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Item 1. Business

2026-03-27 compared with 2025-03-20 · 388 added, 352 removed, 962 unchanged (43% of the section changed)

Business Overview

We are an early commercial-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer and autoimmune diseases.

On November 8, 2024, the U.S.

Food and Drug Administration, or FDA, granted marketing approval for our first approved commercial product, AUCATZYL/obe-cel (obecabtagene autoleucel) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, or r/r B-ALL.

We commercially launched AUCATZYL in the United States in January 2025, and we plan to initiate sales of AUCATZYL/obe-cel in the European Union, or EU, and the United Kingdom, or UK, once regulatory approval is received.

Marketing authorization submissions for AUCATZYL/obe-cel were accepted by the European Medicines Agency, or EMA, in April 2024 and the U.K.

Medicines and Healthcare products Regulatory Agency, or MHRA, in August 2024, and we expect to receive notification of approval status from these authorities in the second half of 2025.

AUCATZYL is a CD19-targeting programmed T cell investigational therapy with a CD19 binder designed to improve the efficacy and safety profile, as compared to other CD19 CAR T chimeric antigen receptor T cell, or CAR T, therapies.

Adult r/r/ B- ALL is an extremely aggressive type of blood cancer with a high unmet medical need in the treatment of patients once they relapse, where historically patients suffer from poor outcomes.

AUCATZYL is manufactured at our dedicated commercial manufacturing site, the Nucleus, in Stevenage, UK.

If we receive approval to commercialize AUCATZYL outside of the United States, we intend for the Nucleus to meet the global supply demands of AUCATZYL, with Cardinal Health serving as our commercial distribution partner in the United States.

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 is also being developed for the treatment of autoimmune indications and we have initiated a Phase 1 study in patients with severe, refractory systemic lupus erythematosus (“SLE”).

Using our broad suite of proprietary and modular T cell programming technologies, we are also developing five programs in seven hematological and solid tumor indications and one autoimmune indication.

We are engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize target cells, break down their defense mechanisms and attack and eliminate these cells.

We are an early commercial-stage biopharmaceutical company developing, manufacturing and delivering next-generation T cell therapies and candidates for the treatment of cancer and autoimmune diseases.

Using our broad suite of proprietary and modular T cell programming technologies, we are engineering precisely targeted and controlled T cell therapies that are designed to better recognize target cells, break down their defense mechanisms and eliminate target cells.

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.

In November 2024, the United States Food and Drug Administration (the “FDA”) approved our biologics license application (“BLA”) for the marketing of AUCATZYL (obecabtagene autoleucel, also known as obe-cel) in the United States for the treatment of adult patients (18 years and older) with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (“r/r B-ALL”).

The commercial launch and first sale of AUCATZYL in the United States occurred in January 2025.

The United Kingdom Medicines and Healthcare products Regulatory Agency (“MHRA”) granted AUCATZYL conditional marketing authorization in April 2025.

In November 2025, the National Institute for Health and Care Excellence (“NICE”) recommended AUCATZYL for use in the National Health Service (“NHS”) in England and Wales as a treatment option for adult patients (age 26 and older) with r/r B-ALL.

We launched AUCATZYL in the United Kingdom in January 2026, and it is available through routine commissioning by the NHS.

In July 2025, the European Commission (“EC”) granted marketing authorization for AUCATZYL in adult patients (age 26 and older) with r/r B-ALL.

Evaluation of potential pricing and feasibility of market entry opportunities in certain European Union (“EU”) countries is ongoing;

however, at this time, launch in the EU is on hold and we do not anticipate any EU sales of AUCATZYL in 2026.

AUCATZYL is a B-lymphocyte antigen CD19 (“CD19”) chimeric antigen receptor (“CAR”) T cell therapy.

AUCATZYL is designed with a fast target binding off-rate to minimize excessive activation of the programmed T cells.

Adult r/r B- ALL is an extremely aggressive type of blood cancer with a high unmet medical need in the treatment of patients once they relapse, where historically patients suffer from poor outcomes.

AUCATZYL is manufactured at our dedicated commercial manufacturing site, the Nucleus, in Stevenage, U.K.

We intend for the Nucleus to meet the global supply demands of AUCATZYL, with Cardinal Health 105, LLC serving as our commercial distribution partner in the US.

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.

Data from the Phase 1b cohort of the ongoing Phase 1b/2 CATULUS trial evaluating the safety and efficacy of obe-cel in pediatric B-ALL and B-NHL patients was presented at the American Society of Hematology (“ASH”) Annual Meeting in December 2025.

Data show the safety profile of obe-cel in pediatric patients is consistent with that previously reported in adults, with low rates of high-grade cytokine release syndrome (“CRS”) and immune effector cell-associated neurotoxicity syndrome (“ICANS”).

Overall response rate (“ORR”) was high at 95%, and nearly 90% of responders had ongoing remission at data cut-off.

Enrollment into the Phase 2 cohort is ongoing, and in October 2025, the FDA granted regenerative medicine advanced therapy (“RMAT”) designation to obe-cel for the treatment of pediatric patients with r/r B-ALL.

We expect to have Phase 2 cohort of the trial fully enrolled in the first half of 2027.

Obe-cel is also being developed for the treatment of autoimmune indications, and we have initiated a Phase 1 trial in patients with severe, refractory systemic lupus erythematosus (“SLE”).

Data from the ongoing Phase 1 CARLYSLE trial evaluating obe-cel in patients with severe refractory systemic lupus erythematosus was presented at the ASH Annual Meeting in December 2025.

The data showed deep, durable responses in patients receiving the 50 million obe-cel CAR t-cell dose level, and initial data suggest substantial early improvement in three patients dosed with obe-cel at 100 million dose level.

All patients show deep B-cell depletion after infusion, suggesting an immune reset.

Nine patients were evaluable for safety, and no ICANS or high-grade CRS were observed.

The Company has advanced obe-cel into a Phase 2 potentially pivotal study known as LUMINA in patients with severe, refractory lupus nephritis (“LN”).

We are advancing obe-cel into clinical development in progressive multiple sclerosis (“MS”) and in October 2025, we have dosed our first patients in a Phase 1 dose escalation clinical trial, with initial data expected to be reported at the end of 2026.

Our T cell programming technologies allow us to tailor our therapies to address the specific disease we are targeting and introduce new programming modules into a patient’s T cells to give those T cells improved properties to better recognize target cells and overcome fundamental disease defense mechanisms.

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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.

Our current clinical-stage pipeline comprises five programs being developed in seven hematological and solid tumor indications and one autoimmune indication.

Our current clinical-stage pipeline comprises four programs being developed in eight hematological and solid tumor indications and two autoimmune indications.

Our current pipeline is below:

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The particular modules selected may vary, and not every product candidate, including our current product candidates, contain all categories of modules.

