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What changed in Autolus Therapeutics plc's 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Autolus Therapeutics plc's 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+809 added−751 removedSource: 10-K (2026-03-27) vs 10-K (2024-12-31)

Top changes in Autolus Therapeutics plc's 2025 10-K

809 paragraphs added · 751 removed · 522 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

213 edited+111 added−113 removed331 unchanged
Biggest changeEmployees and Human Capital Resources As of December 31, 2024, we had 647 full-time employees, 65 of whom hold Ph.D. or M.D. degrees, as shown in the table below: At December 31, 2024 2023 Function: Sales and general administration 173 80 Research and development including manufacturing 474 383 Total 647 463 Geography: U.K. 495 391 Switzerland and Germany 18 13 United States 134 59 Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.
Biggest changeCopies of our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and amendments, if any, to those reports filed pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934, as amended, are available free of charge through our website and on the website of the SEC at www.sec.gov. 47 Table of contents Employees and Human Capital Resources As of December 31, 2025, we had 752 full-time employee s, 113 of whom hold Ph.D. or M.D. degrees, as sh own in the table below: At December 31, 2025 2024 Function: Sales and general administration 209 173 Research and development including manufacturing 543 474 Total 752 647 Geography: U.K. 583 495 Switzerland and Germany 20 18 United States 149 134 Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and additional employees.
Competition There are two direct in class competitors to AUCATZYL approved for the treatment of adult patients with r/r B-ALL: the autologous CAR therapies Tecartus and Kymriah. Tecartus is approved for use in adult B-ALL and Kymriah is approved for use in adolescents and young adults, (i.e., patients up to the age of 25).
Competition for AUCATZYL There are two direct in class competitors to AUCATZYL approved for the treatment of adult patients with r/r B-ALL: the autologous CAR therapies Tecartus and Kymriah. Tecartus is approved for use in adult B-ALL and Kymriah is approved for use in adolescents and young adults ( i.e. , patients up to the age of 25).
The current standard of care for both pediatric and adult B-cell ALL patients is a standard regimen of combination chemotherapy. Pediatric patients typically respond well to the complex first-line chemotherapy treatment. According to the American Cancer Society, the five-year survival rate for children with B-cell ALL is more than 85% overall.
The current standard of care for both pediatric and adult B-ALL patients is a standard regimen of combination chemotherapy. Pediatric patients typically respond well to the complex first-line chemotherapy treatment. According to the American Cancer Society, the five-year survival rate for children with B-cell ALL is more than 85% overall.
The product option for AUTO1/22 was not exercised and has expired as of February 8, 2025 ; • an option to obtain an exclusive worldwide license to exploit products that express certain additional binders in vivo or, with respect to certain binders, in an antibody drug conjugate (“Binder Option”); • an option to obtain a co-exclusive worldwide license to exploit products that express in vivo our modules for activity enhancement, with a non-exclusive right, in certain agreed instances, to exploit products that include our modules for activity enhancement but do not express in vivo such modules (the “Activity Enhancement Option”); and • an option to obtain a non-exclusive worldwide license to exploit products that contain our safety switches (the “Safety Switch Option” and, together with the Binder Option and the Activity Enhancement Option, the “Technology Options”).
The product option for AUTO1/22 was not exercised and has expired as of 8 February 2025 ; • an option to obtain an exclusive worldwide license to exploit products that express certain additional binders in vivo or, with respect to certain binders, in an antibody drug conjugate (“Binder Option”); • an option to obtain a co-exclusive worldwide license to exploit products that express in vivo our modules for activity enhancement, with a non-exclusive right, in certain agreed instances, to exploit products that include our modules for activity enhancement but do not express in vivo such modules (the “Activity Enhancement Option”); and • an option to obtain a non-exclusive worldwide license to exploit products that contain our safety switches (the “Safety Switch Option” and, together with the Binder Option and the Activity Enhancement Option, the “Technology Options”).
Government authorities in the United States (at the federal, state and local level) and in other countries and jurisdictions, including the EU, extensively regulate, among other things, the research, development, preclinical and clinical testing, manufacturing, quality control, labeling, packaging, storage, record-keeping, promotion, advertising, sale, distribution, post-approval monitoring and reporting, marketing and export and import of biopharmaceutical products such as those we are developing.
Government authorities in the United States (at the federal, state and local level) and in other countries and jurisdictions, including the United Kingdom and EU, extensively regulate, among other things, the research, development, preclinical and clinical testing, manufacturing, quality control, labeling, packaging, storage, record-keeping, promotion, advertising, sale, distribution, post-approval monitoring and reporting, marketing and export and import of biopharmaceutical products such as those we are developing.
Adult patients with relapsed or refractory FL after two or more lines of systemic therapy. *Indication based on United States Prescribing Information (USPI) Four of these products, Tecartus and Yescarta from Kite/Gilead, Kymriah from Novartis and Breyanzi from BMS are anti-CD19 CAR T cell therapies, the same class as obe-cel.
Adult patients with relapsed or refractory FL after two or more lines of systemic therapy. *Indication based on United States Prescribing Information Four of these products, Tecartus and Yescarta from Kite/Gilead, Kymriah from Novartis and Breyanzi from BMS are anti-CD19 CAR T cell therapies, the same class as obe-cel.
Further, pharmaceutical manufacturers can be held liable under the U.S. federal False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. 35 Table of contents The U.S. federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), created new federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third- party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.
Further, pharmaceutical manufacturers can be held liable under the U.S. federal False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. 37 Table of contents The U.S. federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”), created new federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third- party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.
Background of Pediatric ALL According to the American Cancer Society, B-cell ALL is most common in childhood, peaking between two and four years of age. As per the National Cancer Institute Surveillance, Epidemiology and End Results statistics database, there are approximately 3,400 new cases of pediatric ALL diagnosed in the United States each year.
Background of Pediatric ALL According to the American Cancer Society, B-ALL is most common in childhood, peaking between two and four years of age. As per the National Cancer Institute Surveillance, Epidemiology and End Results statistics database, there are approximately 3,400 new cases of pediatric B-ALL diagnosed in the United States each year.
Specifically, the Regulation, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the “EU portal” the Clinical Trials Information System (“CTIS”); a single set of documents to be prepared and submitted for the application; as well as simplified reporting procedures for clinical trial sponsors.
Specifically, the Regulation, which is directly applicable in all EU Member States, introduces a streamlined application procedure through a single-entry point, the “EU portal” the Clinical Trials Information System; a single set of documents to be prepared and submitted for the application; as well as simplified reporting procedures for clinical trial sponsors.
Post-Approval Requirements Any products for which we receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as “off-label use”), limitations on industry-sponsored scientific and educational activities, and requirements that important safety information and material facts related to the product be disclosed.
Post-Approval Requirements Any products for which we receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, periodic reports, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as “off-label use”), limitations on industry-sponsored scientific and educational activities, and requirements that important safety information and material facts related to the product be disclosed.
In addition, under the Pediatric Research Equity Act (“PREA”), a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
In addition, under the Pediatric Research Equity Act, a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Medicines used in clinical trials, including ATMPs, must be manufactured in accordance with the guidelines on cGMP and in a GMP licensed facility, which can be subject to GMP inspections. Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Conference on Harmonization (“ICH”), guidelines on GCP.
Medicines used in clinical trials, including ATMPs, must be manufactured in accordance with the guidelines on cGMP and in a GMP licensed facility, which can be subject to GMP inspections. Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Conference on Harmonization, guidelines on GCP.
However, guidance from the EMA states that they will be considered in the future in light of the scientific knowledge and regulatory experience gained at the time. 41 Table of contents Pediatric Development In the EU, Regulation (EC) No 1901/2006 provides that all MAAs for new medicinal products have to include the results of trials conducted in the pediatric population, in compliance with a pediatric investigation plan (“PIP”), agreed with the EMA’s Pediatric Committee (“PDCO”).
However, guidance from the EMA states that they will be considered in the future in light of the scientific knowledge and regulatory experience gained at the time. 43 Table of contents Pediatric Development In the EU, Regulation (EC) No 1901/2006 provides that all MAAs for new medicinal products have to include the results of trials conducted in the pediatric population, in compliance with a pediatric investigation plan (“PIP”), agreed with the EMA’s Pediatric Committee (“PDCO”).
While the products we have in development do not make use of embryonic stem cells, it is possible that the national laws in certain EU Member States may prohibit or restrict us from commercializing our products, even if they have been granted an EU marketing authorization. 40 Table of contents Advanced Therapy Medicinal Products Advanced Therapy Medicinal Products, or ATMPs, include gene therapy products as well as somatic cell therapy products and tissue engineered products.
While the products we have in development do not make use of embryonic stem cells, it is possible that the national laws in certain EU Member States may prohibit or restrict us from commercializing our products, even if they have been granted an EU marketing authorization. 42 Table of contents Advanced Therapy Medicinal Products Advanced Therapy Medicinal Products, or ATMPs, include gene therapy products as well as somatic cell therapy products and tissue engineered products.
As of November 13, 2023 (data cut-off), 11 patients have been infused with either BCMA CAR at 50 million (n=3) or 150 million (n=3) cells, or AUTO8 at 50 million (n=3) or 150 million (n=2). At a median follow-up of 6 months we observed 100% response rate (ORR), with 3 PR, 1 VGPR, 7 CR/sCR (all evaluable MRD negative).
As of November 13, 2023 (data cut-off), 11 patients have been infused with either BCMA CAR at 50 million (n=3) or 150 million (n=3) cells, or AUTO8 at 50 million (n=3) or 150 million (n=2). At a median follow-up of 6 months we observed 100% ORR, with 3 PR, 1 VGPR, 7 CR/sCR (all evaluable MRD negative).
Checkpoint Shielding (dSHP2) Immune checkpoint receptors act through a common signaling pathway inside the T cell that prevents normal T cell activation. We have developed a modified version of an adaptor protein, SHP2, that in preclinical studies has been shown to efficiently counteract the inhibition of T cells resulting from the PD-L1/PD-1 interaction.
Checkpoint Shielding (dSHP2) Immune checkpoint receptors act through a common signalling pathway inside the T cell that prevents normal T cell activation. We have developed a modified version of an adaptor protein, SHP2, that in preclinical studies has been shown to efficiently counteract the inhibition of T cells resulting from the PD-L1/PD-1 interaction.
Upon CD19 directed CAR T cell therapies, it also leads to B-cell aplasia which can be used as a pharmacodynamic marker. CD19 CAR T cell therapies have proven effective in treating B-cell leukemias, B-cell lymphoma and early evidence suggest they are effective in treating b-cell mediated autoimmune diseases. Efficacy is dependent on engraftment and expansion of the CAR T cells.
Upon CD19 directed CAR T cell therapies, it also leads to B-cell aplasia which can be used as a pharmacodynamic marker. CD19 CAR T cell therapies have proven effective in treating B-cell leukaemias, B-cell lymphoma and early evidence suggest they are effective in treating b-cell mediated autoimmune diseases. Efficacy is dependent on engraftment and expansion of the CAR T cells.
Severe ICANS post-obe-cel were seen as largely limited to patients with high BM burden pre-lymphodepletion. Intensive care unit (ICU) admissions occurred in 20 (15.7%) patients for a median of 5.5 days (range,1−37) of which 7/20 were admitted due to immunotoxicity management (5 ICANS, 2 CRS).
Severe ICANS post-obe-cel were seen as largely limited to patients with high BM burden pre-lymphodepletion. Intensive care unit admissions occurred in 20 (15.7%) patients for a median of 5.5 days (range: 1−37) of which 7 of the 20 patients were admitted due to immunotoxicity management (5 ICANS, 2 CRS).
For example, we are pursuing patent protection for core constructs used in our product candidates, various methods of treatment for particular therapeutic indications using our approach, specific product candidates, innovative manufacturing processes, and constructs that may be used in future product candidates to improve the ability of our programmed T cells to better recognize and kill cancer cells.
For example, we are pursuing patent protection for core constructs used in our product candidates, various methods of treatment for particular therapeutic indications using our approach, specific product candidates, innovative manufacturing processes, and constructs that may be used in future product candidates to improve the ability of our programmed T cells to better recognize and kill cancer and other target cells.
The conditional MA is subject to conditions to be fulfilled for generating the missing data or ensuring increased safety measures. It is valid for one year and must be renewed annually until all related conditions have been fulfilled. Once any pending studies are provided, the conditional MA can be converted into a traditional MA.
The conditional MA is subject to conditions to be fulfilled for generating the missing data or ensuring increased safety measures. It is valid for one year and must be renewed annually until all related conditions have been fulfilled. Once any pending studies are provided, the conditional MA can be converted into a full MA.
We believe obe-cel has a differentiated safety profile and shows potential for longer term outcomes when compared to these current approved therapies. In addition, it is possible that companies could take other autologous CAR T cell products forward in adult ALL or allogeneic “off-the-shelf” CAR T cell therapies could be developed which would be considered direct competitors.
We believe AUCATZYL has a differentiated safety profile and shows potential for longer term outcomes when compared to these current approved therapies. In addition, it is possible that companies could take other autologous CAR T cell products forward in adult ALL or allogeneic “off-the-shelf” CAR T cell therapies could be developed which would be considered direct competitors.
In addition, it is designed to simultaneously disarm multiple inhibitory receptors on the cancer cell. We use the dSHP shielding module in our AUTO6NG program. Enhanced Activity One of the challenges of targeting some solid tumors is the lack of such easily accessible stimulation for programmed T cells, leading to poor persistence and a weak anti-tumor activity.
In addition, it is designed to simultaneously disarm multiple inhibitory receptors on the cancer cell. We use the dSHP shielding module in our AUTO6NG program. Enhanced Activity One of the challenges of targeting some solid tumors is the lack of such easily accessible stimulation for programmed T cells, leading to poor persistence and a weak antitumor activity.
Furthermore, additional evidence of CD19 CAR T cell treatment in other autoimmune diseases has been shown by others, including efficacy in patients with idiopathic inflammatory myositis, systemic sclerosis, myasthenia gravis and multiple sclerosis. Depending on the outcome of the dose confirmation study in SLE, we would plan to investigate obe-cel in additional autoimmune disease indications.
Furthermore, additional evidence of CD19 CAR T cell treatment in other autoimmune diseases has been shown by others, including efficacy in patients with idiopathic inflammatory myositis, systemic sclerosis, myasthenia gravis and multiple sclerosis. Depending on the outcome of the dose confirmation study in SLE, we intend to investigate obe-cel in additional autoimmune disease indications.
The process required by the FDA before a biological product may be approved for marketing in the United States generally involves the following: • completion of preclinical laboratory tests and animal studies according to Good Laboratory Practices (“GLPs”), and applicable requirements for the humane use of laboratory animals or other applicable regulations; • submission to the FDA of an Investigational New Drug Application (“IND”), which must become effective before human clinical trials may begin; • performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as Good Clinical Practices (“GCPs”), and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed biological product for its intended use; • preparation and submission to the FDA of a BLA, for marketing approval that includes substantive evidence of quality, efficacy, and safety from results of nonclinical testing and clinical trials; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities where the biological product is produced to assess compliance with cGMP to assure that the facilities, methods and controls used in product manufacture are adequate to preserve the biological product’s identity, strength, quality and purity and, if applicable, the FDA’s current Good Tissue Practices (“GTPs”) for the use of human cellular and tissue products; • potential FDA inspection of the nonclinical study and clinical trial sites that generated the data in support of the BLA; • payment of user fees for FDA review of the BLA; and • FDA acceptance, review and approval, of the BLA, which might include review by an advisory committee, a panel typically consisting of independent clinicians and other experts who provide recommendations as to whether the application should be approved and under what conditions. 30 Table of contents Before testing any biological product candidate, including our product candidates, in humans, the product candidate must undergo rigorous preclinical testing.
