can make claims under the RDEC regime to the extent that our projects are grant funded.

In addition, it is also expected that we will meet the conditions of the R&D intensive scheme and would be able to make claims under merged SME R&D intensive regime.

We may not be able to continue in the future to qualify as a small or medium-sized enterprise under the SME program, based on size criteria concerning employee headcount, turnover and gross assets.

If we cease to qualify under the SME regime, we may make a claim under the RDEC regime for periods ending December 31, 2024 or the merged R&D regime from period ending December 31, 2025.

It should be noted, however, that the types of qualifying expenditure in respect of which we may make claims under the RDEC regime are more restricted than under the SME regime (for example, it may be the case that certain subcontracted costs in respect of which claims may be made under the SME regime do not qualify for relief under the RDEC regime).

We may benefit in the future from the UK’s “patent box” regime, which allows certain profits attributable to revenues from patented products (and other qualifying income) to be taxed at an effective rate of 10% by giving an additional tax deduction.

Research and development, or R&D, expenditure is presented net of reimbursements from reimbursable tax and expenditure credits from the U.K.

As a company that carries out extensive R&D activities, we benefit from the U.K.

R&D tax credit regime.

In respect of our accounting period commencing January 1, 2024, we expect to qualify as a Small and Medium-sized Enterprise, or SME, that is not “R&D-intensive” for the purposes of the U.K.

R&D tax credit regime.

We may therefore surrender trading losses that arise from our R&D activities during the accounting period for a cash rebate of up to 18.6% of qualifying R&D expenditure.

We do not expect to qualify as a SME for R&D purposes for subsequent accounting periods due to exceeding the relevant headcount limits, and will therefore be entitled to make claims solely under the R&D expenditure credit, or RDEC, scheme, under which we will be able to receive cash payments or other tax relief at a lower rate (up to 16.2%).

R&D tax credit regime’s rules are complex, and if a tax authority were to challenge or seek to disallow our claims (in whole or in part, whether under RDEC or otherwise), for example by asserting that we do not (or the relevant expenditure does not) meet the technical conditions to be granted tax credits (or cash rebates), then a successful challenge or disallowance could have a material impact on our cash-flow and financial performance.

In addition, future changes to the U.K.

R&D tax credit regime (including changes in HMRC practice in respect of such regime) may mean that we no longer qualify or have a material impact on the extent to which we can make claims (or benefit from them).

We may also benefit in the future, when we generate profits subject to U.K.

corporate taxation, from the U.K.’s “Patent Box” regime, which allows certain profits attributable to revenues from patented products (and other qualifying income) to be taxed at an effective rate of 10% by giving an additional tax deduction.

We are the exclusive licensee or owner of one patent and several patent applications which, if issued, would cover our product candidates, and accordingly, future upfront fees, milestone fees, product revenues and royalties could be eligible for this deduction.

When taken in combination with the enhanced relief available on R&D expenditures, we expect a long-term rate of corporation tax lower than statutory to apply to us.

If, however, there are unexpected adverse changes to the UK R&D tax credit regime or the “patent box” regime, or for any reason we are unable to qualify for such advantageous tax legislation, or we are unable to use net operating loss and tax credit carryforwards and certain built-in losses to reduce future tax payments then our business, results of operations and financial condition may be adversely affected.

If, however, there are unexpected adverse changes to the U.K.

R&D tax credit regime or the “patent box” regime, or for any reason we are unable to qualify for such advantageous tax legislation, or we are unable to use net operating loss and tax credit carryforwards and certain built-in losses to reduce future tax payments then our business, results of operations and financial condition may be adversely affected.

This may impact our ongoing requirement for investment and the timeframes within which additional investment is required.

To date, Autolus Limited has recovered all of the VAT incurred on its expenditure in the UK on the basis of having an intention to solely make taxable supplies.

In recent months we have been working with our advisers in relation to the appropriate VAT treatment that should be applied in the UK in relation to Autolus Limited's primary income stream.

Our advisors are still finalizing their understanding of the full facts which underpin our CAR T therapy and will provide a more conclusive VAT opinion in due course but it has been mentioned during initial discussion that some products which include human blood can be exempt from a UK VAT perspective.

If the conclusion is that this activity is exempt from a UK VAT perspective, this may result in a retrospective restriction in terms of VAT recovered on a proportion of our UK expenditure (with this restriction likely being based on the UK market turnover as a percentage of global turnover).

We currently expect revenue from UK customers to only represent a small proportion of our overall activity.

We have been advised by HMRC that the sale of our obe-cel CAR T therapy to U.K.

customers in the future will be considered an exempt supply from a U.K.

VAT perspective.