A viral vector is used to introduce combinations of these modules into the DNA of the T cells, as depicted in the graphic below.

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.

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Our strategic priorities include:

• Execute on the U.S.

launch and commercialization of AUCATZYL/obe-cel for adult r/r B-ALL

• Subject to receiving regulatory approval, launch AUCATZYL/obe-cel for adult r/r B-ALL in the U.K.

and European Union

• Develop obe-cel for treatment of potential additional indications, including Lupus

• Build our research and development pipeline

Background on T Cells and Cancer

• Continue building upon United States and United Kingdom commercialization of AUCATZYL for adult r/r B-ALL.

• Optimize our manufacturing operations to improve gross margin, and innovate on a next-generation manufacturing platform.

• Evaluate the potential pricing and feasibility of market entry opportunities in certain EU countries.

• Develop obe-cel for treatment of potential additional indications, including pediatric r/r B-ALL, LN and MS.

Programmed T Cell Therapies

Chimeric Antigen Receptors ( “ CARs ” )

We use CARs to reprogram our T cell product candidates.

These receptors combine the antigen recognition domain of an antibody with the activation and costimulatory domains from the T cell receptor to rearm a patient’s T cells to recognize and kill target cells.

CAR T Cell Production

We have developed our own proprietary viral vector and semi-automated cell manufacturing processes to engineer a patient's T cells with the CAR and other programming modules.

We believe that this autologous approach has the potential to be both the safest and most therapeutically effective approach to manufacturing CAR T cells.

Our technological approach is the development of advanced T cell engineering components designed to directly address clinical challenges.

A focus in our early-stage pipeline is incorporation of multiple components in a single product.

Programmed T Cell Therapies for the Treatment Cancers

Cancers originate from individual cells that have developed mutations in essential cellular programs, driving increased cell division and growth.

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For a cancer to grow to the detriment of the patient, cancer cells evolve mechanisms to evade recognition by, or establish other defenses against, T cells.

Cancer Immunotherapy and T cell Therapies

In recent years we have seen the emergence of cancer immunotherapy, in which treatments harness the power of a patient’s immune system to combat their disease.

Cancer immunotherapy treatment requires the activation and expansion of cancer-specific T cells, which kill cancer cells by recognizing antigen targets expressed on cancer cells.

Studies have shown that tumors develop escape mechanisms that prevent T cell-mediated destruction through immune checkpoint proteins, which shut down anti-tumor immunity.

Studies have shown that tumors develop escape mechanisms that prevent T cell-mediated destruction through immune checkpoint proteins, which shut down antitumor immunity.

Clinical trials have shown that treatment with immune checkpoint inhibitors can restore T cell activity and results in durable clinical responses.

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We believe our commercial product and our clinical-stage product candidates and our approach to T cell programming have the potential to address these limitations.

Programmed T Cell Therapies

Chimeric Antigen Receptors ( “ CARs ” )

We use CARs to reprogram our T cell product candidates.

These receptors combine the tumor recognition domain of an antibody with the activation and costimulatory domains from the T cell receptor to rearm a patient’s T cells to recognize and kill their cancer cells.

CAR T Cell Production

We have developed our own proprietary viral vector and semi-automated cell manufacturing processes to engineer a patient's T cells with the CAR and other programming modules.

We believe that this autologous approach has the potential to be both the safest and most therapeutically effective approach to manufacturing CAR T cells.

Limitations of Current T Cell Immunotherapies

Existing T cell immunotherapies, including CAR T therapies, have shown significant efficacy in hematological malignancies;

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Advanced Targeting Technologies

We have developed advanced antigen targeting technologies to improve the ability of our programmed T cell therapies to selectively identify and target cancer cells and to deliver a sustained anti-tumor effect.

These targeting technologies include fast off-rate CARs, novel targets, high avidity spacers, dual-targeting and pattern recognition.

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We have designed programmed T cells with fast off-rate binders.

These fast off-rate kinetics are similar to the behavior of naturally occurring T cells.

These fast off-rate kinetics are similar to the behaviour of naturally occurring T cells.

Obe-cel has this enhanced kinetic profile, which, when compared to data reported for other CAR T cell product candidates in clinical development for ALL that use high affinity binders, appears to result in reduced Cytokine Release Syndrome and in increased T cell engraftment.

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We have developed multiple technologies designed to pharmacologically control T cell activity in the event a patient suffers certain serious adverse events related to the T cell therapy.

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.

Rituximab Safety Switch (RQR8)

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TetCAR is a controllable CAR T cell system designed to reversibly dampen the activity of the programmed T cells by the administration of the commercially available antibiotic tetracycline to a patient.

Once administered, tetracycline temporarily dislocates the CAR signaling domain from the cancer antigen binding domain leading to deactivation of the T cell therapy.

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 anti-tumor immune responses.

Tumor cells and other cells in the tumor microenvironment can debilitate antitumor immune responses.

Proteins expressed on tumor cells can trigger inhibitory receptors on T cells to block their ability to eliminate the tumor.

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Checkpoint Shielding (dSHP2)

Immune checkpoint receptors act through a common signaling pathway inside the T cell that prevents normal T cell activation.

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.

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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.

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.

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.

Certain cytokines can potentiate the antitumor of the T cell therapy by recruiting and activating other immune cells to kill the tumor.

However, systemic or local administration of cytokines can be toxic, therefore we have developed programming modules that are designed to harness the enhanced activity of cytokines whilst avoiding the potential for toxicities.

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The CCR is a programming module that is designed to deliver a cytokine signal directly inside T cells without administration or secretion of cytokines themselves.

We use proteins from an antibody structure to stably heterodimerize two cytokine signaling domains together to deliver a proliferative and survival signal into our T cells.

We use proteins from an antibody structure to stably heterodimerize two cytokine signalling domains together to deliver a proliferative and survival signal into our T cells.

Preclinical data has demonstrated the potential for the CCR to improve the persistence and activity of CAR T cell therapy against solid tumors.

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Host Immune System Recruitment (ssIL12)

IL-12 is a potent anti-tumor cytokine that mediates the activity of many different anti-tumor immune cells.

IL-12 is a potent antitumor cytokine that mediates the activity of many different antitumor immune cells.

The majority of clinical studies involving treatment of patients with IL-12 were associated with severe systemic side effects mediated by high levels of IFNγ.

Our ssIL12 module is designed to secrete very low levels of IL-12 from our T cells and our preclinical data demonstrates the potential for ssIL12 to provide anti-tumor without systemic toxicity.

Our ssIL12 module is designed to secrete very low levels of IL-12 from our T cells and our preclinical data demonstrates the potential for ssIL12 to provide antitumor activity without systemic toxicity.

Engineering survival signal (Fas-TNFR)

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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.