The process required by the FDA before a biological product may be approved for marketing in the United States generally involves the following: • completion of preclinical laboratory tests and animal studies according to Good Laboratory Practices (“GLPs”), and applicable requirements for the humane use of laboratory animals or other applicable regulations; • submission to the FDA of an Investigational New Drug Application (“IND”), which must become effective before human clinical trials may begin; • performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as Good Clinical Practices (“GCPs”), and any additional requirements for the protection of human research subjects and their health information, to establish the safety and efficacy of the proposed biological product for its intended use; • preparation and submission to the FDA of a BLA, for marketing approval that includes substantive evidence of quality, efficacy, and safety from results of nonclinical testing and clinical trials; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities where the biological product is produced to assess compliance with cGMP to assure that the facilities, methods and controls used in product manufacture are adequate to preserve the biological product’s identity, strength, quality and purity and, if applicable, the FDA’s current Good Tissue Practices (“GTPs”) for the use of human cellular and tissue products; • potential FDA inspection of the nonclinical study and clinical trial sites that generated the data in support of the BLA; • payment of user fees for FDA review of the BLA; and • FDA acceptance, review and approval, of the BLA, which might include review by an advisory committee, a panel typically consisting of independent clinicians and other experts who provide recommendations as to whether the application should be approved and under what conditions.
Safety switches are designed to selectively eliminate the programmed T cells following administration of a pharmacological agent, whilst tuneable or controllable CAR T cells allow the activity of T cell therapy to be dialed down following administration of a pharmacological agent.
Safety switches are designed to selectively eliminate the programmed T cells following administration of a pharmacological agent, whilst tuneable or controllable CAR T cells allow the activity of T cell therapy to be dialled down following administration of a pharmacological agent.
In the EU, the advertising and promotion of medicinal products are subject to both EU and EU Member States’ laws governing promotion of medicinal products, interactions with physicians and other healthcare professionals, misleading and comparative advertising and unfair commercial practices.
Other EU Compliance Requirements In the EU, the advertising and promotion of medicinal products are subject to both EU and EU Member States’ laws governing promotion of medicinal products, interactions with physicians and other healthcare professionals, misleading and comparative advertising and unfair commercial practices.
In exchange for the grant of rights to future revenues from the sales of obe-cel, BioNTech has made an upfront payment to us of $40 million (representing the remainder of the $50 million total upfront payment).
In exchange for the grant of rights to future revenues from the sales of obe-cel, BioNTech has made an upfront payment to us of $40 million, ( £31.8 million), representing the remainder of the $50 million total upfront payment).
The term ‘‘remuneration’’ has been broadly interpreted to include anything of value. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand.
The term “remuneration” has been broadly interpreted to include anything of value. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand.
Data Privacy and Security Laws In the ordinary course of our business, we and the third parties with whom we work process personal or sensitive data, including data we collect in connection with our clinical trial activities.
Data Privacy and Security Laws In the ordinary course of our business, we and the third parties with whom we work process personal or sensitive data, including data we collect in connection with our commercial and clinical activities.
For those patients experiencing a relapse, the common causes for relapse are insufficient survival of the programmed T cells, loss of the CD19 target on the cancer cells and upregulation of checkpoint inhibitor PD-L1 on the cancer cells. In view of the limitations of current therapies, there remains a critical unmet medical need for improved T cell therapies.
For those patients experiencing a relapse, the common causes for relapse are insufficient survival of the programmed T cells, loss of the CD19 target on the cancer cells and upregulation of checkpoint inhibitor PD-L1 on the cancer cells. 10 Table of contents In view of the limitations of current therapies, there remains a critical unmet medical need for improved T cell therapies.
These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. 31 Table of contents During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators.
These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up. During all phases of clinical development, regulatory agencies require extensive monitoring and auditing of all clinical activities, clinical data, and clinical trial investigators.
The manufacturing agreements governing the external supply arrangements also provide for access to services including quality management systems, qualified persons for product release, office space, frozen storage and warehousing services. 16 Table of contents In March 2018, we entered into a strategic, long-term supply agreement with Miltenyi Biotec GmbH (“Miltenyi”), for the supply of Miltenyi’s CliniMACS Prodigy instruments, reagents and disposables for the manufacture of our programmed T cell therapies, including for commercial production of AUCATZYL as well as for preclinical and clinical use, as well as support services.
The manufacturing agreements governing the external supply arrangements also provide for access to services including quality management systems, qualified persons for product release, office space, frozen storage and warehousing services. 16 Table of contents In March 2018, we entered into a strategic, long-term supply agreement with Miltenyi Biotec GmbH (“Miltenyi”), for the supply of Miltenyi’s CliniMACS Prodigy instruments, reagents and disposables for the manufacture of our programmed T cell therapies, including for pre-clinical, clinical and commercial production of AUCATZYL, as well as the provision of related support services.
One such inhibitory factor is Fas ligand ( “ FasL ” ), which binds to the Fas receptor (CD95) on the surface of an activated T cell and triggers the CAR T cell to die by apoptosis. Our Fas chimeras consist of the extracellular domain of Fas fused to the intracellular domain from different TNF receptor superfamily members.
One such inhibitory factor is Fas ligand (“FasL”), which binds to the Fas receptor (CD95) on the surface of an activated T cell and triggers the CAR T cell to die by apoptosis. Our Fas chimeras consist of the extracellular domain of Fas fused to the intracellular domain from different TNF receptor superfamily members.
To the extent that our consultants, contractors or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. 25 Table of contents We also protect our brand via the use of trademarks.
To the extent that our consultants, contractors or collaborators use intellectual property owned by others in their work for us, disputes may arise as to the rights in related or resulting know-how and inventions. We also protect our brand via the use of trademarks.
Co-administration with cytokines can boost T cell activity and persistence. Certain cytokines can potentiate the anti-tumor of the T cell therapy by recruiting and activating other immune cells to kill the tumor.
Co-administration with cytokines can boost T cell activity and persistence. Certain cytokines can potentiate the antitumor of the T cell therapy by recruiting and activating other immune cells to kill the tumor.
A company may voluntarily remove a product from the register of orphan products. Post-Approval Controls Where a MA is granted in relation to a medicinal product in the EU, the holder of the MA is required to comply with a range of regulatory requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products.
A company may voluntarily remove a product from the register of orphan products. 44 Table of contents Post-Approval Controls Where a MA is granted in relation to a medicinal product in the EU, the holder of the MA is required to comply with a range of regulatory requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products.
Travel Act prohibit the provision of improper payments and benefits to government and private-sector recipients within the United States. 37 Table of contents Our operations are also subject to non-U.S. anti-corruption laws such as the UK Bribery Act 2010 (the “UK Bribery Act”).
Travel Act prohibit the provision of improper payments and benefits to government and private-sector recipients within the United States. Our operations are also subject to non-U.S. anti-corruption laws such as the UK Bribery Act 2010 (the “UK Bribery Act”).
However, only Tecartus is approved for use in adult ALL with Kymriah also being an option for adolescents and young adults, (i.e., patients up to the age of 25 years old). We believe there will be a market for obe-cel in this indication due to its differentiated safety profile when compared to current approved therapies.
However, only Tecartus is approved for use in adult ALL with Kymriah also being an option for adolescents and young adults, (i.e., patients up to the age of 25 years old). There is a market for obe-cel in this indication due to its differentiated safety profile when compared to current approved therapies.
These modules are delivered, or transduced, into the T cells via two viral vectors. Both single- and dual-transduced CAR T cells were evaluated in vitro for anti-tumor activity, cytokine secretion, T cell proliferation, survival, and resistance to immunosuppressive pathways.
These modules are delivered, or transduced, into the T cells via two viral vectors. Both single- and dual-transduced CAR T cells were evaluated in vitro for antitumor activity, cytokine secretion, T cell proliferation, survival, and resistance to immunosuppressive pathways.
All apheresis starting material was successfully processed despite the multitude of constraints posed by the COVID-19 pandemic. In total, 96% of manufactured obe-cel batches reached their target dose of 410 x 106 CAR T cells.
All apheresis starting material was successfully processed despite the multitude of constraints posed by the COVID-19 pandemic. In total, 96% of manufactured obe-cel batches reached their target dose of 410 x 10 6 CAR T cells.
In 2024, $0.1 million was payable to UCLB by us relating to the income allocable to the value of the sublicensed intellectual property rights. UCLB has retained the right to use the licensed T cell programming modules for academic research purposes at UCL and with other academic institutions, subject to certain restrictions.
In 2025, less than $0.1 million was payable to UCLB by us relating to the income allocable to the value of the sublicensed intellectual property rights. UCLB has retained the right to use the licensed T cell programming modules for academic research purposes at UCL and with other academic institutions, subject to certain restrictions.
Such obligations may include, without limitation, the Federal Trade Commission Act, HIPAA, as amended by the HITECH, the EU’s General Data Protection Regulation 2016/679 (“EU GDPR”), the EU GDPR as it forms part of U.K. law by virtue of section 3 of the EU (Withdrawal) Act 2018 (“UK GDPR”), and the ePrivacy Directive and local implementations thereof, including the U.K.’s Privacy and Electronic Communications Regulations 2003.
Such obligations may include, without limitation, the Federal Trade Commission Act, HIPAA, as amended by the HITECH, the European Union’s General Data Protection Regulation 2016/679 (“EU GDPR”), the EU GDPR as it forms part of U.K. law by virtue of section 3 of the EU (Withdrawal) Act 2018 (“UK GDPR”) (collectively, “GDPR”), and the ePrivacy Directive and local implementations thereof, including the U.K.’s Privacy and Electronic Communications Regulations 2003.
Approximately 10% of patients with lupus nephritis (“LN”), a form of the disease associated with kidney organ damage, develop end-stage renal disease in 5 years . Side effects of the current treatment strategies include infections in the short term and risk for malignancy and cardiovascular disease in the long term, contributing to the reduced life expectancy of patients with SLE.
Approximately 10% of patients with LN, a form of the disease associated with kidney organ damage, develop end-stage renal disease in 5 years. Side effects of the current treatment strategies include infections in the short term and risk for malignancy and cardiovascular disease in the long term, contributing to the reduced life expectancy of patients with SLE.
As of December 31, 2024, our trademark portfolio consists of 5 trademark families covering our core brand and product. These families include protection in commercially relevant jurisdictions, including the U.S. and Europe. We have established internal guidelines for the use of our brands and monitor for the registration of similar marks by third parties.
As of December 31, 2025, our trademark portfolio consists of 4 trademark families covering our core brand and product. These families include protection in commercially relevant jurisdictions, including the U.S. and Europe. We have established internal guidelines for the use of our brands and monitor for the registration of similar marks by third parties.
Once administered, tetracycline temporarily dislocates the CAR signaling domain from the cancer antigen binding domain leading to deactivation of the T cell therapy. Activity is then restored on clearance of the pharmacological agent from the patient. Tumor Microenvironment Shielding Tumor cells and other cells in the tumor microenvironment can debilitate anti-tumor immune responses.
Once administered, tetracycline temporarily dislocates the CAR signalling domain from the cancer antigen binding domain leading to deactivation of the T cell therapy. Activity is then restored on clearance of the pharmacological agent from the patient. Tumor Microenvironment Shielding Tumor cells and other cells in the tumor microenvironment can debilitate antitumor immune responses.
The process for obtaining regulatory marketing approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. U.S.
The process for obtaining regulatory marketing approvals and the subsequent compliance with applicable federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources. 31 Table of contents U.S.
We believe our leadership in T cell programming technologies will provide us with a competitive advantage as we look to develop future generations of T cell therapies targeting both hematological cancers, solid tumors and autoimmune diseases, including potential products that could have a sufficient tolerability profile to enable use in outpatient settings. 7 Table of contents Our Pipeline Our current clinical-stage pipeline comprises five programs being developed in seven hematological and solid tumor indications and one autoimmune indication.
We believe our leadership in T cell programming technologies will provide us with a competitive advantage as we look to develop future generations of T cell therapies targeting both hematological cancers, solid tumors and autoimmune diseases, including potential products that could have a sufficient tolerability profile to enable use in outpatient settings. 7 Table of contents Our Pipeline Our current clinical-stage pipeline comprises four programs being developed in eight hematological and solid tumor indications and two autoimmune indications.
Assistance is given by the EMA’s Committee for Medicinal Products for Human Use, or CHMP, on the recommendation of the Scientific Advice Working Party. A fee is incurred with each scientific advice procedure.
Assistance is given by the EMA’s Committee for Medicinal Products for Human Use (“CHMP”) on the recommendation of the Scientific Advice Working Party. A fee is incurred with each scientific advice procedure.
We plan to expand our global commercialization capabilities over time such that we are able to commercialize any product candidate in a broader number of countries over time, but with a focus on achieving an early presence in the U.S., U.K. and parts of Europe, i.e. countries where we expect to obtain a regulatory approval.
We plan to expand our global commercialization capabilities over time such that we are able to commercialize any product candidate in a broader number of countries over time, but with a focus on achieving an early presence in the US, U.K. and parts of Europe, i.e. countries where we have obtained a regulatory approval.
GD2 was evaluated as a therapeutic CAR T target antigen in SCLC. We observed that AUTO6 alone has demonstrated efficacy in an in vitro SCLC model; however, successful tumor targeting alone was not sufficient to drive meaningful in vivo efficacy in the same SCLC model.
GD2 was evaluated as a therapeutic CAR T target antigen in small cell lung cancer (“SCLC”). We observed that AUTO6 alone has demonstrated efficacy in an in vitro SCLC model; however, successful tumor targeting alone was not sufficient to drive meaningful in vivo efficacy in the same SCLC model.
We presented new preclinical data demonstrating the ability to target GD2 in SCLC cell line models in vitro, and the requirement for enhancing modules, designed to overcome TME suppressive mechanisms, to drive superior in vivo efficacy in a SCLC mouse model. The data suggests that AUTO6NG can overcome the immune suppressive mechanisms in the TME.
We presented new preclinical data demonstrating the ability to target GD2 in SCLC cell line models in vitro, and the requirement for enhancing modules, designed to overcome TME suppressive mechanisms, to drive superior in vivo efficacy in a SCLC mouse model.
This study is currently enrolling patients Commercialization and Manufacturing Plans for our Clinical-Stage Programs We are developing our clinical-stage programs for the treatment of patients with late-stage or rare hematological cancers and solid tumors, most of whom are treated in specialized treatment centers or hospitals.
Commercialization and Manufacturing Plans for our Clinical-Stage Programs We are developing our clinical-stage programs for the treatment of patients with late-stage or rare hematological cancers and solid tumors, most of whom are treated in specialized treatment centers or hospitals.
In addition to the standard sales & marketing elements and medical affairs activities required to successfully commercialize an oncology/hematology product, there are several additional requirements needed for commercializing CAR-T cell therapies. This required several bespoke elements, including the processes for distribution, patient scheduling, center engagement and service hub to be established.
In addition to the standard sales & marketing elements and medical affairs activities required to successfully commercialize an oncology/hematology product, there are several additional requirements needed for effectively commercializing CAR-T cell therapies, including bespoke processes for distribution, patient scheduling, center engagement and a dedicated treatment center service hub.
If a Complete Response Letter is issued, the applicant may either resubmit the BLA, addressing all of the deficiencies identified in the letter, or withdraw the application. If a product receives regulatory approval, the approval is limited to the conditions of use (e.g., patient population, indication) described in the application.
If a Complete Response Letter is issued, the applicant may either submit information to the BLA, addressing all of the deficiencies identified in the letter, or withdraw the application. 34 Table of contents If a product receives regulatory approval, the approval is limited to the conditions of use (e.g., patient population, indication) described in the application.
Additionally, intravenous delivery of AUTO6NG in mice with established tumor burden exhibited potent anti-tumor activity and extended survival, whereas AUTO6 showed no activity in that model. 23 Table of contents We presented new preclinical data for AUTO6NG in June 2020 at the American Association for Cancer Research (“AACR ” ) Virtual Annual Meeting 2020.
Additionally, intravenous delivery of AUTO6NG in mice with established tumor burden exhibited potent antitumor activity and extended survival, whereas AUTO6 showed no activity in that model. We presented new preclinical data for AUTO6NG in June 2020 at the American Association for Cancer Research Virtual Annual Meeting 2020.