Consequently, Autolus Limited has reassessed and commenced restricting the amount of U.K.

VAT it reclaims.

The restriction is based on an estimate of our U.K.

market turnover as a percentage of global turnover.

We currently expect revenue from U.K.

customers to only represent a small proportion of our overall activity.

If the proportion of revenue from U.K.

customers increases this would further restrict the amount of U.K.

input VAT which we are able to recover.

We have incurred, and will continue to incur, significant costs and demands upon management as a result of being a public company, and our management have devoted, and will continue to devote, substantial time to existing and new compliance initiatives.

As a public company listed in the United States, we incur significant legal, accounting and other expenses.

These expenses will likely become even more significant now that we no longer qualify as an emerging growth company under SEC rules effective as of December 31, 2023.

These expenses will likely become even more significant now that we no longer qualify as an emerging growth company under SEC rules.

The Sarbanes-Oxley Act, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of Nasdaq and other applicable securities rules and regulations impose various requirements on public companies in the United States, including the establishment and maintenance of effective disclosure and financial controls and corporate governance practices.

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This allows us to follow certain corporate governance practices that differ in significant respects from the corporate governance requirements applicable to domestic issuers listed on Nasdaq.

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We are not subject to Nasdaq Listing Rule 5605(b)(2) because English law does not require that independent directors regularly have scheduled meetings at which only independent directors are present.

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These rules and regulations could also make it more difficult for us to attract and retain qualified members of our board of directors.

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Provisions in the U.K.

City Code on Takeovers and Mergers that may have anti-takeover effects do not currently apply to us.

City Code on Takeovers and Mergers (the “Takeover Code”), applies to an offer for, among other things, a public company whose registered office is in the UK if the company is considered by the Panel on Takeovers and Mergers (the “Takeover Panel”), to have its place of central management and control in the UK (or the Channel Islands or the Isle of Man).

This is known as the “residency test.” The test for central management and control under the Takeover Code is different from that used by the UK tax authorities.

Under the Takeover Code, the Takeover Panel will determine whether we have our place of central management and control in the UK by looking at various factors, primarily where the directors are resident.

City Code on Takeovers and Mergers (the “Takeover Code”), applies to an offer for, among other things, a public company whose registered office is in the U.K.

if the company is considered by the Panel on Takeovers and Mergers (the “Takeover Panel”), to have its place of central management and control in the U.K.

(or the Channel Islands or the Isle of Man).

This is known as the “residency test.” The test for central management and control under the Takeover Code is different from that used by the U.K.

tax authorities.

Under the Takeover Code, the Takeover Panel will determine whether we have our place of central management and control in the U.K.

by looking at various factors, primarily where the directors are resident.

In June 2019, the Takeover Panel Executive confirmed that, based on our current circumstances, we are not subject to the Takeover Code.

As a result, our shareholders are not entitled to the benefit of certain takeover offer protections provided under the Takeover Code.

We believe that this position is unlikely to change at any time in the near future but, in accordance with good practice, we will review the situation on a regular basis and consult with the Takeover Panel if there is any change in our circumstances which may have a bearing on whether the Takeover Panel would determine our place of central management and control to be in the UK.

You may face difficulties in protecting your interests, and your ability to protect your rights through the U.S.

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federal securities laws.

The United States and the UK do not currently have a treaty providing for recognition and enforcement of judgments (other than arbitration awards) in civil and commercial matters.

The United States and the U.K.

do not currently have a treaty providing for recognition and enforcement of judgments (other than arbitration awards) in civil and commercial matters.

Consequently, a final judgment for payment given by a court in the United States, whether or not predicated solely upon U.S.

securities laws, would not automatically be recognized or enforceable in the UK.

In addition, uncertainty exists as to whether English courts would entertain original actions brought in the UK against us or our directors or senior management predicated upon the securities laws of the United States or any state in the United States.

securities laws, would not automatically be recognized or enforceable in the U.K..

In addition, uncertainty exists as to whether English courts would entertain original actions brought in the U.K.

against us or our directors or senior management predicated upon the securities laws of the United States or any state in the United States.

Any final and conclusive monetary judgment for a definite sum obtained against us in U.S.

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We obtained authority from our shareholders at our Annual General Meeting held on June 28, 2024 to allot additional shares (or to grant rights to subscribe for or to convert any security into our shares) for a period of five years from June 28, 2024, up to a maximum nominal amount of $8,400, which authorization will need to be renewed upon expiration (i.e., at least every five years) but may be sought more frequently for additional five-year terms (or any shorter period).

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English law also generally provides shareholders with preemptive rights when new shares are issued for cash.

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What changed 10-K

Item 1A. Risk Factors