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.

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Rapid disengagement from the target antigen is expected to minimize excessive activation of the programmed T cells, reduce toxicity and may also reduce T cell exhaustion.

The US FDA granted marketing approval for obe-cel for the treatment of adult patients with r/r B-ALL on November 8, 2024 under the brand name AUCATZYL.

Marketing authorization applications (“MAA”) for AUCATZYL/obe-cel in adult r/r ALL are being reviewed by the regulators in both EU and the U.K., with a submission to the EMA accepted in March 2024, and a submission accepted by the U.K.

MHRA in August 2024.

We expect to receive notification of approval status from these authorities in the second half of 2025.

Clinical Development of Obe-cel in Adult ALL

Background of Adult ALL

Obe-cel was tested in a Phase 1b/2 clinical trial for the treatment of adult ALL, which according to the American Cancer Society is predicted to affect approximately 6,500 adults in the United States in 2023.

According to the American Cancer Society, adult ALL was predicted to affect approximately 6,500 adults in the United States in 2023.

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 to three decades, with long-term remission rates limited to 30-40%.

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%.

Approximately 50% of all adult ALL patients will relapse, and data from the Medical Research Council’s UKALL12/ECOG 2993 study, published in 2007, found that five-year overall survival (“OS”), rate in adults who relapse following standard multi-agent chemotherapy is 7%.

In a published 2016 retrospective analysis conducted by the Group for Research on Adult Acute Lymphoblastic Leukemia on adult patients (age 18-63) in France, Belgium and Switzerland relapsing after first-line pediatric-inspired therapy, the overall survival at 2 and 5 years was 19.3% (14–24%) and 13.3% (8–18%), respectively.

The only curative option for relapsed or refractory ALL consists of achieving a second CR by salvage therapy followed by an allogeneic hematopoietic stem cell transplant (“allo-HSCT”).

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Further, allo-HSCT is associated with severe morbidity and significant mortality.

Many patients with relapsed or refractory ALL will have been maximally treated with chemotherapy, and often do not achieve a second CR with standard-of-care chemotherapy in order to be eligible for allo-HSCT.

Two targeted immunotherapies have been approved in a number of jurisdictions, including the United States and the EU, for the treatment of adult ALL:

Many patients with relapsed or refractory ALL will have been maximally treated with chemotherapy, and often do not achieve a second CR in order to be eligible for allo-HSCT.

Two targeted monoclonal based therapies have been approved in a number of jurisdictions, including the United States and the EU, for the treatment of adult ALL:

blinatumomab and inotuzumab ozogamicin.

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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.

On October 1, 2021 the FDA approved the use of the CAR T cell therapy brexucabtagene autoleucel (“Tecartus”) for adults with B-cell precursor ALL that has not responded to treatment (refractory) or has returned after treatment (relapsed).

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We initiated the FELIX study, a Phase 1b/2 clinical trial of obe-cel for the treatment of adult r/r B-Acute Lymphoblastic Leukemia, in 2020.

Most recently the data were published in the New England Journal of Medicine in December 2024.

The data were published in the New England Journal of Medicine in December 2024.

The published data were from a pooled analysis of data from all patients across all cohorts in the FELIX Phase 1b/2 study.

Of the 153 r/r B-ALL patients enrolled patients in the FELIX study, 127 (83.0%) received at least one obe-cel infusion and were evaluable.

Of the 153 r/r B-ALL patients enrolled in the FELIX study, 127 (83.0%) received at least one obe-cel infusion and were evaluable.

Eligible patients underwent leukapheresis, and bridging therapy, except blinatumomab, was permitted at the investigator’s discretion.

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In 6/18 (33.3%), this was a second allo-SCT.

Of 11 patients who had persisting CAR T cells before allo-SCT, and who had samples available post, none had CAR T cells detected following allo-SCT.

There was no difference in event-free and overall survival observed between patients who received allo-SCT and those who did not.

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.

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.

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).

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).

Most recently at the European Hematology Association annual meeting in 2025, longer term follow up data from the FELIX study were presented.

At the updated median follow up of 32.8 months, 38.4% of responders were in ongoing remission without consolidative allo-SCT or other therapies.

The 24-month probability of Event Free Survival was 43%, and for Overall Survival was 46%, with an emerging long-term plateau observed.

A substantial subset of patients benefit from standalone treatment with obe-cel, achieving long-term remission.

No new safety signals or Grade ≥3 secondary malignancies were observed at the extended follow-up.

These results suggest that obe-cel may be a definitive treatment for some patients with r/r B-ALL.

Obe-cel Phase 1 Clinical Trial in Adult ALL (ALLCAR19 Trial)

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Regulatory Status and Plans

Obe-cel has received a number of designations from regulatory authorities, as follows:

FDA orphan drug designation for the treatment of ALL (October 2019), EMA PRIME designation (March 2021), MHRA ILAP designation (June 2021), European Commission orphan drug designation (March 2022), and FDA RMAT designation (April 2022).

The US FDA granted marketing approval for obe-cel on November 8, 2024 under the brand name AUCATZYL for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r B-ALL) without the need for a Risk Evaluation and Mitigation Strategy (REMS).

The US FDA granted marketing approval for obe-cel on November 8, 2024 under the brand name AUCATZYL for the treatment of r/r B-ALL.

The approval is based on data from the Phase 2 cohort of FELIX study.

MAAs for obe-cel in r/r B-ALL are being reviewed by the regulators in both the EU and the UK, with a submission to the EMA accepted in March 2024, and a submission accepted by the U.K.

MHRA in August 2024.

Based on prior regulatory timelines, we expect to hear from the MHRA and EMA regarding potential marketing approvals in the second half of 2025.

The MHRA granted AUCATZYL conditional marketing authorization in April 2025 for Adult Patients (≥ 18 years) with r/r B-ALL.

In November 2025, NICE recommended AUCATZYL for use in the National Health Service (“NHS”) in England and Wales as a treatment option for adult patients (≥26 years) with r/r B-ALL.

We launched AUCATZYL in the United Kingdom in January 2026, and it is available through routine commissioning by the NHS.

On 17 July 2025, the European Commission (“EC”) granted marketing authorization for AUCATZYL in adult patients (age 26 and older) with r/r B-ALL.

Evaluation of potential pricing and feasibility of market entry opportunities in certain European Union (“EU”) countries is ongoing;

however, at this time, launch in the EU is on hold and the Company does not anticipate any EU sales of AUCATZYL in 2026.

Commercialization Strategy for AUCATZYL

FDA has granted marketing approval for AUCATZYL for the treatment of patients with r/r B-ALL.

We are now in the process of launching the product in the US.

This required several bespoke elements, including the processes for distribution, patient scheduling, center engagement and service hub to be established.