We may pursue strategic collaborations with third parties in order to maximize the commercial potential of our product candidates. Under the terms of the License and Option Agreement with BioNTech, BioNTech has certain options to co-promote or co-commercialize AUTO1/22 and AUTO6NG.
We may pursue strategic collaborations with third parties in order to maximize the commercial potential of our product candidates. Under the terms of the License and Option Agreement with BioNTech, BioNTech currently has an option to co-promote or co-commercialize AUTO6NG.
A viral vector is used to introduce combinations of these modules into the DNA of the T cells, as depicted in the graphic below. The diagram below shows how our programming modules relate to our product candidates.
A viral vector is then used to introduce combinations of these modules into the DNA of the T cells. The diagram below shows how our programming modules relate to our product candidates.
However, the majority of these remissions are not long-lasting in adult patients. Despite this initial CR, and in contrast to pediatric ALL, the prognosis of adult ALL is still poor and has not changed significantly during the last two to three decades, with long-term remission rates limited to 30-40%.
Combination chemotherapy enables 90% of adult patients to experience complete remission (“CR”). However, the majority of these remissions are not long-lasting in adult patients. Despite this initial CR, and in contrast to pediatric ALL, the prognosis of adult ALL is still poor and has not changed significantly during the last two decades, with long-term remission rates limited to 30-40%.
Obe-cel for the Treatment of Pediatric ALL, B-NHL and other B-cell malignancies In addition to AUCATZYL/obe-cel for the treatment of adult r/r B-ALL, we are advancing obe-cel in other oncology indications including pediatric B-ALL and B-NHL, for which we have initiated Phase 1 studies.
Obe-cel for the Treatment of Pediatric ALL, B-NHL and other B-cell malignancies In addition to AUCATZYL/obe-cel for the treatment of adult r/r B-ALL, we are advancing obe-cel in other oncology indications including pediatric B-ALL and B-NHL, for which we have initiated the Phase 1b/2 CATULUS trial.
Median duration of CAR T persistence by droplet digital PCR (ddPCR) in peripheral blood was 17.8 months. Obe-cel was associated with minimal immunotoxicity. CRS and Immune effector cell-associated neurotoxicity syndrome (“ICANS”) rates (Grade ≥3) were 2.4% and 7.1%, respectively. Overall, 87 (68.5%) patients developed CRS, and 29 (22.8) developed ICANS.
Median duration of CAR T persistence by droplet digital PCR (ddPCR) in peripheral blood was 17.8 months. 14 Table of contents Obe-cel was associated with minimal immunotoxicity. CRS and ICANS rates (Grade ≥3) were 2.4% and 7.1%, respectively. Overall, 87 (68.5%) patients developed CRS, and 29 (22.8) developed ICANS.
SPC is the document that provides information to physicians concerning the safe and effective use of the product. Promotional activity that does not comply with the U.K.
SPC is the document that provides information to physicians concerning the safe and effective use of the product. Promotional activity that does not comply with the U.K. SPC is considered off-label and is prohibited in the U.K.
We have established a manufacturing process that is scalable and serves as a manufacturing platform designed to support rapid development of our programmed T cell therapy product candidates through clinical trial phases and regulatory approval processes.
Commercial success in T cell therapies requires a manufacturing process that is reliable, scalable and economical. We have established a manufacturing process that is scalable and serves as a manufacturing platform designed to support rapid development of our programmed T cell therapy product candidates through clinical trial phases and regulatory approval processes.
Patients are unlikely to use a product, and physicians may be less likely to prescribe a product, unless coverage is provided and reimbursement is adequate to cover all or a significant portion of the cost of the product. Therefore, coverage and adequate reimbursement is critical to new drug product acceptance.
Patients are unlikely to use a product, and physicians may be less likely to prescribe a product, unless coverage is provided and reimbursement is adequate to cover all or a significant portion of the cost of the product. Therefore, coverage and adequate reimbursement is critical to new drug product acceptance. Different pricing and reimbursement schemes exist in other countries.
For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative or for which a centralized process is in the interest of patients, authorization through the centralized procedure is optional on related approval.
For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative or for which a centralized process is in the interest of patients, authorization through the centralized procedure is optional on related approval. Under the centralized procedure, the EMA’s CHMP, conducts the initial assessment of a product.
Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
Coverage policies and third-party reimbursement rates may change at any time. Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
The median OS in those patients, though significantly improved compared to chemotherapy, was still only 7.7 months. Similarly, in a Phase 3 clinical trial of inotuzumab ozogamicin, a higher percentage of patients achieved MRD-negative CR when treated with inotuzumab compared to standard-of-care chemotherapy, but the median duration of remission was 4.6 months and median OS was 7.7 months.
Similarly, in a Phase 3 clinical trial of inotuzumab ozogamicin, a higher percentage of patients achieved MRD-negative CR when treated with inotuzumab compared to standard-of-care chemotherapy, but the median duration of remission was 4.6 months and median OS was equally short with 7.7 months.
The SmPC is the document that provides information to physicians and other healthcare professionals concerning the safe and effective use of the product. Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU. Pricing and Reimbursement In the EU, pricing and reimbursement schemes vary widely from country to country.
The SmPC is the document that provides information to physicians and other healthcare professionals concerning the safe and effective use of the product. Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU.
Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling, or otherwise limit the scope of any approval.
Further, the FDA may require that certain contraindications, warnings or precautions, restrictions on prescription and distribution be included in the product labeling, or otherwise limit the scope of any approval.
Background of SLE Systemic lupus erythematosus (“SLE”) is an autoimmune disease characterized by the formation of autoantibodies and immune complex–mediated inflammation and organ damage, including the skin, joints, central nervous system, heart, lung, and kidneys. Disease severity changes over time with periods of no disease activity alternated by periods with disease flares/relapses. In some cases SLE can be life threatening.
Background of Systemic lupus erythematosus (“SLE”) and lupus n ephritis (“LN”) SLE is an autoimmune disease characterized by the formation of autoantibodies and immune complex–mediated inflammation and organ damage, including the skin, joints, central nervous system, heart, lung, and kidneys. Disease severity changes over time with periods of no disease activity alternated by periods with disease flares/relapses.
With currently available treatments the five-year survival rate is approximately 58%. Treatment choices for multiple myeloma vary with the aggressiveness of the disease and related prognostic factors. Newly diagnosed patients in good physical health with active disease generally receive high-dose chemotherapy with autologous stem cell transplantation (“ASCT”). Eligibility for ASCT is established primarily by age and comorbidities.
With currently available treatments the five-year survival rate is approximately 58%. 22 Table of contents Treatment choices for multiple myeloma vary with the aggressiveness of the disease and related prognostic factors. Newly diagnosed patients in good physical health with active disease generally receive high-dose chemotherapy with autologous stem cell transplantation (“ASCT”).
UCL presented initial data at the EHA meeting in June 2022. Expansion of obe-cel was observed in the peripheral blood by qPCR, with persistence in all treated patients at last follow-up. No Grade 3 or greater CRS was observed using intravenous (“IV”) or intra-ventricular obe-cel administration.
Expansion of obe-cel was observed in the peripheral blood by qPCR, with persistence in all treated patients at last follow-up. No Grade 3 or greater CRS was observed using intravenous (“IV”) or intra-ventricular obe-cel administration.
However, this class of product has not shown the same levels of durable activity and the products in clinical trials are therefore likely to require periodic repeat dosing as opposed to autologous products, which allow for the therapy to be given as a one-time treatment. CAR T cell therapies are also being evaluated for treatment of autoimmune diseases.
However, so far this class of product has not shown the same levels of durable activity in clinical trials and the products in clinical trials are therefore likely to require periodic repeat dosing as opposed to autologous products, which allow for the therapy to be given as a one-time treatment.
Orphan medicinal product designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval process. 42 Table of contents The period of market exclusivity may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria on the basis of which it received orphan medicinal product designation, including where it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold.
The period of market exclusivity may, however, be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria on the basis of which it received orphan medicinal product designation, including where it can be demonstrated on the basis of available evidence that the original orphan medicinal product is sufficiently profitable not to justify maintenance of market exclusivity or where the prevalence of the condition has increased above the threshold.
As mentioned above, we acquired ownership of the majority of the licensed patent rights under the license agreement (with the exception of the RQR8 patent rights) by virtue of a Deed of Assignment from UCLB which was executed in October 2020. Our payment and diligence obligations remain unaffected by the assignment of the licensed patent rights to us.
As mentioned above, we acquired ownership of the majority of the licensed patent rights under the license agreement (with the exception of the RQR8 patent rights) by virtue of a Deed of Assignment from UCLB which was executed in October 2020.
The manufacture and delivery of programmed T cell therapies to patients involves complex, integrated processes, including harvesting T cells from patients, manufacturing viral vectors with nucleic acid content encoded with our programming modules, manufacturing programmed T cells using the viral vectors ex vivo, multiplying the T cells to obtain the desired dose, and ultimately infusing the T cells back into a patient’s body. 15 Table of contents Commercial success in T cell therapies requires a manufacturing process that is reliable, scalable and economical.
The manufacture and delivery of programmed T cell therapies to patients involves complex, integrated processes, including harvesting T cells from patients, manufacturing viral vectors with nucleic acid content encoded with our programming modules, manufacturing programmed T cells using the viral vectors ex vivo, multiplying the T cells to obtain the desired dose, and ultimately infusing the T cells back into a patient’s body.
The estimated EFS rate with censoring of subsequent transplant or new treatment was 45% at 36 months; all patients in ongoing remission were MRD negative at last assessment and median duration of response was not reached.
After a median follow-up of 3 years and without subsequent transplant, 41% of patients continued in complete remission. The estimated EFS rate with censoring of subsequent transplant or new treatment was 45% at 36 months; all patients in ongoing remission were MRD negative at last assessment and median duration of response was not reached.
Our Product Candidates for the Treatment of Hematological Cancers and Autoimmune Diseases Our clinical-stage product candidates targeting hematological cancers are obe-cel, AUTO1/22, AUTO4 and AUTO8. We have an additional hematological product candidate, AUTO5, in preclinical development. Additionally, obe-cel is also being explored as a potential therapeutic approach targeting certain autoimmune diseases.
Our Product Candidates for the Treatment of Hematological Cancers and Autoimmune Diseases Our clinical-stage product candidates targeting hematological cancers are obe-cel, AUTO1/22 and AUTO8. Additionally, obe-cel is also being explored as a potential therapeutic approach targeting certain autoimmune diseases.
Breyanzi (lisocabtagene maraleucel) CD19 BMS Adult patients with large B-cell lymphoma (“LBCL”): • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; • refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age • relapsed or refractory disease after two or more lines of systemic therapy 28 Table of contents Carvykti (ciltacabtagene autoleucel) BCMA J&J / Janssen Biotech Adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy.
Breyanzi (lisocabtagene maraleucel) CD19 BMS Adult patients with large B-cell lymphoma (“LBCL”): • refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; • refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age • relapsed or refractory disease after two or more lines of systemic therapy Carvykti (ciltacabtagene autoleucel) BCMA J&J / Janssen Biotech Adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy. 29 Table of contents Kymriah CD19 Novartis Patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse Adult patients with LBCL after two or more lines of systemic therapy, including DLBCL Adult patients with relapsed or refractory FL after two or more lines of systemic therapy.
With this classification, commercial production of our products will need to occur in registered and licensed facilities in compliance with GMPs for biologics. Human immunotherapy products are a new category of therapeutics.
With this classification, commercial production of our products will need to occur in registered and licensed facilities in compliance with GMPs for biologics.
The maximum timeframe for the evaluation of a MAA under the centralized procedure is 210 days, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP. 39 Table of contents A MA has, in principle, an initial validity of five years.
The maximum timeframe for the evaluation of a MAA under the centralized procedure is 210 days, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeEnglish law provides that a board of directors may only allot shares (or rights to subscribe for or convertible into shares) with the prior authorization of shareholders, such authorization stating the aggregate nominal amount of shares that it covers and valid for a maximum period of five years, each as specified in the articles of association or relevant shareholder resolution. 96 Table of contents 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).
Biggest changeWe 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). 99 Table of contents English law also generally provides shareholders with preemptive rights when new shares are issued for cash.
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.
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.
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 the ordinary course of business, we transfer personal data from Europe and other jurisdictions to the United States or other countries. Europe and other jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries.
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.
We may enter into agreements with third parties to develop our commercial infrastructure for the sale of AUCATZYL and the commercial launch and continued sale of 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.
Additionally, HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in U.S. federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions; • the FDCA, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; • the U.S. 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; • 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; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or to adopt compliance programs as prescribed by state laws and regulations, or that otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; state and local laws that require the registration of pharmaceutical sales representatives; 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; and • 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 U.K.
Additionally, HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in U.S. federal courts to enforce HIPAA and seek attorneys’ fees and costs associated with pursuing federal civil actions; • the FDCA, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices; • the U.S. 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; 80 Table of contents • 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; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or to adopt compliance programs as prescribed by state laws and regulations, or that otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures; state and local laws that require the registration of pharmaceutical sales representatives; 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; and • 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 U.K.
Accordingly, our future results could be harmed by a variety of factors, including: • economic weakness, including inflation, or political instability in particular non-U.S. economies and markets; • differing and changing regulatory requirements for product approvals; • differing jurisdictions could present different issues for securing, maintaining or obtaining freedom to operate in such jurisdictions; • potentially reduced protection for intellectual property rights; • 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 U.S. and non-U.S. regulations and customs, tariffs and trade barriers; • changes in non-U.S. currency exchange rates of the pound sterling, U.S. dollar, euro and currency controls; • 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; • differing reimbursement regimes and price controls in certain non-U.S. markets; • negative consequences from changes in tax laws; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad, including, for example, the variable tax treatment in different jurisdictions of options granted under our share option schemes or equity incentive plans; • workforce uncertainty in countries where labor unrest is more common than in the United States; • 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; • difficulties associated with staffing and managing international operations, including differing labor relations; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • 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.
Accordingly, our future results could be harmed by a variety of factors, including: • economic weakness, including inflation, or political instability in particular non-U.S. economies and markets; • differing and changing regulatory requirements for product approvals; • differing jurisdictions could present different issues for securing, maintaining or obtaining freedom to operate in such jurisdictions; • potentially reduced protection for intellectual property rights; • 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 U.S. and non-U.S. regulations and customs, tariffs and trade barriers; 64 Table of contents • changes in non-U.S. currency exchange rates of the pound sterling, U.S. dollar, euro and currency controls; • 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; • differing reimbursement regimes and price controls in certain non-U.S. markets; • negative consequences from changes in tax laws; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad, including, for example, the variable tax treatment in different jurisdictions of options granted under our share option schemes or equity incentive plans; • workforce uncertainty in countries where labor unrest is more common than in the United States; • 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; • difficulties associated with staffing and managing international operations, including differing labor relations; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; and • 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.
Any potential acquisition or strategic collaboration, such as the Blackstone Collaboration Agreement and the BioNTech License Agreement, may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption of additional indebtedness or contingent liabilities; • negative covenants that may affect our ability to develop and commercialize our product candidates; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing programs and initiatives in pursuing such a strategic partnership, merger or acquisition; • retention of key employees, the loss of key personnel and uncertainties in our ability to maintain key business relationships; • risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and • our inability to generate revenue from acquired technology sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs. 65 Table of contents Additionally, if we undertake acquisitions, we may issue dilutive securities, assume or incur debt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expenses.
Any potential acquisition or strategic collaboration, such as the Blackstone Collaboration Agreement and the BioNTech License Agreement, may entail numerous risks, including: • increased operating expenses and cash requirements; • the assumption of additional indebtedness or contingent liabilities; • negative covenants that may affect our ability to develop and commercialize our product candidates; • assimilation of operations, intellectual property and products of an acquired company, including difficulties associated with integrating new personnel; • the diversion of our management’s attention from our existing programs and initiatives in pursuing such a strategic partnership, merger or acquisition; • retention of key employees, the loss of key personnel and uncertainties in our ability to maintain key business relationships; • risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and • our inability to generate revenue from acquired technology sufficient to meet our objectives in undertaking the acquisition or even to offset the associated acquisition and maintenance costs. 66 Table of contents Additionally, if we undertake acquisitions, we may issue dilutive securities, assume or incur debt obligations, incur large one-time expenses and acquire intangible assets that could result in significant future amortization expenses.
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; • positive or negative results from, or delays in, testing and clinical trials by us, collaborators or competitors; • the loss of any of our key scientific or management personnel; • 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 programs; • changes to our relationships with collaborators, manufacturers or suppliers; • 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; • actual or anticipated fluctuations in our operating results; • changes in financial estimates or recommendations by securities analysts; • potential acquisitions, financing, collaborations or other corporate transactions; • the results of our efforts to discover, develop, acquire or in-license additional product candidates; • the trading volume of our ADSs on Nasdaq; • 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 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; and • other events and factors, many of which are beyond our control.
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; • positive or negative results from, or delays in, testing and clinical trials by us, collaborators or competitors; • the loss of any of our key scientific or management personnel; • 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 programs; • changes to our relationships with collaborators, manufacturers or suppliers; • 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; • actual or anticipated fluctuations in our operating results; 93 Table of contents • changes in financial estimates or recommendations by securities analysts; • potential acquisitions, financing, collaborations or other corporate transactions; • the results of our efforts to discover, develop, acquire or in-license additional product candidates; • the trading volume of our ADSs on Nasdaq; • 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 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; and • other events and factors, many of which are beyond our control.
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.
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 have in the past and may in the future 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.
Further, pharmaceutical manufacturers can be held liable under the U.S. federal False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims; 78 Table of contents • HIPAA, which created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of whether the payor is public or private, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters; • HIPAA, as amended by HITECH, and their respective implementing regulations, which impose obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, and their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.
Further, pharmaceutical manufacturers can be held liable under the U.S. federal False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims; • HIPAA, which created new federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or obtain, by means of false or fraudulent pretenses, representations or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of whether the payor is public or private, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters; • HIPAA, as amended by HITECH, and their respective implementing regulations, which impose obligations on “covered entities,” including certain healthcare providers, health plans, and healthcare clearinghouses, as well as their respective “business associates” that create, receive, maintain or transmit individually identifiable health information for or on behalf of a covered entity, and their covered subcontractors, with respect to safeguarding the privacy, security and transmission of individually identifiable health information.
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.
Although there are currently various mechanisms that may be used to transfer personal data from the EEA, the U.K., 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.
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 products and product candidates.
Any uncured, material breach under the UCLB 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 products and product candidates.
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.
If we are unable to maintain favorable pricing and reimbursement status in EU Member States for our products and 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 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; 49 Table of contents • 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; and • the effectiveness of our sales and marketing efforts and distribution support.
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; and • the effectiveness of our sales and marketing efforts and distribution support.
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.
For example, we have been the target of unsuccessful phishing attempts in the past, and expect such attempts will continue in the future. Additionally, 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.
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.
To continue 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.
To the extent that the results of the trials are not satisfactory for the FDA, the EMA, the European Commission, or regulatory authorities in other countries or jurisdiction to approve our BLA, MAA, or other comparable application, the commercialization of our product candidates may be significantly delayed, or we may be required to expend significant additional resources, which may not be available to us, to conduct additional trials in support of potential approval of our product candidates. 59 Table of contents 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.
To the extent that the results of the trials are not satisfactory for the FDA, the EMA, the European Commission, or regulatory authorities in other countries or jurisdiction to approve our BLA, MAA, or other comparable application, the commercialization of our product candidates may be significantly delayed, or we may be required to expend significant additional resources, which may not be available to us, to conduct additional trials in support of potential approval of our product candidates. 61 Table of contents 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 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, 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; • the costs of hiring additional clinical, quality control and manufacturing personnel; • the costs, timing and outcome of regulatory review of our product candidates; • 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; and • the costs of operating as a public company.
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, 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; • the costs of hiring additional clinical, quality control and manufacturing personnel; 49 Table of contents • the costs, timing and outcome of regulatory review of our product candidates; • 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; and • the costs of operating as a public company.
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.
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 contractual obligations related to data privacy and security, and our efforts to comply with such obligations may not be successful.
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.
In addition, some companies, such as Cellectis, Inc., Les Laboratoires Servier SAS, Allogene Therapeutics Inc., Lyell Immunopharma and Crispr Therapeutics AG are pursuing allogenic T cell products that could compete with our programmed T cell product candidates.
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. 57 Table of contents 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.
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. 59 Table of contents 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.
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. 60 Table of contents 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.
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. 62 Table of contents 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.
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. There is no assurance that we will obtain breakthrough therapy designation or RMAT designation, or that we will obtain access to PRIME or ILAP for any of our product candidates.
We intend to seek breakthrough therapy designation, ILAP or PRIME designation for some or all of our programmed T cell product candidates that may qualify. There is no assurance that we will obtain breakthrough therapy designation, or that we will obtain access to PRIME or ILAP for any of our product candidates.
Future growth will impose significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining and motivating additional employees; • managing our internal development efforts effectively, including the clinical, FDA and EMA review processes for our product candidates; and • improving our operational, financial and management controls, reporting systems and procedures. 64 Table of contents There are a small number of individuals with experience in cell therapy and the competition for these individuals is high.
Future growth will impose significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining and motivating additional employees; • managing our internal development efforts effectively, including the clinical, FDA and EMA review processes for our product candidates; and • improving our operational, financial and management controls, reporting systems and procedures. 65 Table of contents There are a small number of individuals with experience in cell therapy and the competition for these individuals is high.
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.
Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and lawsuits. If we are unable to use AI, it could make our business less efficient and result in competitive disadvantages.
Even if the deaths are not related to our product candidate, the deaths could affect perceptions regarding the safety of our product candidate. 58 Table of contents Patient deaths and severe side effects caused by our product candidates, or by products or product candidates of other companies that are thought to have similarities with our therapeutic candidates, could result in the delay, suspension, clinical hold or termination of clinical trials by us, the FDA, the competent authorities of EU Member States or other regulatory authorities for a number of reasons.
Even if the deaths are not related to our product candidate, the deaths could affect perceptions regarding the safety of our product candidate. 60 Table of contents Patient deaths and severe side effects caused by our product candidates, or by products or product candidates of other companies that are thought to have similarities with our therapeutic candidates, could result in the delay, suspension, clinical hold or termination of clinical trials by us, the FDA, the competent authorities of EU Member States or other regulatory authorities for a number of reasons.
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.
Even though we have received FDA, MHRA and EU Commission 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 MHRA, 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 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 to effectively continue to train our field 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.
As a result, we cannot be sure that we will be able to submit INDs or similar applications for our preclinical programs on the timelines we expect, if at all, and we cannot be sure that submission of INDs or similar applications will result in the FDA, the competent authorities of EU Member States or other regulatory authorities allowing clinical trials to begin. 56 Table of contents Clinical trials are difficult to design and implement, involve uncertain outcomes and may not be successful.
As a result, we cannot be sure that we will be able to submit INDs or similar applications for our preclinical programs on the timelines we expect, if at all, and we cannot be sure that submission of INDs or similar applications will result in the FDA, the competent authorities of EU Member States or other regulatory authorities allowing clinical trials to begin. 58 Table of contents Clinical trials are difficult to design and implement, involve uncertain outcomes and may not be successful.
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.
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.
If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate. 61 Table of contents We plan to seek, but may fail to obtain breakthrough therapy designation or RMAT designation from the FDA and PRIME designation from the EMA, and may pursue accelerated approval for some or all of our programmed T cell product candidates, which may prolong the regulatory approval process for our product candidates.
If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in cases in which it would have been more advantageous for us to retain sole development and commercialization rights to such product candidate. 63 Table of contents We plan to seek, but may fail to obtain breakthrough therapy designation from the FDA and PRIME designation from the EMA, and may pursue accelerated approval for some or all of our programmed T cell product candidates, which may prolong the regulatory approval process for our product candidates.
The success in the development of our programmed T cell product candidates will depend on many factors, including: • completing preclinical studies and receiving regulatory approvals or clearance for conducting clinical trials for our preclinical-stage programs; • obtaining positive results in our clinical trials demonstrating efficacy, safety, and durability of effect of our product candidates; • establishing pediatric development plans with respect to product candidates for which we seek regulatory approval; • receiving approvals for commercialization of our product candidates from regulatory authorities; • manufacturing our product candidates at an acceptable cost; and • maintaining and growing an organization of scientists, medical professionals and business people who can develop and commercialize our products and technology.
The success in the development of our programmed T cell product candidates will depend on many factors, including: • completing preclinical studies and receiving regulatory approvals or clearance for conducting clinical trials for our preclinical-stage programs; • obtaining positive results in our clinical trials demonstrating efficacy, safety, and durability of effect of our product candidates; • establishing pediatric development plans with respect to product candidates for which we seek regulatory approval; • receiving approvals for commercialization of our product candidates from regulatory authorities; • manufacturing our product candidates at an acceptable cost; and 55 Table of contents • maintaining and growing an organization of scientists, medical professionals and business people who can develop and commercialize our products and technology.
If we lose our foreign private issuer status on this determination date, we would have to comply with U.S. federal proxy requirements, and our officers, directors and principal shareholders would become subject to the short-swing profit disclosure and recovery provisions of Section 16 of the Exchange Act.
If we lose our foreign private issuer status on this determination date, we would have to comply with U.S. federal proxy requirements, and our officers, directors and principal shareholders would become subject to the short-swing profit disclosure and recovery provisions contained in Section 16 of the Exchange Act.
You may face difficulties in protecting your interests, and your ability to protect your rights through the U.S. federal courts may be limited, because we are incorporated under the laws of England and Wales, conduct most of our operations outside the United States and most of our directors and senior management reside outside the United States.
You may face difficulties in protecting your interests, and your ability to protect your rights through the U.S. federal courts may be limited, because we are incorporated under the laws of England and Wales, conduct most of our operations outside the United States and most of our directors, and many members of our senior management, reside outside the United States.
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.
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 attacks, 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, telecommunications failures, earthquakes, fires, floods, attacks enhanced or facilitated by AI, and other similar threats.
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.
As of December 31, 2025, 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.
We filed a resale registration statement on Form S-3 to register the ADSs we sold to BioNTech in February 2024.
We filed a resale registration statement on Form S-3 to register the ADSs we sold to BioNTech in 2024.
The determination of foreign private issuer status is made annually on the last business day of an issuer’s most recently completed second fiscal quarter, and, accordingly, the next determination will be made with respect to us on June 30, 2025.
The determination of foreign private issuer status is made annually on the last business day of an issuer’s most recently completed second fiscal quarter, and, accordingly, the next determination will be made with respect to us on June 30, 2026.
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).
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”).
Federal and state enforcement bodies have continued their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of significant investigations, prosecutions, convictions and settlements in the healthcare industry. 79 Table of contents Efforts to ensure that our internal operations and future business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs.
Federal and state enforcement bodies have continued their scrutiny of interactions between healthcare companies and healthcare providers, which has led to a number of significant investigations, prosecutions, convictions and settlements in the healthcare industry. Efforts to ensure that our internal operations and future business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs.
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. 66 Table of contents While we have implemented security measures designed to protect against security incidents, there can be no assurance that these measures will be effective.
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.
Congress, the U.S. federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could weaken our ability to obtain patents or to enforce any patents that we might obtain in the future. 85 Table of contents We may not be aware of all third-party intellectual property rights potentially relating to our current and future our product candidates.
Congress, the U.S. federal courts, and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could weaken our ability to obtain patents or to enforce any patents that we might obtain in the future. We may not be aware of all third-party intellectual property rights potentially relating to our current and future our product candidates.
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. 50 Table of contents The incidence and prevalence for target patient populations for AUCATZYL and our other product candidates have not been established with precision.
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 these shares or ADSs are sold, or if it is perceived that they will be sold, in the public market, the trading price of our ADSs could decline. Our senior management, directors and principal shareholders, if they choose to act together, have the ability to control or significantly influence all matters submitted to our shareholders for approval.
If these shares or ADSs are sold, or if it is perceived that they will be sold, in the public market, the trading price of our ADSs could decline. 94 Table of contents Our senior management, directors and principal shareholders, if they choose to act together, have the ability to control or significantly influence all matters submitted to our shareholders for approval.
Licensing of intellectual property is of critical importance to our business and involves complex legal, business and scientific issues. For example, under our license agreement with UCLB, our exclusive rights under certain of the patents is subject to specified exclusions.
Licensing of intellectual property is of critical importance to our business and involves complex legal, business and scientific issues. For example, under the UCLB Agreement, our exclusive rights under certain of the patents is subject to specified exclusions.
We are incorporated and have our registered office in, and are currently existing under the laws of, England and Wales. In addition, most of our tangible assets are located, and most of our senior management and directors reside, outside of the United States.
We are incorporated and have our registered office in, and are currently existing under the laws of, England and Wales. In addition, most of our tangible assets are located outside of the United States, and most of our directors, and many members of our senior management, reside outside of the United States.
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.
Further, we have (and may in the future) experience 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.
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. 54 Table of contents Our future success is highly dependent on the regulatory approval of our other clinical-stage programmed T cell product candidates and our preclinical programs.
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 other clinical-stage programmed T cell product candidates and our preclinical programs.
The term ‘‘remuneration’’ has been broadly interpreted to include anything of value. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand.
The term “remuneration” has been broadly interpreted to include anything of value. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers on the other hand.
If one or more equity research analysts ceases coverage of us or fails to publish reports on us regularly, demand for our ADSs could decrease, which in turn could cause the trading price or trading volume of our ADSs to decline. Item 1B. Unresolved Staff Comments None. 97 Table of contents
If one or more equity research analysts ceases coverage of us or fails to publish reports on us regularly, demand for our ADSs could decrease, which in turn could cause the trading price or trading volume of our ADSs to decline. Item 1B. Unresolved Staff Comments None.
For example, HIPAA, as amended by the HITECH, imposes specific requirements relating to the privacy, security and transmission of protected health information. Additionally, in the past few years, numerous U.S. 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.
For example, HIPAA, as amended by HITECH, imposes specific requirements relating to the privacy, security and transmission of protected health information. Numerous U.S. 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.
We publish privacy policies, marketing materials, and other statements concerning data privacy and security.
We publish privacy policies, marketing materials, whitepapers, and other statements concerning data privacy and security.
Similar regulatory requirements apply outside the United States, including the International Council for Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (the “ICH”). 70 Table of contents Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors.
Similar regulatory requirements apply outside the United States, including the International Council for Harmonisation of Technical Requirements for the Registration of Pharmaceuticals for Human Use (the “ICH”). Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors.
Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. 74 Table of contents Securing marketing approval also requires the submission of information about the product manufacturing process demonstrating the products quality to, and inspection of manufacturing facilities by, the regulatory authorities.
Securing marketing approval requires the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each therapeutic indication to establish the product candidate’s safety and efficacy. Securing marketing approval also requires the submission of information about the product manufacturing process demonstrating the products quality to, and inspection of manufacturing facilities by, the regulatory authorities.
In addition, the stock market in general, and biopharmaceutical companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. 90 Table of contents Some companies that have experienced volatility in the trading price of their securities have been the subject of securities class action litigation.
In addition, the stock market in general, and biopharmaceutical companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance of these companies. Some companies that have experienced volatility in the trading price of their securities have been the subject of securities class action litigation.
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. 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.
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. 97 Table of contents 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.
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.
Although we have received FDA, MHRA and EU Commission 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.
The extent and duration of the conflicts in Ukraine and Gaza, geopolitical tensions, record inflation and resulting market disruptions are impossible to predict but could be substantial. Any such disruptions may also magnify the impact of other risks we face.
The extent and duration of the conflicts in Ukraine, and the Middle East, geopolitical tensions, record inflation and resulting market disruptions are impossible to predict but could be substantial. Any such disruptions may also magnify the impact of other risks we face.