It is a requirement that the product is administered only by authorized centers that are specialized in hematology and have the necessary infrastructure and capabilities for administering CAR-T therapies.

We achieved our target 33 centers fully authorized to deliver AUCATZYL by end of January 2025, covering 60% of the accessible patient population, and this number of centers will steadily increase with the expectation it will be over 50 centers by mid-2025.

We expect to complete authorization of 60 treatment centers, covering approximately 90% of the target patient population, by the end of 2025.

In December 2024, the National Comprehensive Cancer Network®, or NCCN, added AUCATZYL to its Clinical Practice Guidelines in Oncology, or NCCN Guidelines®, for the treatment of adult r/r B-ALL.

The NCCN is a not-for-profit alliance of 30 leading cancer centers devoted to patient care, research, and education.

The NCCN Guidelines are a comprehensive set of guidelines detailing the sequential management decisions and interventions that currently apply to 97% of cancers affecting patients in the U.S and are intended to ensure that all patients receive preventive, diagnostic, treatment, and supportive services that reflect the latest evidence in oncological patient care.

We have retained worldwide commercial rights for AUCATZYL.

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 may pursue strategic collaborations with third parties in order to maximize the commercial potential of AUCATZYL.

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 generally expect to launch any of our products that receive regulatory approval in the United States first, followed by the U.K., EU and subsequently in other major markets.

The product option for AUTO1/22 was not exercised and has expired as of February 8, 2025.

Having achieved marketing approval for AUCATZYL for the treatment of patients with r/r B-ALL in the US, U.K and parts of Europe, we are expanding upon our commercial launch in those countries.

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.

The product may be administered only by authorized centers that are specialized in hematology and have the necessary infrastructure and capabilities for administering CAR-T therapies.

In December 2024, AUCATZYL was added to the National Comprehensive Cancer Network®, (“NCCN”) Clinical Practice Guidelines in Oncology, (“NCCN Guidelines®”), for the treatment of adult r/r B-ALL.

The NCCN is a not-for-profit alliance of 30 leading cancer centers devoted to patient care, research, and education.

The NCCN Guidelines are a comprehensive set of guidelines detailing the sequential management decisions and interventions that currently apply to 97% of cancers affecting patients in the US and are intended to ensure that all patients receive preventive, diagnostic, treatment, and supportive services that reflect the latest evidence in oncological patient care.

See “Risk Factors–Risks Related to our Intellectual Property–Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which would be uncertain and could significantly harm our business.”

Our Manufacturing and Logistics Capabilities

We are devoting significant resources to process development and manufacturing in order to optimize the safety and efficacy of AUCATZYL, to ensure high quality and reliable product supply to patients, as well as to reduce our per unit manufacturing costs and time to market for AUCATZYL and any of our programmed T cell product candidates for which we obtain regulatory approval.

We are devoting significant resources to process development and manufacturing in order to ensure high quality and reliable product supply to patients, as well as to reduce our per unit manufacturing costs and time to market for AUCATZYL and any of our programmed T cell product candidates for which we obtain regulatory approval.

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.

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Our manufacturing and logistics process is designed to ensure that product integrity is maintained during shipment along with accurate tracking and tracing of shipments.

We are expanding internal manufacturing and supply capabilities as well as the use of expert service providers on maturing our vein-to-vein logistics and our gradual capacity expansion in support of commercial operations.

Chain of identity and chain of custody electronic systems are now in place to ensure transport and processing reliability and further adding to patient safety.

We are expanding internal manufacturing and supply capabilities as well as the use of expert service providers on maturing our vein-to-vein logistics in support of commercial operations.

Chain of identity and chain of custody electronic systems are in place to ensure transport and processing reliability.

Our manufacturing and commercialization strategy requires a fully integrated vein-to-vein product delivery cycle.

We believe having established manufacturing processes suitable for commercialization early in the development of AUCATZYL will allow us to focus on expanding manufacturing capacity during our early commercial launch needs.

Over time, we expect to establish regional manufacturing hubs to meet projected near-, mid- and long-term commercial product requirements for commercialization.

Our first purpose-built facility, the Nucleus, is located in Stevenage, U.K..

This facility, which has a global reach, can meet our near and mid-term clinical and commercial needs allowing ample time for expanding our manufacturing footprint.

Our plan is to establish our manufacturing infrastructure in a manner that would minimize logistical complexities and costs for all regions going forward.

The licensure and commercial supply of our cell products will be from our 70,000 square foot facility called the Nucleus, in Stevenage, United Kingdom.

We believe this facility, which has a global reach, can meet our near and mid-term clinical and commercial needs allowing ample time for expanding our manufacturing footprint.

In March 2024, following the most recent GMP inspection by the MHRA in February 2024, the Nucleus facility obtained a Manufacturer’s Importation Authorization (MIA) together with the accompanying GMP certificate.

Having established manufacturing processes suitable for commercialization early in the development of AUCATZYL has allowed us to focus on expanding manufacturing capacity during our commercial launch.

Our purpose-built facility, the Nucleus, is located in Stevenage, U.K and covers 70,000 square feet.

This facility, which has a global reach, can meet our near and mid-term clinical and commercial needs allowing ample time for expanding our manufacturing footprint when needed.

In March 2024, the Nucleus facility obtained a Manufacturer’s Importation Authorization (MIA) together with the accompanying Good Manufacturing Practice (“GMP”) certificate.

These licenses enable us to manufacture both commercial and clinical autologous drug products in the facility.

The Nucleus provides multiple clean rooms, QC labs, warehouse and administrative space and is being fitted out in a phased manner as demand requires.

At full capacity, we expect the Nucleus facility to provide manufacturing capacity for approximately 2,000 batches annually, Additional fallow space for the expansion of manufacturing capacity is available if required.

At full capacity, we expect the Nucleus facility to provide manufacturing capacity for approximately 2,500 batches annually.

Our plan is to establish our manufacturing infrastructure in a manner that would minimize logistical complexities and costs for all regions going forward.

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Our Manufacture and Delivery Performance

Data on manufacturing and delivery performance for obe-cel in the FELIX clinical trial were presented at the 2023 ASCO Annual Meeting in June 2023, with updated data presented at the ASH Annual Meeting in December 2023.

Data on manufacturing and delivery performance for obe-cel in the FELIX clinical trial were published in the New England Journal of Medicine in December 2024.

The FELIX study successfully demonstrated the robust operability of obe-cel manufacturing, QC and logistics processes, meeting target V2C (time from leukapheresis to quality release) and V2D (time from leukapheresis to delivery of product to the hospital).

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In total, 96% of manufactured obe-cel batches reached their target dose of 410 x 10 6 CAR T cells.

Further optimization and improvements made during the study increased reliability, consistency, and precision of the manufacturing process, and supported the development of the Nucleus manufacturing facility with greater production capacity that aims to achieve a ≥95% manufacturing success rate with ≤15-day V2C times.

Commercially in 2025 we achieved ≥90% manufacturing success rate.

Manufacturing Agreements with Third Parties

We obtain viral vector for commercial supply of AUCATZYL and for late stage clinical trials from our partner AGC Biologics.

We also have manufacturing agreements with King’s College London for early phase vector manufacturing, and some internal capability to produce vector for early and late-stage trials.

We also have manufacturing agreements with other contract manufacturing and development organizations for early phase vector manufacturing.

All vector manufacturing is done in accordance with current Good Manufacturing Practice (“cGMP”) in compliant manufacturing facilities.

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.

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 supply agreement sets forth procedures to ensure continuity of supply to us of Miltenyi’s products, both during the clinical phase and any future commercial phase of our product candidates.

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.

We amended the supply agreement most recently in September 2023.

The supply agreement sets forth procedures to ensure continuity of supply to us of Miltenyi’s products, both during the clinical phase and commercial phases of our product candidates.

After the initial ten-year term of the agreement, we have two separate options to renew the agreement, each for an additional five-year term.

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The supply agreement is governed under the laws of Germany.

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).

We believe obe-cel has a differentiated safety profile and shows potential for longer term outcomes when compared to these current approved therapies.

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).

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.

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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.

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.

Obe-cel for the Treatment of Pediatric ALL, B-NHL and other B-cell malignancies

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.

The current standard of care for both pediatric and adult B-cell ALL patients is a standard regimen of combination chemotherapy.

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.

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.

In pediatric populations, blinatumomab has demonstrated efficacy both in patients with relapsed or refractory disease, as well as a component of frontline combination therapy for newly diagnosed patients.

The recently published COG AALL1731 trial was a randomized phase 3 trial evaluating the benefit of the addition of blinatumomab to standard chemotherapy in patients with National Cancer Institute (NCI) standard-risk B-ALL.

With a median follow-up of 2.5 years, 3-year DFS was 96.0% ± 1.2% among patients randomized to receive blinatumomab with chemotherapy, compared with 87.9% ± 2.1% in the chemotherapy-alone group (Gupta et al., NEJM 2025).

However, 10 to 20% of pediatric B-cell ALL patients relapse with chemotherapy-resistant disease.

These patients are re-treated with intensive chemotherapy, and those that respond may proceed to receive an allogenic stem cell transplant (“SCT”).

However, SCT can be associated with significant long-term morbidity due to the risk of developing graft-versus-host disease (“GVHD”), and treatment-related mortality, although the risk of death have declined with better post-transplant management.

However, SCT can be associated with significant long-term morbidity due to the risk of treatment associated developmental impairments, developing graft-versus-host disease, and transplant-related mortality, although the risk of death have declined with better post-transplant management.

A phase 3 trial conducted in Europe enrolled children with high risk first relapse of B-ALL (relapse at <18 months after diagnosis or marrow relapse at ≥18 months from diagnosis but <6 months after completion of therapy).

Those achieving an M1 (<5% blasts) or M2 (≥5 but <25% blasts) marrow after reinduction therapy were treated with 2 cycles of standard consolidation chemotherapy and were then randomized to receive either blinatumomab or consolidation chemotherapy before planned allogeneic HSCT.

In total, 108 patients were randomized before early termination of enrollment because of meeting prespecified criteria finding benefit of blinatumomab (Locatelli et al., JAMA 2021;325;(9):843-854.

doi:10.1001/jama.2021.0987).

With a median follow-up of 44 months, blinatumomab demonstrated improved EFS across subgroups and improved OS (HR, 0.34;

95% CI, 0.17-0.69) (Locatelli et al.., Leukemia 37, 222–225 (2023).

https://doi.org/10.1038/s41375-022-01770-3).

In parallel, the COG performed a similar randomized AALL1331 phase 3 study in patients with high-risk (marrow relapse < 36 months after initial diagnosis or isolated EMD relapse <18 months after initial diagnosis) or intermediate risk first relapse.

As in the European trial, randomization was terminated early because of the combination of findings of higher disease-free survival (DFS), OS, and MRD clearance, as well as lower toxicity in the blinatumomab arm compared with the chemotherapy arm (Hall AG and Rau RE, Blood Adv 2025;

https://doi.org/10.1182/bloodadvances.2024014043).

With a median follow-up of 2.9 years, 2-year DFS in the blinatumomab arm was 54.4% vs 39.0% in the chemotherpay arm (HR, 0.7;

95% CI, 0.47-1.03) and OS in the blinatumomab arm was 71.3% vs 58.4% in the chemotherarpy arm (HR, 0.62;

95% CI, 0.39-0.98) (Brown PA et al., JAMA 2021;325;(9):833-842.

doi:10.1001/jama.2021.0669).

Patients with high-risk clinical or genetic features including gene abnormalities, as well as those who have an inadequate response to initial chemotherapy, may not respond well with the current available treatments for B-cell ALL (including SCT), some of these patients will have a five-year OS rate of approximately 15%.

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CD19 CAR T cell therapies have been developed for these patients.

The approved CD19 CAR T therapy, Kymriah, has shown approximately 80% of complete molecular response rate.

The CD19 CAR T therapy, Kymriah, however, is not approved in patients with first relapse.

In the approved indication in refractory patients or patients up to 25 years of age in second or later relapse, Kymriah has shown approximately 80% of complete molecular response rate.

However, at six months after treatment, approximately 40% of the patients relapsed and the majority of the relapses were CD19 negative disease, with approximately two-thirds of relapses determined to have been due to loss of CD19 on the target cells in one study.

CD19 CAR T cell therapies have been tested in pediatric ALL patients and have shown sustained responses without allo-HSCT.

CD19 CAR T cell therapies have been tested in pediatric B-ALL patients and have shown sustained responses without allo-HSCT.

In adult ALL, however, one of the major challenges has been severe toxicity, including death due to CAR T cell-mediated toxicity observed in the clinical trials of these products.

Obe-cel has been designed to reduce toxicity but still sustain durable CRs.

Obe-cel Phase 1 Clinical Trial in Pediatric ALL

The CARPALL trial was initiated by UCL in the second quarter of 2016 and is a single-arm, open label, multi-center Phase 1 trial enrolling patients aged 24 years or younger with high-risk relapsed or refractory CD19 positive B-lineage ALL.

The main objective of the trial is to evaluate the safety and efficacy of obe-cel when administered at a single dose of 1 million cells/kg.

The trial has completed enrollment with obe-cel.

However, the extension arm is now open, and treating pediatric ALL patients with AUTO 1/22

As of the final data cut-off date of November 22, 2019, the obe-cel arm of the CARPALL trial had enrolled a total of 25 patients, in two cohorts;

one cohort utilized a manual manufacturing process (cohort 1) and one cohort utilized a semi-automated fully enclosed manufacturing process (cohort 2).