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.
We are party to an exclusive intellectual property license agreement with UCLB (the “UCLB Agreement”), 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 expect to enter into additional license agreements in the future.
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. If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.
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. 84 Table of contents If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.
Similarly, a tax authority could assert that we are subject to tax in a jurisdiction where we believe we have not established a taxable connection, often referred to as a ‘‘permanent establishment’’ under international tax treaties, and such an assertion, if successful, could increase our expected tax liability in one or more jurisdictions.
Similarly, a tax authority could assert that we are subject to tax in a jurisdiction where we believe we have not established a taxable connection, often referred to as a “permanent establishment” under international tax treaties, and such an assertion, if successful, could increase our expected tax liability in one or more jurisdictions.
For example, the U.S. government has threatened to impose new tariffs on imported products from various foreign countries.
For example, the U.S. government has threatened to impose new and increased tariffs on imported products from various foreign countries.
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.
Under the BioNTech License Agreement, 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.
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. Our existing trademarks and any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business.
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. 91 Table of contents Our existing trademarks and any trademarks we may obtain may be infringed or successfully challenged, resulting in harm to our business.
These products may compete with our product candidates and preclinical programs and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
These products may compete with our product candidates and preclinical programs and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. 92 Table of contents Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
These current or future laws and regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. 83 Table of contents We previously identified material weaknesses in our internal control over financial reporting.
These current or future laws and regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions. We previously identified material weaknesses in our internal control over financial reporting.
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.
Even though we have been granted marketing approval by the FDA, MHRA and EU Commission 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 Risk Evaluation and Mitigation Strategy 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.
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. 82 Table of contents We are subject to the U.K.
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.
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.
However, despite these efforts, 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.
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.
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 reduced tax rate.
We do not maintain ‘‘key person’’ insurance for any of our employees. Recruiting and retaining qualified scientific and clinical personnel and, if we progress the development of any of our product candidates, commercialization, manufacturing and sales and marketing personnel, will be critical to our success.
We do not maintain “key person” insurance for any of our employees. Recruiting and retaining qualified scientific and clinical personnel and, if we progress the development of any of our product candidates, commercialization, manufacturing and sales and marketing personnel, will be critical to our success.
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. We are exposed to the risk of employee fraud or other misconduct or failure to comply with applicable regulatory requirements.
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. We are exposed to the risk of employee fraud or other misconduct or failure to comply with applicable regulatory requirements.
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.
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.
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.
Additionally, we filed two “resale” registration statements on Form F-3 under the Securities Act in 2022, followed by a resale registration statement on Form S-1 under the Securities Act in 2025, 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.
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 employees and personnel use generative AI technologies and/or automated decision-making technologies to perform their work, and the disclosure and use of personal data in AI technologies is subject to various privacy laws and other privacy obligations. Governments have passed and are likely to pass additional laws and regulations regulating AI or automated decision-making technologies.
Our failure to comply with all regulatory requirements, and later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, may yield various results, including: • litigation involving patients taking our products; • restrictions on such products, manufacturers or manufacturing processes; • restrictions on the labeling or marketing of a product; • restrictions on product distribution or use; • requirements to conduct post-marketing studies or clinical trials; • warning or untitled letters; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • recall of products; • fines, restitution or disgorgement of profits or revenues; • suspension, variation or withdrawal of marketing approvals; 76 Table of contents • suspension of any ongoing clinical trials; • damage to relationships with any potential collaborators; • unfavorable press coverage and damage to our reputation; • refusal to permit the import or export of our products; • product seizure; or • injunctions or the imposition of civil or criminal penalties.
Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU. 77 Table of contents Our failure to comply with all regulatory requirements, and later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, may yield various results, including: • litigation involving patients taking our products; • restrictions on such products, manufacturers or manufacturing processes; • restrictions on the labeling or marketing of a product; • restrictions on product distribution or use; • requirements to conduct post-marketing studies or clinical trials; • warning or untitled letters; • withdrawal of the products from the market; • refusal to approve pending applications or supplements to approved applications that we submit; • recall of products; • fines, restitution or disgorgement of profits or revenues; • suspension, variation or withdrawal of marketing approvals; • suspension of any ongoing clinical trials; • damage to relationships with any potential collaborators; • unfavorable press coverage and damage to our reputation; • refusal to permit the import or export of our products; • product seizure; or • injunctions or the imposition of civil or criminal penalties.
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 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, 2025, we had 754 employees, 752 of whom are full-time.
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.
While we have established a process which, to date, has proven 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.
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.
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 received FDA, MHRA and EU Commission approval in r/r B-ALL.
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.
For example, even though the FDA, MHRA and EU Commission granted marketing approval for AUCATZYL 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.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeThe information security function identifies and assesses risks from cybersecurity threats by monitoring and evaluating our threat environment and our risk profile using various methods including, for example, manual tools and automated tools, conducting scans of the threat environment, evaluating our and our industry’s risk profile, evaluating threats reported to us, internal and external audits, leveraging third party threat assessments, and conducting vulnerabilities assessments.
Biggest changeCybersecurity Risk management and strategy Our information security function is led by our Chief Information Officer, whose team is responsible for leading enterprise-wide cybersecurity strategy, policy, standards, architecture, and processes. 100 Table of contents The information security function identifies and assesses risks from cybersecurity threats by monitoring and evaluating our threat environment and our risk profile using various methods including, for example, manual tools and automated tools, conducting scans of the threat environment, evaluating our and our industry’s risk profile, evaluating threats reported to us, internal and external audits, leveraging third party threat assessments, and conducting vulnerabilities assessments.
The board and Audit Committee are responsible for ensuring that management has policies and processes in place designed to identify, monitor, assess and respond to cybersecurity, data privacy and other information technology risks to which the Company is exposed and implement processes and programs to manage cybersecurity risks and mitigate cybersecurity threats and incidents. 98 Table of contents
The board and Audit Committee are responsible for ensuring that management has policies and processes in place designed to identify, monitor, assess and respond to cybersecurity, data privacy and other information technology risks to which the Company is exposed and implement processes and programs to manage cybersecurity risks and mitigate cybersecurity threats and incidents. 101 Table of contents
Removed
Item 1C. Cybersecurity Risk management and strategy Our information security function is led by our Chief Information Officer, whose team is responsible for leading enterprise-wide cybersecurity strategy, policy, standards, architecture, and processes.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeOn February 27, 2020, we terminated the sublease of this office space and concurrently entered into a direct lease with the building owner for the same premises. The lease terminated at the end of February 2025. In February 2019, we entered into a lease for a manufacturing facility, consisting of approximately 39,558 square feet, in Enfield, U.K..
Biggest changeIn September 2024, the Company extended the lease term for Module 4 from August 2024 to December 2026; the Company currently uses this space for clinical manufacturing activities. In February 2019, we entered into a lease for a manufacturing facility, consisting of approximately 39,558 square feet, in Enfield, U.K..
In September 2021, we entered into an arrangement for lease with Forge Life Sciences Nominee ("Landlord"), an affiliate of the Reef Group, for the design, construction and lease of a new 70,000 square foot commercial manufacturing facility in Stevenage, U.K..
In September 2021, we entered into an arrangement for lease with Forge Life Sciences Nominee (“Landlord”), an affiliate of the Reef Group, for the design, construction and lease of a new 70,000 square foot commercial manufacturing facility in Stevenage, U.K..
In September 2021, we also entered into a lease agreement for 2,762 square feet of laboratory and office space in Gaithersburg, Maryland, with a term until March 2024. In September 2023, we extended the original lease term to March 2027.
In September 2021, we also entered into a lease agreement for 2,762 square feet of laboratory and office space in Gaithersburg, Maryland, with a term until March 2024. In September 2023, we extended the original lease term to March 2027. In November 2025, we decommissioned the laboratory space but continue to use the office space.
In addition, we have the option to terminate the lease in November 2026. Since September 2017, the Company has had an arrangement with Cell Therapy Catapult Limited to lease manufacturing suites at the Cell and Gene Therapy Catapult manufacturing center in Stevenage, United Kingdom.
Since September 2017, the Company has had an arrangement with Cell Therapy Catapult Limited to lease manufacturing suites at the Cell and Gene Therapy Catapult manufacturing center in Stevenage, United Kingdom.
In March 2023, the Company and Cell Therapy Catapult Limited mutually agreed: (i) to terminate the lease relating to the leased manufacturing suite which originally had a lease term until February 2025, (ii) to extend the lease term of one of the remaining manufacturing suites from June 2023 to August 2024, and (iii) to extend the lease term of a third manufacturing suite leased by the Company from September 2023 to August 2024.
In March 2023, the parties mutually agreed: (i) to terminate the lease relating to a leased manufacturing suite (known as Module 7) which originally had a lease term until February 2025, (ii) to extend the lease term of Module 3, one of the remaining manufacturing suites, from June 2023 to August 2024, and (iii) to extend the lease term of Module 4 a third manufacturing suite leased by the Company from September 2023 to August 2024.
In addition, during the year ended December 31, 2023, the Company recognized a loss on disposal on leasehold improvements of $3.8 million arising from the manufacturing suite terminated and exited on March 31, 2023. In August 2024, one of the manufacturing suite leases ended and the Company exited the suite.
In addition, during the year ended December 31, 2023, the Company recognized a loss on disposal on leasehold improvements of $3.8 million arising from the lease termination of Module 7 on March 31, 2023. In August 2024, the lease term for Module 3 ended and the Company vacated the suite.
During November 2023, we vacated this facility and relocated to The Nucleus. The current lease expires in October 2025. We anticipate leasing additional office and manufacturing space as we add employees, and we believe that suitable additional or substitute space will be available as needed to accommodate any such expansion of our operations. Item 3. Legal Proceedings None. Item 4.
We anticipate leasing additional office and manufacturing space as we add employees, and we believe that suitable additional or substitute space will be available as needed to accommodate any such expansion of our operations. Item 3. Legal Proceedings None. Item 4. Mine Safety Disclosure Not applicable 102 Table of contents PART II
The deed of variation does not affect the lease term, which continues to run for 20 years from September 19, 2023. The Nucleus will have a GMP cell manufacturing capacity of approximately 2,000 batches a year. We anticipate that the size and layout of the Nucleus will allow for further increases in this capacity.
However, the deed of variation provides for enhanced rental payments according to a specified formula, commencing in December 2025. The Nucleus will have a GMP cell manufacturing capacity of approximately 2,000 batches a year. We anticipate that the size and layout of the Nucleus will allow for further increases in this capacity.
Funding received for the Works done are deemed lease incentives in accordance to ASC 842. Once the Works are complete, the rental payments under the lease will be increased according to a specified formula for the remainder of the lease term.
Funding received for the Works done are deemed lease incentives in accordance with ASC Topic 842, Leases . The main Works will complete in March 2026. The deed of variation does not affect the lease term, which continues to run for 20 years from September 19, 2023.
Removed
In September 2024, the Company extended the lease term from August 2024 to March 2025 for the remaining manufacturing suite. In October 2018, we entered into a sublease for 27,502 square feet of office space in Rockville, Maryland.
Added
In addition, in January 2026, we entered into an amendment to the lease agreement that extended the lease term into November 2035. The amendment provides certain rent-free and reduced rent periods as an incentive, and includes a break window during which the Company may terminate the lease early in exchange for payment of a pre-specified rent penalty.
Removed
In order to commence the scale up of our manufacturing capability, an administrative office and training facility was set up at Unit 10, Gateway 1000, Arlington Business Park in Stevenage, U.K. adjacent to the Catapult facility. This office and training space was used to support the fit out and commencement of manufacturing activities at the Nucleus facility.
Added
We also lease shared office facilities in Weil Am Rhein, Germany, and Basel, Switzerland. The German lease runs through March 2027, and the Swiss lease through October 2027. Each lease will automatically renew if we do not provide notice of termination in accordance with the applicable terms.
Removed
Mine Safety Disclosure Not applicable 99 Table of contents PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeStockholders As of March 19, 2025, we had approximately 33 holders of record of our ordinary shares (including shares in the form of ADSs).
Biggest changeStockholders As of March 26, 2026, we had approximately 31 holders of record of our ordinary shares (including shares in the form of ADSs).
Sales of Unregistered Securities Except as disclosed in our previous filings with the SEC, we did not sell any unregistered securities during the year ended December 31, 2024. Issuer Purchases of Equity Securities We did not repurchase any of our equity securities during the year ended December 31, 2024.
Sales of Unregistered Securities Except as disclosed in our previous filings with the SEC, we did not sell any unregistered securities during the year ended December 31, 2025. Issuer Purchases of Equity Securities We did not repurchase any of our equity securities during the year ended December 31, 2025.
The following graph compares the cumulative total shareholder return on our ADSs with that of the Nasdaq Biotechnology Index (“NBI”) and Nasdaq 100 Index for the five years ended December 31, 2024.
The following graph compares the cumulative total shareholder return on our ADSs with that of the Nasdaq Biotechnology Index (“NBI”) and Nasdaq 100 Index for the five years ended December 31, 2025.
The NBI has been chosen as an appropriate comparator as it comprises similar companies to us in the pharmaceuticals and biotechnology sectors. 100 Table of contents Item 6. [Reserved]
The NBI has been chosen as an appropriate comparator as it comprises similar companies to us in the pharmaceuticals and biotechnology sectors. 103 Table of contents Item 6. [Reserved]

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeIt also consisted of direct production costs relating to commercial product manufactured, and allocated facility costs including maintenance, depreciation, utilities and rent. 109 Table of contents Research and Development Expenses The following tables provide additional detail on our R&D expenses (in thousands): Year Ended December 31, Change (in thousands) Change (in percentage) 2024 2023 Direct research and development expenses B cell malignancies (Obe-cel, AUTO1/22 & AUTO3) $ 24,370 $ 22,855 $ 1,515 7 % Other projects (AUTO4, AUTO5, AUTO6, AUTO7 & AUTO8) 2,003 3,098 (1,095) (35) % Total direct research and development expense 26,373 25,953 420 2 % Research and development expense and unallocated costs: Personnel related (including share-based compensation) 74,329 63,542 10,787 17 % Indirect research and development expense* 37,734 40,986 (3,252) (8) % Total research and development expenses $ 138,436 $ 130,481 $ 7,955 6 % * Indirect research and development expense includes U.K. research and development tax credits Research and development expenses increased by $7.9 million to $138.4 million for the year ended December 31, 2024 from $130.5 million for the year ended December 31, 2023 primarily due to: • an increase of $12.0 million in salaries and other employment related costs including share-based compensation expense, which was mainly driven by an increase in the number of employees engaged in research and development activities; • an increase of $3.6 million in clinical trial costs, manufacturing costs and material transportation costs relating to research and development activities; • a decrease of $5.2 million in legal fees and professional consulting fees in relation to our research and development activities; • a decrease of $2.2 million related to our information technology infrastructure and support for information systems related to our research and development activities and facilities offset by an increase in depreciation and amortization related to property and equipment; and • an increase of $0.3 million in U.K.
Biggest changeResearch and Development Expenses, Net The following tables provide additional detail on our R&D expenses (in thousands): Year Ended December 31, Change (in thousands) Change (in percentage) 2025 2024 Direct research and development expenses B cell malignancies (Obe-cel & AUTO1/22) $ 38,177 $ 24,370 $ 13,807 57 % Other projects (AUTO4, AUTO5, AUTO6, AUTO7 & AUTO8) 2,592 2,003 589 29 % Total direct research and development expense 40,769 26,373 14,396 55 % Indirect research and development expenses and unallocated costs: Personnel related (including share-based compensation) 57,269 74,329 (17,060) (23) % Indirect research and development expense* 19,651 37,734 (18,083) (48) % Total Research and Development Expenses, Net $ 117,689 $ 138,436 $ (20,747) (15) % * Indirect research and development expense includes U.K. research and development tax credits Research and development expenses, net decreased by $20.7 million to $117.7 million for the year ended December 31, 2025 from $138.4 million for the year ended December 31, 2024 primarily due to: • a decrease of $22.2 million related to our information technology infrastructure, support for information systems, facility costs and depreciation, including the allocation of expense from research and development to cost of sales and inventories related to commercial manufacturing following the FDA approval of AUCATZYL in November 2024; and • a decrease of $19.3 million in salaries and other employment related costs including share-based compensation expense, which was mainly driven by the reallocation of employees to commercial manufacturing activities included in cost of sales and inventories; offset by • a decrease of $15.1 million in U.K.