Product was generated for 14 of 17 patients in cohort 1 and the median follow-up for the 14 treated patients was 23 months.

Seven patients were treated in cohort 2.

The aim of cohort 2 was to increase feasibility of manufacture at scale;

one patient died before infusion and product was generated for 100% of patients.

Median follow-up for patients in cohort 2 was seven months.

None of the patients experienced Grade 3 or higher CRS and one patient out of 21 patients (5%) experienced Grade 4 neurotoxicity, which was deemed more consistent with fludarabine than CAR-associated neurotoxicity.

Two patients experienced Grade 5 sepsis and death, one in the context of progressive disease and the second was considered related to obe-cel.

This patient was in MRD-negative CR and had ongoing Grade 4 cytopenia associated with resistant HSV encephalitis.

Thirteen patients experienced Grade 4 cytopenias that were ongoing at day 28.

Nineteen of 21 treated patients (90%) achieved molecular CR at post-infusion.

Consistent with preclinical results, CAR T cell expansion and persistence was excellent and CARs were detectable by flow for up to 36 months in four patients in cohort 1 who had ongoing responses beyond 12 months.

Persistence was noted in 15 of 21 patients at last follow-up, up to 36 months.

All of the patients in cohort 2 achieved molecular CR at one month post-infusion.

For cohort 1, with a median follow-up of 23 months, the OS at six and 12 months was 86% and 71%, respectively, and event-free survival at six and 12 months was 71% and 54%, respectively.

In cohort 2, at a median follow-up of 7 months, five patients remain in complete molecular remission and two patients relapsed.

Five of eight evaluable relapses in cohort 1 and cohort 2 combined were due to CD19 negative escape.

In December 2023, Autolus initiated a phase 1 study to evaluate the safety and efficacy of obe-cel in pediatric patients with r/r B-ALL and r/r B-NHL.

This is a single-arm, open label, multi-center trial enrolling patients aged 18 and younger.

The study is currently enrolling patients.

Obe-cel Phase 1b Clinical Trial in Pediatric B-ALL

In December 2023, Autolus initiated the Phase 1b CATULUS trial to evaluate the safety and efficacy of obe-cel in pediatric patients with r/r B-ALL and r/r B-NHL.

This is a single-arm, open label, multicentre trial enrolling patients aged 18 and younger.

The CATULUS trial is a single-arm, open-label, multi-center Phase 1 study enrolling high-risk patients under age 18 with r/r B-ALL that is primary refractory, in high-risk first relapse, or in second or later relapse.

At the ASH annual meeting in December 2025 initial data from the study were presented.

The safety profile of obe-cel in pediatric patients was consistent with that previously reported in adults, with low rates of high-grade CRS and ICANS (both 8.7%).

The ORR was high at 95.5% (n=21), with 90.9% (n=20) achieving complete response (CR).

Twenty patients were in ongoing remission at data cut-off with a median follow-up of 8.8 months.

These preliminary findings support further exploration of obe-cel in pediatric R/R B-ALL.Currently, the Phase 2 pivotal expansion cohort is open for enrollment in the US, UK and Spain.

In October 2025, FDA granted regenerative medicine advanced therapy (RMAT) designation to obe-cel for the treatment of pediatric patients with r/r B-ALL.

The RMAT designation is a program created under the 21st Century Cures Act to accelerate development and regulatory review of regenerative medicine therapies, including cell therapies, intended to treat serious or life-threatening diseases.

The data reported from the CATULUS trial are consistent with previous data reported in the academic UCL-led CARPALL trial in patients aged 24 years or younger with high-risk relapsed or refractory CD19 positive B-ALL, which were published in the journal Nature Medicine in 2019.

Obe-cel Phase 1 Clinical Trial in other B-cell malignancies (ALLCAR19 and CAROUSEL Trials)

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• 20 patients with relapsed or refractory indolent B-NHL (either FL, MCL or marginal zone lymphoma).

At the ASH 2023 meeting, updates were provided from the B-cell NHL/CLL cohorts.

As of the data cut-off date of September 13, 2023, 23 r/r B-NHL and 5 B-CLL patients had received treatment with obe-cel.

Obe-cel continues to display a favorable tolerability profile with no ICANS or Grade 3 or higher CRS across different indications.

Of 28 patients with NHL/CLL evaluable for efficacy, the best ORR was 26/28 (92%).

Obe-cel was observed to be well-tolerated and active in DLBCL, 8/9 evaluable patients entered CMR;

6 patients are in ongoing CMR with one relapse at 12 months and one unrelated death.

In CLL, four of the five treated patients achieved undetectable minimal residual disease ( “ uMRD ” ) in the bone marrow, with all ongoing at the last follow-up date.

We continue to evaluate obe-cel's potential to address current unmet medical needs in these indications.

Our collaborators at UCL have submitted a full manuscript of all 40 patients treated in the extension cohorts to the journal Blood in January 2026.

The abstract of this manuscript states the following:

• 40 received obe-cel (10 patients per disease group).

No patients experienced ≥grade 3 cytokine release syndrome and 1/40 (3%) experienced grade 3 neurotoxicity.

Overall response rate was 36/39 (92%).

PFS at 6 and 12 months was 87% (95% confidence interval [CI], 72–94) and 76% (95% CI, 60–87), respectively.

Excellent expansion (geometric mean Cmax:

113,047 copies/µg genomic DNA) and CAR T persistence were observed (19/23 patients alive and progression-free at last follow-up).

Obe-cel has a good safety profile, high remission rates and durable responses in r/r adult B-cell cancers beyond B-ALL.

Preliminary data support further development of obe-cel for these indications.

• The median follow-up of the entire extension cohorts was 24.2 months (range, 1.3–48.4).

The median follow-up for the different cohorts was as follows:

Median observed follow-up post-infusion was 36.1 months (range, 1.4-39.4).

Median follow-up from infusion was 47.8 months (range, 18.2-48.4).

Median follow-up from infusion was 18.8 months (range, 3.9-48.0).

Median observed follow-up from infusion was 15.1 months (range, 1.3-36.5).

UCL has also initiated a Phase 1 exploratory trial (CAROUSEL) of obe-cel in patients with relapsed or refractory PCNSL.

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Two patients died from progressive PCNSL while part of the study.

We expect to report longer follow-up from this trial and enrollment of additional patients is ongoing.

We expect to report longer follow-up from this trial and enrolment of additional patients is ongoing.

Obe-cel for Lupus and Other Autoimmune Diseases

In addition to advancing AUCATZYL/obe-cel for oncology indications, we are advancing obe-cel for the treatment of Lupus and other autoimmune diseases.