We believe our programmed T cell therapies have the potential to be best-in-class and offer patients substantial benefits over the existing standard of care, including the potential for cure in some patients. Since our inception, we have incurred significant operating losses.
We believe our programmed T cell therapies have the potential to be best-in-class and to offer patients substantial benefits over the existing standard of care, including the potential for cure in some patients. Since our inception, we have incurred significant operating losses.
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.
Qualifying expenditures largely comprise of 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.
Recently Issued Accounting Pronouncements A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2, “Summary of Significant Accounting Policies,” to our consolidated financial statements included in in this Annual Report.
Recently Issued Accounting Pronouncements A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2, “Summary of Significant Accounting Policies,” to our consolidated financial statements included in this Annual Report.
Our future funding requirements will depend on and could increase significantly as a result of many factors, including: • our ability to continue to execute our commercialization strategies for AUCATZYL and, if approved, our other product candidates; • the scope, progress, outcome and costs of our clinical trials and other research and development activities; • the costs, timing, receipt and terms of any marketing approvals from applicable regulatory authorities; • the costs of future activities, including product sales, medical affairs, marketing, manufacturing and distribution, for AUCATZYL or any of our product candidates for which we receive marketing approval; • the revenue, if any, received from commercial sale of AUCATZYL or our other product candidates, should any receive marketing approval; • the costs and timing of hiring new employees to support our continued growth; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; and • the extent to which we in-license or acquire additional product candidates or technologies.
Our future funding requirements will depend on and could increase significantly as a result of many factors, including: • our ability to continue to execute our commercialization strategies for AUCATZYL and, if approved, any of our other product candidates for which we may receive regulatory approval; • the scope, progress, outcome and costs of our clinical trials and other research and development activities; • the costs, timing, receipt and terms of any marketing approvals from applicable regulatory authorities; • the costs of future activities, including product sales, medical affairs, marketing, manufacturing and distribution, for AUCATZYL or any of our product candidates for which we receive marketing approval; • the revenue, if any, received from commercial sale of AUCATZYL or our other product candidates, should any receive marketing approval; • the costs and timing of hiring new employees to support our continued growth; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; and • the extent to which we in-license or acquire additional product candidates or technologies.
The forecast of cash resources is forward-looking information that involves risks and uncertainties, and the actual amount of our revenues and expenses, which we have based on assumptions that may prove to be wrong and could prove to be significantly higher than we currently anticipate, could vary materially and adversely as a result of a number of factors.
This forecast of cash resources is forward-looking information that involves risks and uncertainties, and the actual amount of our revenues and expenses, which we have based on assumptions that may prove to be wrong and could prove to be significantly higher than we currently anticipate, could vary materially and adversely as a result of a number of factors.
Our expenses will increase as we: • establish and expand our sales, marketing and distribution infrastructure in connection with commercializing AUCATZYL and other product candidates for which we may obtain marketing approval and intend to commercialize on our own or jointly; • seek regulatory approvals for any other product candidates that successfully complete preclinical and clinical trials; • hire additional manufacturing, clinical, medical and development personnel; • expand our infrastructure and facilities to accommodate our growing employee base; and • maintain, expand and protect our intellectual property portfolio. 112 Table of contents Our primary uses of capital are compensation and related expenses, clinical costs, external research and development services, laboratory and related supplies, legal and other regulatory expenses, and administrative and overhead costs.
Our expenses will increase as we: • establish and expand our sales, marketing and distribution infrastructure in connection with commercializing AUCATZYL and other product candidates for which we may obtain marketing approval and intend to commercialize on our own or jointly; • seek regulatory approvals for any other product candidates that successfully complete preclinical and clinical trials; • hire additional manufacturing, clinical, medical and development personnel; • expand our infrastructure and facilities to accommodate our growing employee base; and • maintain, expand and protect our intellectual property portfolio. 116 Table of contents Our primary uses of capital are compensation and related expenses, clinical costs, external research and development services, laboratory and related supplies, legal and other regulatory expenses, and administrative and overhead costs.
We have experienced, and expect to continue to experience, increased expense with being a public company, including increased accounting, audit, legal, regulatory and compliance costs associated with maintaining compliance with Nasdaq listing rules and SEC requirements, director and officer insurance premiums, as well as higher investor and public relations costs.
We have experienced, and expect to continue to experience, increased expense with being a public company, including increased accounting, audit, legal, regulatory and compliance costs associated with maintaining compliance with Nasdaq listing rules and the SEC requirements, director and officer insurance premiums, as well as higher investor and public relations costs.
Included in general and administrative expenses is historical irrecoverable input VAT previously claimed on general and administrative expenses and subsequently reversed. We anticipate that our general and administrative expenses will increase in the future as we increase our headcount to support the planned development of our product candidates.
Included in selling, general and administrative expenses is historical irrecoverable input VAT previously claimed on selling, general and administrative expenses and subsequently reversed. We anticipate that our selling, general and administrative expenses will increase in the future as we increase our headcount to support the planned development of our product candidates.
Net Cash Used In Investing Activities During the year ended December 31, 2024, we used $394.5 million of cash in investing activities, including purchases of marketable securities of $359.7 million, purchases of property and equipment of $22.1 million, and acquisition of intangible assets of $12.7 million.
During the year ended December 31, 2024, we used $394.5 million of cash in investing activities, including purchases of marketable securities of $359.7 million, purchases of property and equipment of $22.1 million, and acquisition of intangible assets of $12.7 million.
While our significant accounting policies are described in more detail in Note 2 to our consolidated financial statements included in this Annual Report, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our consolidated financial statements. 114 Table of contents Allocation of transaction price using the relative standalone selling price Upfront payments are allocated between performance obligations using our best estimate of the relative standalone selling price of the performance obligation.
While our significant accounting policies are described in more detail in Note 2 to our consolidated financial statements included in this Annual Report, we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our consolidated financial statements. 118 Table of contents Allocation of transaction price using the relative standalone selling price Upfront payments are allocated between performance obligations using our best estimate of the relative standalone selling price of the performance obligation.
Contingent Research Milestone Payments ASC Topic 606 constrains the amount of variable consideration included in the transaction price in that either all, or a portion, of an amount of variable consideration should be included in the transaction price.
Contingent Research Milestone Payments ASC 606 constrains the amount of variable consideration included in the transaction price in that either all, or a portion, of an amount of variable consideration should be included in the transaction price.
Net Cash Provided By (Used In) Financing Activities During the year ended December 31, 2024, net cash provided financing activities was $589.6 million related to net aggregate proceeds raised from the BioNTech Agreements, our underwritten offering of ADSs and a Blackstone Development Payment paid by Blackstone to us upon the FDA approval of AUCATZYL.
During the year ended December 31, 2024, net cash provided by financing activities was $589.6 million related to net aggregate proceeds raised from the BioNTech Agreements, our underwritten offering of ADSs and a Blackstone Development Payment paid by Blackstone to us upon the FDA approval of AUCATZYL.
Further details of the Blackstone Collaboration Agreement are provided in Note 11 to our consolidated financial statements included in this Annual Report. BioNTech Collaboration Agreement Obe-cel Revenue Interest Under the BioNTech License Agreement, BioNTech has also agreed to financially support the expansion of the clinical development program and planned commercialization of obe-cel.
Further details of the Blackstone Collaboration Agreement are provided in Note 12 to our consolidated financial statements included in this Annual Report. BioNTech Collaboration Agreement Obe-cel Revenue Interest Under the BioNTech License Agreement, BioNTech has also agreed to financially support the expansion of the clinical development program and planned commercialization of obe-cel.
In exchange for the Blackstone Development Payments, we agreed to make payments to Blackstone (the “Revenue Share Payments”) equal to a mid-single digit royalty, subject to the Aggregate Cap (as defined in the Blackstone Collaboration Agreement) on payments under the Blackstone Collaboration Agreement, based on net sales anywhere in the world of (i) Collaboration Products in B-cell malignancies, (ii) subject to certain conditions set forth in the Blackstone Collaboration Agreement, its CD19 and CD22 CAR T cell investigational therapy product candidate known as AUTO3 in B-cell malignancies, and (iii) certain Collaboration Products to the extent developed or commercialized in indications other than a B-cell malignancy (“Obe-cel Franchise Products”).
In exchange for the Blackstone Development Payments, we agreed to make payments to Blackstone (the “Revenue Share Payments”) equal to a mid-single digit royalty, subject to the Aggregate Cap (as defined in the Blackstone Collaboration Agreement) on payments under the Blackstone Collaboration Agreement, based on net sales anywhere in the world of (i) Collaboration Products in B-cell malignancies, (ii) subject to certain conditions set forth in the Blackstone Collaboration Agreement, its CD19 and CD22 CAR T cell investigational therapy product candidate known as AUTO3 in B-cell malignancies, and (iii) certain Collaboration Products to the extent developed or commercialized in indications other than a B-cell malignancy.
An assessment of the allocation of transaction price using the relative standalone selling price was required for the year ended December 31, 2024 and 2023 for the BioNTech License and Option Agreement, the Research, Option and License Agreement with Cabaletta and Research, Option and License Agreement with an investee of Syncona Portfolio Limited , respectively.
An assessment of the allocation of transaction price using the relative standalone selling price was required for the year ended December 31, 2025 and 2024 for the BioNTech License and Option Agreement, the Research, Option and License Agreement with Cabaletta and Research, Option and License Agreement with an investee of Syncona Portfolio Limited , respectively.
These payments include (i) an upfront payment of $50.0 million and (ii) up to $100.0 million payable based on the achievement of certain specified clinical, manufacturing and regulatory milestones (each such payment, a “Blackstone Development Payment” and collectively, the “Blackstone Development Payments”) 103 Table of contents In November 2021, the upfront payment of $50.0 million was paid by Blackstone upon execution of the Blackstone Collaboration Agreement.
These payments include (i) an upfront payment of $50.0 million and (ii) up to $100.0 million payable based on the achievement of certain specified clinical, manufacturing and regulatory milestones (each such payment, a “Blackstone Development Payment” and collectively, the “Blackstone Development Payments”) In November 2021, the upfront payment of $50.0 million was paid by Blackstone upon execution of the Blackstone Collaboration Agreement.
Commercialization of our product candidates will take several years and millions of dollars in development costs. U.K. Research and Development Tax Credits Research and development expenditure is presented net of reimbursements from reimbursable tax and expenditure credits from the U.K. government.
Commercialization of our product candidates will take several years and millions of dollars in development costs. U.K. Research and Development Tax Credits Research and development expenditure is presented net of reimbursements from reimbursable tax and expenditure credits from the United Kingdom government.
Amendments to the current SME and RDEC programs contained in the Finance Act 2024 (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 U.K. or such workers are not subject to U.K. payroll taxes, and (ii) merge the SME and RDEC programs 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.
Amendments to the current SME and RDEC programs contained in the Finance Act 2024 (unless limited exceptions apply) introduce (i) restrictions on the tax relief that can be claimed for expenditure incurred on sub-contracted R&D activities or externally provided workers, where such activities are not carried out in the United Kingdom or such workers are not subject to United Kingdom payroll taxes, and (ii) merge the SME and RDEC programs 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.
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.
A large proportion of costs relate 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.
We are also obligated to make payments (the “Sales Milestone Payments”), subject to the Aggregate Cap, if certain cumulative net sales levels are achieved. In November 2021, the upfront payment of $50 million was paid by Blackstone upon execution of the Blackstone Collaboration Agreement.
We are also obligated to make payments, subject to the Aggregate Cap, if certain cumulative net sales levels are achieved. In November 2021, the upfront payment of $50 million was paid by Blackstone upon execution of the Blackstone Collaboration Agreement.
No deferred tax assets are recognized on our U.K. losses and tax credit carryforwards because there is currently no indication that we will make sufficient taxable profits to utilize these tax losses and tax credit carryforwards. We carry a $3.2 million deferred tax asset balance related to the U.S. entity at December 31, 2024.
No deferred tax assets are recognized on our U.K. losses and tax credit carryforwards because there is currently no indication that we will make sufficient taxable profits to utilize these tax losses and tax credit carryforwards. We carry a $3.6 million deferred tax asset balance related to the U.S. entity at December 31, 2025.
All references in this Annual Report to “$” are to U.S. dollars and all references to “£” are to pounds sterling. Our consolidated balance sheets as of December 31, 2024 and 2023 have been translated from pounds sterling into U.S. dollars at the rate of £1.00 to $1.2535 and £1.00 to $1.2730, respectively.
All references in this Annual Report to “$” are to U.S. dollars and all references to “£” are to pounds sterling. Our consolidated balance sheets as of December 31, 2025 and 2024 have been translated from pounds sterling into U.S. dollars at the rate of £1.00 to $1.3455 and £1.00 to $1.2535, respectively.
Included in research and development expenses is historical irrecoverable input VAT previously claimed on research and development expenses and subsequently reversed. The successful development and commercialization of our product candidates is highly uncertain.
Included in research and development expenses is historical irrecoverable input VAT previously claimed on research and development expenses and subsequently reversed. 110 Table of contents The successful development and commercialization of our product candidates is highly uncertain.
Our consolidated statements of operations and comprehensive loss and consolidated statements of cash flows for the years ended December 31, 2024 and 2023 have been translated from pounds sterling to U.S. dollars at the rate of £1.00 to $1.2779, £1.00 to $1.2433, respectively.
Our consolidated statements of operations and comprehensive loss and consolidated statements of cash flows for the years ended December 31, 2025 and 2024 have been translated from pounds sterling to U.S. dollars at the rate of £1.00 to $1.3181, £1.00 to $1.2779, respectively.
We have funded our operations to date primarily with proceeds from government grants, sales of our equity securities, through public offerings and pursuant to our at-the-equity market facility, through U.K. research and development tax credits and receipts from the SME and RDEC schemes, out-licensing arrangements and strategic collaboration and financing agreements.
We have funded our operations to date primarily with proceeds from government grants, sales of our equity securities including ADSs, through public offerings and pursuant to our at-the-market equity facility, through U.K. research and development tax credits and receipts from the SME and RDEC schemes, out-licensing arrangements, strategic collaboration agreements and sale of our commercial product.
Until such time, if ever, that we can generate product revenue sufficient to achieve profitability, we expect to finance our cash needs through a combination of public or private equity offerings, reimbursable U.K. research and development tax credits and receipts from the SME and RDEC schemes, out-licensing agreements, or strategic collaboration agreements.
Until such time, if ever, that we can generate product revenue sufficient to achieve profitability, we expect to finance our cash needs through a combination of public or private equity offerings, reimbursable United Kingdom research and development tax credits and receipts from the RDEC scheme, out-licensing agreements, or strategic collaboration agreements.
For example, if the European Medicines Agency (“EMA”), the FDA, or another regulatory authority were to delay our planned start of clinical trials or require us to conduct clinical trials or other testing beyond those that we currently expect or if we experience significant delays in enrollment in any of our planned clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development of that product candidate.
For example, if the European Medicines Agency (“EMA”), national competent authorities of EU Member States, as applicable, the FDA, the MHRA, or another regulatory authority were to delay our planned start of clinical trials or require us to conduct clinical trials or other testing beyond those that we currently expect or if we experience significant delays in enrollment in any of our planned clinical trials, we could be required to expend significant additional financial resources and time on the completion of clinical development of that product candidate.
Based on our current clinical development and commercialization plans, we believe our existing cash and cash equivalents of $227.4 million and available-for-sale debt securities of $360.6 million at December 31, 2024, will enable us to fund our current and planned operating expenses and capital expenditure requirements for at least twelve months from the issuance of this Annual Report.