We have initiated the Phase 1 CARLYSLE trial to determine the safety, tolerability, and preliminary efficacy of obe-cel in patients with severe, refractory systemic lupus erythematosus.

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.

In addition to advancing AUCATZYL/obe-cel for oncology indications, we are advancing obe-cel for the treatment of autoimmune diseases.

We have initiated a Phase 1 clinical trial in patients with severe, refractory systemic lupus erythematosus.

We have initiated a Phase 2 clinical trial in patients with severe, refractory lupus nephritis and we have initiated a Phase 1 clinical trial in patients with progressive Multiple Sclerosis.

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.

In some cases SLE can be life threatening.

The disease onset is generally between the ages of 20 and 40, and it affects predominantly young women.

The estimated prevalent population of SLE patients in the United States, United Kingdom, Germany, France Spain, Italy and Japan is approximately 550,000 patients ~60% (330,000 patients) with moderate to severe disease.

~15% will be refractory to standard therapies;

In some cases SLE can be life threatening and chronic disease can be life shortening.

The disease onset is generally between the ages of 20 and 40, and it affects predominantly women.

The estimated prevalent population of SLE patients in the United States, United Kingdom, Germany, France Spain, Italy and Japan is approximately 550,000 patients, of which approximately 60% (330,000 patients) experience moderate to severe disease.

Roughly 15% will be refractory to standard therapies;

potentially addressable by CAR T therapy.

Currently available treatments are not curative and are associated with certain safety concerns.

Many patients require life-long immunosuppression, often with high-dose corticosteroids, cyclophosphamide, or mycophenolate mofetil, non-specifically targeting the immune system to reduce inflammation.

Many patients require life-long immunosuppression, often with high-dose corticosteroids, cyclophosphamide, or mycophenolate mofetil, which reduce inflammation by non-specifically targeting the immune system.

This results in low-level disease activity in only 25–44% of patients in the long term, while sustained complete remission is rare.

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 .

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.

This substantiates the need for developing better strategies to treat SLE .

These outcomes, together with the inability to reverse disease progression support the need for developing better strategies to treat SLE.

Autoreactive B cells with autoantibody formation play a key role in the pathogenesis of SLE.

However, B cell depleting agents, such as the anti-CD20 antibody rituximab, did not improve clinical outcomes compared to placebo in randomized studies in SLE and LN while two different biologics have recently been approved in SLE:

However, B cell depleting agents, such as the anti-CD20 antibody rituximab, did not statistically improve clinical outcomes compared to placebo in randomized studies in SLE and LN.

Three different biologics have recently been approved in SLE:

• Belimumab, an anti-BAFF/BLyS monoclonal antibody, has been approved as add-on therapy in adult patients with active, autoantibody-positive SLE with a high degree of disease activity despite standard therapy.

• Anifrolumab, a type I interferon (“IFN”) receptor antagonist, has also been approved in the United States and EU and is indicated as an add-on for the treatment of adult patients with moderate to severe SLE who are receiving standard therapy.

• Obinutuzumab, a next-generation anti-CD20 B-cell depleting IgG, has been approved by the FDA for patients with LN in combination with standard of care therapy.

Despite these approvals, some patients have insufficient response, lack of response, or lack of sustained response and are at risk for further organ damage despite standard therapy.

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We believe obe-cel's potential advantages over other autoimmune therapies that are approved or in development include its differentiated mechanism of action via its fast-off rate CD19 binder, the existing clinical data and approval in r/r B-ALL and our established manufacturing and commercial capabilities.

In particular, the favorable safety profile, with low rates of high-grade CRS and ICANS in the cancer setting, have the potential to drive acceptability of a cell therapy approach in the rheumatology setting.

Additionally, the fast-off rate kinetics observed with obe-cel in the cancer setting show increased T-cell engraftment and profound B-cell depletion.

In particular, the favorable safety profile in adult r/r B-ALL observed in the FELIX study, with low rates of high-grade CRS and ICANS in the cancer setting, have the potential to drive acceptability of a cell therapy approach in the rheumatology setting.

Additionally, the fast-off rate kinetics observed with obe-cel show increased T-cell engraftment and profound B-cell depletion in B-cell malignancies.

These properties have the potential to drive a deeper cut into CD19+ B cells and plasma blasts in SLE-affected tissues, and could potentially trigger an immune reset in patients.

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Clinical Development in SLE, LN and other Autoimmune Diseases

Obe-cel in SLE and LN

The CARLYSLE trial is a single-arm, open-label, Phase 1 trial to determine the safety, tolerability, and preliminary efficacy of obe-cel in patients with severe , refractory SLE.

The primary goal of this trial is to confirm the fixed dose of obe-cel in adult SLE patients.

Six patients received a target dose of 50 x 106 CD19 CAR- positive T cells.

Beyond this initial cohort, the study has the option to add further cohorts of patients.

The first CARLYSLE trial was initiated in early 2024 and we completed patient doing in early 2025.

We expect to provide initial data at our R&D Investor Event in April 2025 and follow up presentation of full data at a medical conference in the second half of 2025.

Depending on the outcome of the dose confirmation study in SLE, we would plan to initiate further studies in SLE and LN.

Data from the ongoing Phase 1 CARLYSLE study evaluating obe-cel in patients with severe refractory systemic lupus erythematosus was presented at the ASH Annual Meeting in December 2025.

Nine adult patients were infused with obe-cel, including six at the 50M dose and three at the 100M dose.

Obe-cel was well tolerated in all patients.

No dose limiting toxicities (DLTs) or cases of ICANS were observed at the 50M dose.

Grade one cytokine release syndrome (CRS) was observed in three patients at the 50M dose and three patients at the 100M dose.

Hypertension was observed in five patients at the 50M dose, with three of those patients having pre-existing history of hypertension.

A case of transient Grade three liver toxicity was observed in one patient of the 100M cohort.

At the 50M dose, three patients (50%) achieved CRR (Complete Renal Response) and five patients (83%) achieved DORIS (Definition of Remission in SLE) with a median onset of 5.1 months (range:

4.9–8.9), without evidence of new disease activity at a median of 12 months of follow up (range:

All non-renal manifestations of the disease resolved by month four.

Urinary protein creatinine (UPC) ratio levels decreased over time, demonstrating significant decline or absence of disease activity.

Data show high peak expansion and deep B cell aplasia consistent with known obe-cel characteristics in oncology indications.

Peak expansion was reached at a median of 10 days (range:

The median time to loss of CAR T-cell persistence based on Kaplan-Meier analysis was 3.0 months.

The B-cell reconstitution profiles suggest that obe-cel may induce a reset of pathologic autoimmunity.

Emerging data in the 100M cohort is consistent with the 50M adult cohort, and evaluation is ongoing.