Based on our current clinical development and commercialization plans, we believe our existing cash and cash equivalents of $104.1 million and available-for-sale debt securities of $196.6 million at December 31, 2025, will enable us to fund our current and planned operating expenses and capital expenditure requirements for at least twelve months from the issuance of this Annual Report.
During the year ended December 31, 2024, we entered into various license agreements which included non-refundable upfront license fees, options for future commercial licenses, payments based upon achievement of clinical development and regulatory objectives, payments based upon achievement of certain levels of product sales, and royalties on licensed product sales .
As of December 31, 2025, we have entered into various license agreements which included non-refundable upfront license fees, options for future commercial licenses, payments based upon achievement of clinical development and regulatory objectives, payments based upon achievement of certain levels of product sales, and royalties on licensed product sales .
Contractual Obligations Operating Lease, Purchase, and Other Obligations Operating leases As of December 31, 2024, we had operating lease obligations of $52.6 million under non-cancellable leases for laboratory and office property in the United Kingdom and the United States.
Contractual Obligations Operating Lease, Purchase, and Other Obligations Operating leases As of December 31, 2025, we had operating lease obligations of $71.4 million under non-cancellable leases for laboratory and office property in the United Kingdom and the United States.
We expect to incur the full amount of these obligations within one year. As of December 31, 2024 , our unconditional purchase obligations for reagents and disposables totaled $0.6 million, which we expect to incur within one year.
We expect to incur the full amount of these obligations within one year. As of December 31, 2025 , our unconditional purchase obligations for reagents and disposables totaled $1.7 million, which we expect to incur within one year.
Payments due upon cancellation consist only of payments for services provided or expenses incurred, including noncancellable obligations of our service providers, up to the date of cancellation. 113 Table of contents As of December 31, 2024, our unconditional purchase obligations for capital expenditures totaled $17.5 million and included signed orders for capital equipment and capital expenditure for construction and related expenditure relating to our properties in the U.K. and the United States.
Payments due upon cancellation consist only of payments for services provided or expenses incurred, including noncancellable obligations of our service providers, up to the date of cancellation. 117 Table of contents As of December 31, 2025, our unconditional purchase obligations for capital expenditures totaled $1.8 million and included signed orders for capital equipment and capital expenditure for construction and related expenditure relating to our properties in the United Kingdom.
Interest expense, net decreased by $35.8 million primarily due to changes in the assumptions used in the valuation of the Collaboration Agreement with Blackstone and the BioNTech License and Option Agreement for the year ended December 31, 2024 compared to the year ended December 31. 2023.
Interest expense, net increased by $27.4 million primarily due to changes in the assumptions used in the valuation of the Collaboration Agreement with Blackstone and the BioNTech License and Option Agreement for the year ended December 31, 2025 compared to the year ended December 31, 2024.
From our inception in 2014 through December 31, 2024 , we have raised an aggregate of $1.7 billion from these capital sources. As of December 31, 2024 , we had cash and cash equivalents on hand of $227.4 million and available-for-sale debt securities of $360.6 million.
From our inception in 2014 through December 31, 2025 , we have raised an aggregate of $1.8 billion from these capital sources. As of December 31, 2025 , we had cash and cash equivalents on hand of $104.1 million and available-for-sale debt securities of $196.6 million.
Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials.
Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and duration of later-stage clinical trials.
Based on our current commercial and development plans, we believe our existing cash and cash equivalents of $227.4 million and marketable securities of $360.6 million at December 31, 2024, will be sufficient to fund our current and planned operating expenses and capital expenditure requirements through at least the next twelve months from the date of this Annual Report.
Based on our current commercial and development plans, we believe our existing cash and cash equivalents of $104.1 million and available for sale debt securities ( “ marketable securities ” ) of $196.6 million at December 31, 2025, will be sufficient to fund our current and planned operating expenses and capital expenditure requirements through at least the next twelve months from the date of this Annual Report.
Interest Expense, Net Interest expense, net consists primarily of interest expense arising from amortization of the liabilities related to future royalties and milestones, pursuant to our collaboration agreements with Blackstone and BioNTech, using the effective interest rate method.
Interest Expense, Net Interest expense, net consists primarily of interest expense arising from amortization of the liabilities related to future royalties and milestones, pursuant to our collaboration agreements with BXLS V - Autobahn L.P, (“Blackstone”) and BioNTech SE (“BioNTech”), using the effective interest rate method.
Under the License Agreement, BioNTech is solely responsible for, and has sole decision-making authority with respect to, at its own expense, the exploitation of Binder Licensed Products. 102 Table of contents Under the terms of the License Agreement, we have agreed to grant BioNTech the following time-limited Options: • an option to obtain exclusive rights to co-fund development costs of our development-stage programs AUTO1/22 and AUTO6NG, in return for agreed upon economic terms, including an option exercise fee, milestone payments and a profit-sharing arrangement for each such product candidate, with additional options to co-promote or co-commercialize such product candidate.
Under the terms of the License Agreement, we have agreed to grant BioNTech the following time-limited Options: • an option to obtain exclusive rights to co-fund development costs of our development-stage programs AUTO1/22 and AUTO6NG, in return for agreed upon economic terms, including an option exercise fee, milestone payments and a profit-sharing arrangement for each such product candidate, with additional options to co-promote or co-commercialize such product candidate.
Milestone payments (“BioNTech Milestone Payments”) pursuant to the BioNTech License and Option Agreement are payable upon BioNTech's election, and therefore have not been included in the determination of the effective interest rate or in the measurement of the liability.
Milestone payments pursuant to the BioNTech License and Option Agreement are payable upon BioNTech's election, and therefore have not been included in the determination of the effective interest rate or in the measurement of the liability. The liabilities are amortized using the effective interest rate, resulting in recognition of interest expense over the estimated term of the agreement.
The assessment of whether variable consideration should be constrained is largely a qualitative one that has two elements: the likelihood of a change in estimate, and the magnitude thereof.
The assessment of whether variable consideration should be constrained is largely a qualitative one that has two elements: the likelihood of a change in estimate, and the magnitude thereof. Variable consideration is not constrained if the potential reversal of cumulative revenue recognized is not significant, for example.
To the extent the amount or timing of such receipts or payments is materially different than our previous estimates we record a cumulative catch-up adjustment to the liabilities related to future royalties and milestones. The adjustment to the carrying amount is recognized as an adjustment to interest expense in the period in which the change in estimate occurred.
To the extent the amount or timing of such receipts or payments is materially different than our previous estimates we record a cumulative catch-up adjustment to the liabilities related to future royalties and milestones.
Manufacturing and Commercial Agreement Under the terms of the License Agreement, we have granted BioNTech the option to negotiate a joint manufacturing and commercial services agreement pursuant to which we and they may access and leverage each other’s manufacturing and commercial capabilities, in addition to our commercial site network and infrastructure, with respect to certain of each parties’ CAR T products, including BioNTech’s product candidate BNT211 (the “Manufacturing and Commercial Agreement”).
During the year ended December 31, 2025, we made quarterly payments of the revenue interest to BioNTech in an aggregate amount of $1.5 million 106 Table of contents Manufacturing and Commercial Agreement Under the terms of the License Agreement, we have granted BioNTech the option to negotiate a joint manufacturing and commercial services agreement pursuant to which we and they may access and leverage each other’s manufacturing and commercial capabilities, in addition to our commercial site network and infrastructure, with respect to certain of each parties’ CAR T products, including BioNTech’s product candidate BNT211 (the “Manufacturing and Commercial Agreement”).
After consultation, we have been advised by HMRC that any 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, we have assessed and restricted the amount of U.K. VAT we have historically reclaimed and will continue to do so in the future.
After consultation, we have been advised by HMRC that any sale of our obe-cel CAR T therapy to United Kingdom customers in the future will be considered an exempt supply from a United Kingdom VAT perspective.
For the years ended December 31, 2024 and 2023, we incurred net losses of $220.7 million and $208.4 million, respectively. As of December 31, 2024, we had an accumulated deficit of $1,099.2 million.
For the years ended December 31, 2025 and 2024, we incurred net losses of $287.5 million and $220.7 million, respectively. As of December 31, 2025, we had an accumulated deficit of $1,386.8 million.
The consideration also can vary if our entitlement to the consideration is contingent on the occurrence or non-occurrence of a future event. We consider contingent research milestone payments to fall under the scope of variable consideration, which should be estimated for revenue recognition purposes at the inception of the contract and reassessed ongoing at the end of each reporting period.
We consider contingent research milestone payments to fall under the scope of variable consideration, which should be estimated for revenue recognition purposes at the inception of the contract and reassessed ongoing at the end of each reporting period.
Additionally, should we fail to maintain our status as a foreign private issuer, we would expect to incur increased expenses to remain compliant with applicable SEC and Nasdaq requirements. Loss on disposal of property and equipment Loss on disposal of property and equipment primarily consists of losses arising from the disposal of all categories of property and equipment.
Additionally, should we fail to maintain our status as a foreign private issuer, we would expect to incur increased expenses to remain compliant with the applicable SEC and Nasdaq requirements. Other Income, Net Other income, net consists primarily of sublease income and gains or losses arising from the termination of leases.
Interest Expense, Net Interest expense, net decreased to $9.3 million for the year ended December 31, 2024 as compared to $45.1 million for the year ended December 31, 2023.
Interest Expense, Net Interest expense, net increased to $36.7 million for the year ended December 31, 2025 as compared to $9.3 million for the year ended December 31, 2024.
The non-cash charges related to interest expense accrued and cumulative catch-up adjustment of $45.0 million, share-based compensation of $11.2 million, depreciation and amortization of $6.6 million, non-cash operating lease expense of $4.1 million, loss on disposal of leasehold improvements of $3.8 million, impairment of operating lease right-of-use assets and related property and equipment of $0.4 million and loss on termination of operating lease of $0.1 million which is partially offset by foreign exchange differences of $7.6 million and a deferred income tax movement of $1.0 million.
The non-cash charges related to interest expense accrued and cumulative catch-up adjustment of $36.4 million, share-based compensation of $14.4 million, inventory reserves and write-offs of $12.3 million, depreciation and amortization of $9.8 million and an impairment of operating lease right-of-use assets and related property and equipment of $0.3 million, which is offset by amortization of available-for-sale securities of $8.2 million, non-cash operating lease expense of $5.7 million, foreign exchange differences of $3.1 million and deferred income tax movement of $0.3 million.
Interest Income Interest income increased to $32.4 million for the year ended December 31, 2024, as compared to $13.5 million for the year ended December 31, 2023.
Interest Income Interest income decreased to $19.0 million for the year ended December 31, 2025, as compared to $32.4 million for the year ended December 31, 2024.
Cash Flows The following table summarizes our cash flows for each of the periods presented (in thousands): Year Ended December 31, 2024 2023 Net cash used in operating activities $ (206,271) $ (145,587) Net cash used in investing activities (394,552) (10,986) Net cash provided by (used in) financing activities 589,554 (883) Effect of exchange rate changes on cash, cash equivalents and restricted cash (261) 15,030 Net decrease in cash, cash equivalents and restricted cash $ (11,530) $ (142,426) 111 Table of contents Net Cash Used in Operating Activities During the year ended December 31, 2024, operating activities used $206.3 million of cash, resulting from our net loss of $220.7 million, and net cash used resulting from changes in our operating assets and liabilities of $23.6 million, partially offset by non-cash charges of $38.0 million.
Cash Flows The following table summarizes our cash flows for each of the periods presented (in thousands): Year Ended December 31, 2025 2024 Net cash used in operating activities $ (283,568) $ (206,271) Net cash provided by (used in) investing activities 158,458 (394,552) Net cash (used in) provided by financing activities (4,339) 589,554 Effect of exchange rate changes on cash, cash equivalents and restricted cash 6,279 (261) Net decrease in cash, cash equivalents and restricted cash $ (123,170) $ (11,530) 115 Table of contents Net Cash Used in Operating Activities During the year ended December 31, 2025, operating activities used $283.6 million of cash, resulting from our net loss of $287.5 million, and net cash used resulting from changes in our operating assets and liabilities of $52.0 million, partially offset by non-cash charges of $55.9 million.
In determining the appropriate amount of revenue to be recognized in relation to each license agreement, we perform the following steps: (i) identify the promised goods or services in the contract; (ii) determine whether the promised goods or services are performance obligations, including whether they are distinct in the context of the contract; (iii) measure of the transaction price, including the constraint on variable consideration; (iv) allocate the transaction price to the performance obligations based on estimated selling prices; and (v) recognize of revenue when (or as) we satisfy each performance obligation.
In determining the appropriate amount of revenue to be recognized in relation to each license agreement, we perform the following steps: (i) identify the promised goods or services in the contract; (ii) determine whether the promised goods or services are performance obligations, including whether they are distinct in the context of the contract; (iii) measure of the transaction price, including the constraint on variable consideration; (iv) allocate the transaction price to the performance obligations based on estimated selling prices; and (v) recognize of revenue when (or as) we satisfy each performance obligation. 108 Table of contents License Fees and Multiple Element Arrangements If a license to our intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, we recognize revenues from non-refundable, upfront fees allocated to the license at such time as the license is transferred to the licensee and the licensee is able to use, and benefit from the license.
The restriction will be based on the estimated 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 recovered.
We currently expect revenue from United Kingdom customers to only represent a small proportion of our overall activity. If the proportion of revenue from United Kingdom customers increases this would further restrict the amount of United Kingdom input VAT recovered.
The benefits from U.K. research and development tax credits are recognized in the statements of operations and comprehensive loss as a reduction of research and development expenses and represents the sum of the research and development tax credits recoverable in the U.K. 106 Table of contents 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.
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 decreased to 18.6% after April 1, 2023.
The U.K. Government also enacted further changes to the SME regime effective from April 1, 2023 (with some amendments effective for accounting periods commencing after April 1, 2024) which included the introduction of a new rate for R&D intensive companies of 27%.
The United Kingdom government enacted changes to the SME regime effective from April 1, 2023 which included the introduction of a new rate for R&D intensive companies of 27%.
Cost of Sales Cost of sales amounting to $11.4 million was recognized from November 8, 2024, the date of the FDA approval of AUCATZYL, to December 31, 2024, consisting primarily of salaries and other employment related costs, including share-based compensation expense, for employees engaged in manufacturing activities related to AUCATZYL, as well as outsourced professional services.
Cost of Sales Cost of sales increased by $85.0 million to $96.4 million for the year ended December 31, 2025 from $11.4 million for the year ended December 31, 2024 relating to increase in salaries and other employment related costs, including share-based compensation expense, for employees engaged in manufacturing activities related to AUCATZYL, as well as outsourced professional services.
We do not allocate employee costs or facility expenses, including depreciation or other indirect costs, to specific programs because these costs are deployed across multiple programs and, as such, are not separately classified.
We do not allocate employee costs or facility expenses, including depreciation or other indirect costs, to specific programs because these costs are deployed across multiple programs and, as such, are not separately classified. We use internal resources primarily to oversee research and development as well as for managing our preclinical development, process development, manufacturing and clinical development activities.
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.
Under the RDEC program, the headline rate for qualifying R&D expenditure is 20% and can generate cash rebates of up to 15% on qualifying R&D expenditure.
Selling, General and Administrative Expenses Selling, general and administrative expenses consist primarily of salaries, related benefits, travel and share-based compensation expense for personnel in executive, finance, legal and other administrative functions. Selling, general and administrative expenses also include allocated facility-related costs, patent filing and prosecution costs and professional fees for marketing, insurance, legal, consulting, accounting and audit services.
Selling, General and Administrative Expenses Selling, general and administrative expenses consist primarily of salaries, related benefits, travel and share-based compensation expense for personnel in executive, finance, legal and other administrative functions.
The increase in interest income of $18.9 million primarily relates to higher account balances associated with our cash, cash equivalents and marketable securities during the year ended December 31, 2024 as compared to the year ended December 31, 2023.
The decrease in interest income of $13.4 million primarily relates to lower aggregate balances and yield associated with our cash, cash equivalents and available-for-sale securities during the year ended December 31, 2025 as compared to the year ended December 31, 2024.
Net cash used in operating activities resulting from changes in our operating assets and liabilities for the year ended December 31, 2023 consisted primarily of a decrease in a $13.6 million in operating lease liabilities and a decrease in accounts payable of $0.5 million, offset by a $12.4 million decrease in prepaid expenses and other current and non-current assets, a decrease in long-term deposits of $0.9 million and an increase in accrued expenses and other liabilities of $1.0 million.
Net cash used in operating activities resulting from changes in our operating assets and liabilities for the year ended December 31, 2025 consisted primarily of an increase in inventories of $40.2 million, an increase in accounts receivable of $24.1 million and an increase in increase in prepaid expenses and other current and non-current assets of $4.6 million, offset by an increase of $14.6 million in operating lease liabilities, an increase in accounts payable of $1.3 million, and an increase in accrued expenses and other liabilities of $1.0 million, During the year ended December 31, 2024, operating activities used $206.3 million of cash, resulting from our net loss of $220.7 million, and net cash used resulting from changes in our operating assets and liabilities of $23.6 million, partially offset by non-cash charges of $38.0 million.
If there are changes to the estimates, we recognize the impact to the liability’s amortization schedule and the related interest expense using the catch-up method. Our estimate of the probability, timing and amount of expected future royalties and milestones to be paid by us and the expected Blackstone Development Payment to be paid to us, considers significant unobservable inputs.
Each reporting period we assess the estimated probability, timing and amount of the future expected royalty, milestone payments, the Blackstone Development Payment over the estimated term. If there are changes to the estimates, we recognize the impact to the liability’s amortization schedule and the related interest expense using the catch-up method.
Selling, General and Administrative Expenses Selling, general and administrative expenses increased by $54.3 million to $101.0 million for the year ended December 31, 2024 from $46.7 million for the year ended December 31, 2023 primarily due to: • an increase of $29.1 million in salaries and other employment related costs including share-based compensation expenses, which was mainly driven by an increase in the number of employees engaged in general and administrative activities; • an increase of $22.1 million in commercial readiness costs including legal and professional fees due to increased commercial readiness activities being undertaken; and • an increase of $3.1 million in information technology infrastructure and support for information systems and facility costs relating related to the conduct of corporate and commercial operations and the increase in space utilized for general and administrative activities and related to general office expenses.
Selling, General and Administrative Expenses Selling, general and administrative expenses increased by $30.2 million to $131.9 million for the year ended December 31, 2025 from $101.7 million for the year ended December 31, 2024 primarily due to: • an increase of $20.4 million in salaries, other employment related costs and termination benefits including share-based compensation expenses, which was mainly driven by an increase in the number of employees engaged in general and administrative activities; • an increase of $6.9 million in information technology infrastructure and support for information systems, facility costs, depreciation and impairment on right of use assets and related property and equipment relating to the conduct of corporate and commercial operations including increase in space utilized for these activities; and • an increase of $2.9 million in commercial costs, including legal and professional fees due to increased activity in support of U.S. and international market access;. 114 Table of contents Foreign Exchange Gains (Losses), Net Foreign exchange gains (losses), net increased to a gain of $2.2 million for the year ended December 31, 2025 from a loss of $1.0 million for the year ended December 31, 2024.
Other Income, net Other income (expense), net consists primarily of sublease income and gains or losses arising from the termination of leases. 107 Table of contents Foreign exchange (losses) gains, net Foreign exchange (losses) gains, net consist of foreign currency transaction gains and losses arising from transactions denominated in foreign currencies.
Foreign Exchange Gains (Losses), Net Foreign exchange gains (losses), net consist of foreign currency transaction gains and losses arising from transactions denominated in foreign currencies.
Cost of sales may also include costs related to excess or obsolete inventory adjustment charges and amortization expense of intangible assets.
Cost of sales may also include costs related to excess or obsolete inventory adjustment charges and amortization expense of intangible assets Cost of sales for a newly launched product does not include the full cost of manufacturing until the initial pre-launch raw materials inventory is depleted.
Royalty Revenue For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and the license is deemed to be the predominant item to which the royalties relate, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied).
Royalty Revenue For arrangements that include sales-based royalties, including milestone payments based on the level of sales, and the license is deemed to be the predominant item to which the royalties relate, we recognize revenue at the later of (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the royalty has been allocated has been satisfied (or partially satisfied). 109 Table of contents Cost of Sales Cost of sales represents production costs including raw materials, employee-related expenses, including salaries, related benefits, travel and share-based compensation expense for employees engaged in commercial manufacturing functions, external manufacturing costs including outsourced professional expenses services, allocated facilities costs, depreciation and other expenses, royalties payable to third-parties and other costs incurred in bringing inventories to their location and condition prior to sale.
The total number of ADSs that may be issued to BioNTech is subject to additional limitations and restrictions. BioNTech also has the right to purchase equity securities sold by us in bona fide financing transactions in amounts that are based on BioNTech maintaining specified ownership thresholds following such financing transactions.
We agreed to register those shares as described in the Registration Rights Agreement. Pursuant to the Letter Agreement, BioNTech also has the right to appoint a non-executive director of the Company and to purchase equity securities sold by us in bona fide financing transactions in amounts that are based on BioNTech maintaining specified ownership thresholds following such financing transactions.
Income Tax (Expense) Benefit We are subject to corporate taxation in the U.K., U.S., Germany and Switzerland. Due to the nature of our business, we have generated losses since inception. Our income tax (expense) benefit recognized represents the sum of income tax payable or receivable in the U.K. and in the U.S.
Adjustments to increase or decrease the carrying amount are recognized as an adjustment to interest expense, net in the period in which the change in estimate occurred. Income Tax Expense We are subject to corporate taxation in the United Kingdom, United States, Germany and Switzerland. Due to the nature of our business, we have generated losses since inception.
After accounting for tax credits receivable, we had accumulated tax losses for carry forward in the U.K. of $545.6 million at December 31, 2024 and $418.1 million at December 31, 2023.
The amount that can be offset each year is limited to £5.0 million plus an incremental 50% of United Kingdom taxable profits. After accounting for tax credits receivable, we had accumulated tax losses for carry forward in the U.K. of $953.6 million at December 31, 2025 and $545.6 million at December 31, 2024.
Strategic Financing Agreements BioNTech On February 6, 2024, we, through our wholly owned subsidiaries, Autolus Limited and Autolus Holdings (UK) Limited entered into a License and Option Agreement (the “License Agreement”) with BioNTech SE (“BioNTech”) pursuant to which we granted to BioNTech an exclusive, worldwide, sublicensable license (the “License”) to certain binders and to exploit products that express in vivo such binders (collectively, the “Binder Licensed Products”).
Early stage pipeline programs and collaborations: • Autolus’ translational programs with UCL continue to fuel its early-stage pipeline, providing a cost-efficient path to development to support long-term growth • In November 2025, Moderna announced that the first patient has been dosed in a Phase 1/2 study of mRNA-2808, an investigational mRNA-based T-cell engager for participants with relapsed or refractory multiple myeloma. mRNA-2808 utilizes Autolus’ proprietary binder that was licensed to Moderna in 2022. 105 Table of contents Strategic Financing Agreements BioNTech On February 6, 2024, we, through our wholly owned subsidiaries, Autolus Limited and Autolus Holdings (UK) Limited entered into a License and Option Agreement (the “License Agreement”) with BioNTech SE (“BioNTech”) pursuant to which we granted to BioNTech an exclusive, worldwide, sublicensable license (the “License”) to certain binders and to exploit products that express in vivo such binders (collectively, the “Binder Licensed Products”).
These translations should not be considered representations that any such amounts have been, could have been or could be converted into U.S. dollars at that or any other exchange rate as of that or any other date. Overview We are an early commercial-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer and autoimmune diseases.
These translations should not be considered representations that any such amounts have been, could have been or could be converted into U.S. dollars at that or any other exchange rate as of that or any other date. Autolus, AUCATZYL and our other trademarks or service marks appearing in this report are our property.
Variable consideration is not constrained if the potential reversal of cumulative revenue recognized is not significant, for example. 104 Table of contents If the consideration in a contract includes a variable amount, we will estimate the amount of consideration in exchange for transfer of promised goods or services.
If the consideration in a contract includes a variable amount, we will estimate the amount of consideration in exchange for transfer of promised goods or services. The consideration also can vary if our entitlement to the consideration is contingent on the occurrence or non-occurrence of a future event.
Un-surrendered U.K. losses may be carried forward indefinitely to be offset against future taxable profits, subject to numerous utilization criteria and restrictions. The amount that can be offset each year is limited to £5.0 million plus an incremental 50% of United Kingdom taxable profits.
Our income tax (expense) benefit recognized represents the sum of income tax payable or receivable in the United Kingdom and in the United States. 112 Table of contents Un-surrendered U.K. losses may be carried forward indefinitely to be offset against future taxable profits, subject to numerous utilization criteria and restrictions.
R&D tax credits (decrease in R&D expense) due primarily to an increase in qualifying research and development expenditures related to the SME scheme.
R&D tax credits (increase in R&D expense) due primarily to a decrease in qualifying research and development expenditures; • an increase of $4.4 million in research and development activities including, clinical manufacturing costs, clinical CRO costs and other related activities; and • an increase of $1.3 million in legal fees and professional consulting fees in relation to our research and development activities.
Management does not know whether additional financing will be on terms favorable or acceptable to us when needed, if at all. If adequate additional funds are not available when required, or if we are unsuccessful in entering into partnership agreements for further development of our product candidates, management may need to curtail its development efforts and planned operations.
Management does not know whether additional financing will be on terms favorable or acceptable to us when needed, if at all.
During the year ended December 31, 2023, net cash used in financing activities was $0.9 million which pertains primarily to payments of equity issuance costs relating to a prior equity financing transaction..
Net Cash (Used In) Provided By Financing Activities During the year ended December 31, 2025, net cash used in financing activities was $4.3 million related to revenue share payments.
In the event we generate profits in the future, we may benefit from the U.K.
In the event we generate profits in the future, we may benefit from the U.K. “patent box” regime that allows profits attributable to revenues from patents or patented products to be taxed at an effective rate of 10%.
As a company that carries out extensive research and development activities, we benefit from the SME regime and, to the extent that our projects are grant funded, the RDEC regime .
As a company that carries out extensive research and development activities, we benefit from the Research and Development tax incentives provided by United Kingdom tax legislation. The specific provisions available to claim under vary year on year dependent on the criteria met.
License revenue of $1.7 million for the year ended December 31, 2023 primarily related to the execution of the Cabaletta Bio Inc. (“Cabaletta”) Option and License Agreement, which included recognition of a non-refundable license fee and license revenue from an investee of Syncona Portfolio Limited, which is a holder of more than 10% of our share capital.
License revenue of $10.1 million for the year ended December 31, 2024 primarily related to license revenue recognized pursuant to the License and Option Agreement with BioNTech.
In addition, based on the relevant tax legislation, we may meet the conditions of the R&D intensive scheme. From January 2025, we will not qualify as a small or medium-sized enterprise under the SME program, based on size criteria concerning employee headcount, turnover and gross assets.
These changes apply to periods commencing after April 1, 2024. 111 Table of contents In the accounting period ended December 31, 2025, we will not qualify for relief under the SME program, based on size criteria concerning employee headcount, turnover and gross assets. However, we may make a claim under the merged RDEC regime, as detailed above.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeCredit Risk We are exposed to credit risk from our operating activities, primarily from available for sale debt securities and cash and cash equivalents. Our cash and cash equivalents and available for sale debt securities are held with multiple counterparties for varying periods according to our expected liquidity requirements.
Biggest changeCredit Risk We are exposed to credit risk from our operating activities, primarily from cash and cash equivalents and available for sale debt securities. Our cash and cash equivalents and available for sale debt securities are held with multiple counterparties for varying periods according to our expected liquidity requirements.
Our investment policy limits investments to certain types of instruments, such as available for sale debt securities, money market funds, bank term deposits and bank notice accounts and places restrictions on maturities and concentration by type and issuer and specifies the minimum credit ratings for all investments and the average credit quality of the portfolio.
Our investment policy limits investments to certain types of instruments, such as available for sale debt securities, money market funds, bank term deposits and bank notice accounts and places restrictions on maturities and concentration by type and issuer and specifies the minimum credit ratings for all investments and the average credit quality of the portfolio. Item 8.
As of December 31, 2024 and 2023, the Blackstone Collaboration Agreement Liability has a fixed effective interest rate and is not subject to any fluctuations due to interest rates. However, the effective interest rate for the BioNTech Liability may be subject to fluctuations due to the discretionary nature of certain contractual payments to us.
As of December 31, 2025 and 2024, the Blackstone Collaboration Agreement Liability has a fixed effective interest rate and is not subject to any fluctuations due to interest rates. However, the effective interest rate for the BioNTech Liability may be subject to fluctuations due to the discretionary nature of certain contractual payments to us.
We maintain significant amounts of cash that are in excess of federally insured limits in various currencies, placed with one or more financial institutions for varying periods according to expected liquidity requirements. 115 Table of contents Interest Rate Risk Our exposure to interest rate sensitivity is primarily impacted by changes in the underlying U.S. and U.K. bank interest rates.
We maintain significant amounts of cash that are in excess of federally insured limits in various currencies, placed with one or more financial institutions for varying periods according to expected liquidity requirements. Interest Rate Risk Our exposure to interest rate sensitivity is primarily impacted by changes in the underlying U.S. and U.K. bank interest rates.
Exchange gains or losses arising from foreign currency transactions are included in the determination of net income (loss) for the respective periods. We recorded a foreign exchange loss of $1.0 million and a foreign exchange gain $2.6 million for the years ended December 31, 2024 and 2023 respectively in the consolidated statements of operations and comprehensive loss.
Exchange gains or losses arising from foreign currency transactions are included in the determination of net income (loss) for the respective periods. We recorded a foreign exchange gain of $2.2 million and a foreign exchange loss of $1.0 million for the years ended December 31, 2025 and 2024 respectively in the consolidated statements of operations and comprehensive loss.
The significant remainder of our cash and cash equivalents are held by our U.S. subsidiary and denominated in U.S. dollars. We maintain our accounting records in pounds sterling, our functional currency, and present our consolidated financial statements in U.S. dollars for financial reporting purposes.
The significant remainder of our cash and cash equivalents are held by our U.S. subsidiary and denominated in U.S. dollars. 120 Table of contents We maintain our accounting records in pounds sterling, our functional currency, and present our consolidated financial statements in U.S. dollars for financial reporting purposes.
An immediate hypothetical one percentage point change in interest rates would have resulted in a $2.3 million increase in interest income on our consolidated statements of operations and comprehensive loss for the year ended December 31, 2024.
An immediate hypothetical one percentage point change in interest rates would have resulted in a $1.0 million increase in interest income on our consolidated statements of operations and comprehensive loss for the year ended December 31, 2025.
As of December 31, 2024 and 2023, we had cash and cash equivalents of $227.4 million and $239.6 million, respectively. Our surplus cash has been invested in interest-bearing savings, money market funds and available for sale debt securities.
As of December 31, 2025 and 2024, we had cash and cash equivalents of $104.1 million and $227.4 million, respectively. Our surplus cash has been invested in interest-bearing savings, money market funds and available for sale debt securities.
As of December 31, 2024, substantially all of our cash and cash equivalents were held by one of our U.K. subsidiaries, of which approximately 62% were denominated in pound sterling and approximately 38% were denominated in U.S. dollars, with immaterial amounts denominated in euros and Swiss francs.
As of December 31, 2025, substantially all of our cash and cash equivalents were held by one of our U.K. subsidiaries, of which approximately 36% were denominated in pound sterling and approximately 60% were denominated in U.S. dollars, with immaterial amounts denominated in euros and Swiss francs.
Added
Financial Statements and Supplementary Data The consolidated financial statements required to be filed pursuant to this Item 8 begin on page F-1 of this Annual Report. Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure None.

Other AUTL 10-K year-over-year comparisons