We have recently transitioned this program into a Phase 2 potentially pivotal study known as LUMINA, following successful preliminary results from the Phase 1 CARLYSLE trial.

50M has been selected as the recommended Phase 2 dose.

The objective of the study is to assess the safety and effectiveness of a single infusion of obe-cel in patients with severe, refractory systemic lupus erythematosus (SLE) with active lupus nephritis (LN) in participants age 12-65.

The endpoints will be the proportion of participants achieving a complete renal response (signs of kidney inflammation disappearing) and DORIS.

The study is a single-arm, open-label trial involving approximately 30 participants .

Autolus has aligned with FDA on a Phase 2 trial design in LN and potential registrational path to approval.

The LUMINA Phase 2 trial is now enrolling.

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.

Depending on the outcome of the dose confirmation study in SLE, we intend to investigate obe-cel in additional autoimmune disease indications.

Other autoimmune indications include patients with MS.

The phase 1 study in MS (BOBCAT) is currently ongoing.

Obe-cel in progressive multiple sclerosis (“MS”)

Background to progressive MS

In MS, the body’s immune system attacks the myelin sheath or the cells that produce and maintain it (demyelination).

This attack causes an inflammation and injury to the myelin sheath.

Ultimately, the nerve fibers and the myelin sheath surrounds are damaged.

In general, the myelin sheath protects nerves in the brain and spinal cord.

MS encompasses relapsing-remitting MS (“RRMS”), in which a patient may recover either partially or fully, and progressive MS (“PMS”) (either primary PMS (“PPMS”) or secondary PMS (“SPMS”)), in which a patient’s condition steadily declines.

SPMS is associated with higher incidence of hospitalization, as well as greater functional impairment and MS symptom severity than RRMS.

PPMS and SPMS are pathophysiologically similar and exhibit similar rates of disease progression.

RRMS and PMS (either PPMS or SPMS) can be further categorized as either active or non-active.

While demyelination is the fundamental pathophysiologic feature of MS, axonal injury and neurodegeneration play important roles in clinical manifestations and development of progressive disability.

There is no cure for MS and new approaches to treating the disease are needed.

In 2021, there were 1.89 million people in the world living with MS according to Global Burden of Disease Study 2021.

This corresponds to 23.9 cases per 100,000 population.

North America and Western Europe sustained the highest prevalence, incidence, DALYs (disability-adjusted life years) and mortality due to MS.

The prevalence of MS in United States was also fairly high (126/100,000), with northern states having higher prevalence rates compared to the southern states.

Currently available therapies are generally effective at treating relapses and relapse-associated worsening, while disability progression meeting the criteria of Progression Independent of Relapse Activity (“PIRA”) is not effectively treated.

Different pathological processes may be involved, and those underlying PIRA are likely to be confined largely to the CNS compartment, which is inaccessible to most available treatments.

Approved treatments for RRMS, which may also be used in some regions such as the United States to treat patients with active (relapsing) SPMS, have the potential for serious long-term safety concerns, e.g., risk of progressive multifocal eukoencephalopathy following treatment with diroximel fumarate, natalizumab, or ocrelizumab;

risk of congestive heart failure and secondary acute myeloid leukemia following treatment with mitoxantrone hydrochloride;

and increased risks of infection, liver injury, and fetal risk following treatment with cladribine or siponimod.

These medications have shown low levels of reduction in disability progression for SPMS, and none are approved in patients with non-active SPMS.

Cladribine is recommended as second-line treatment due to its risks.

Only one drug, the anti-CD20 B cell-depleting agent ocrelizumab, has been approved for PPMS based on a modest 6% absolute reduction in confirmed disability progression.

Ocrelizumab is also effective in reducing relapses in RRMS and active SPMS, but has warnings and precautions for risk of infection, infusion reaction, and malignancy.

Even with the advent of new therapies, there is still a large MS patient population with a significant unmet need for agents that are effective in reducing progression but have fewer safety risks than existing therapies.

This includes patients with PMS, particularly those with non-active disease (without clear relapses for up to two years), and patients exhibiting PIRA.

B cell depletion has proven to be an effective approach for initial treatment of MS, as demonstrated by the efficacy of disease-modifying mAbs targeting the B cell surface antigen CD20, e.g., rituximab, ocrelizumab, ofatumumab, and ublituximab.

The hypothesized mechanism is an eradication of autoreactive B cell clones and a reset of B cell immunity.

However, depletion of circulating B cells by mAbs has limited therapeutic efficacy as they cannot access autoreactive B cells within lymphatic organs, inflamed tissues, and the CNS, leading to incomplete B cell depletion.

The surface antigen CD19 is expressed on a wide spectrum of B cells and B cell precursor cells as well as plasmablasts, which is not the case for other B cell surface antigens (e.g., CD20).

Obecabtagene autoleucel (obe-cel/AUTO1;

AUCATZYL®) targets CD19 and thus has a broader effect on B cells than existing CD20-targeting therapies.

In order for a drug to be efficient in PMS, it has to cross the blood-brain barrier (BBB) in its active form and directly exert its action upon the CNS inflammatory cells (microglia, astrocyte, oligodendrocyte).

Anti-CD20 mAbs do not readily cross the BBB to target.

CD19-targeting chimeric antigen receptor (CAR) T cells, such as obe-cel, can penetrate the CNS compartment and act on pathological cells inside, and therefore have the potential to be a highly effective new treatment modality for MS.

In contrast to monoclonal antibodies, CAR T cells can penetrate actively the blood-brain barrier (BBB).

We know that obe-cel penetrateds the BBB as evidenced in the FELIX study.

Similarly, other CD19 CAR T cells also penetrate the BBB.

Preclinical experimental autoimmune encephalomyelitis murine models provide further support for the use of CD19-targeting CAR T cell therapies in patients with MS.

Early trials of CD19-directed CAR T cell administration in patients with refractory, progressive MS showed an acceptable safety profile.

CAR T cell presence, expansion, and relative enrichment were observed in the cerebrospinal fluid, with no events of Grade ≥ 2 CRS or ICANS.

Intrathecal antibody reduction indicated expansion-dependent effects of CAR T cells on CD19+ target cells in the CNS.

Overall, although long-term follow-up data are required, these early results are encouraging and demonstrate that further exploration of CAR T therapy in this indication is warranted.

Obe-cel Phase 1 Clinical Trial in MS

Autolus is advancing obe-cel into initial clinical development in progressive MS.

The first patient in the BOBCAT trial was dosed in October 2025.

This Phase 1 trial, expected to include up to 18 adult patients, will evaluate the safety, tolerability, and preliminary efficacy of obe-cel in participants with refractory progressive forms of multiple sclerosis.

The primary endpoint is to assess safety and tolerability of obe-cel.

Key secondary endpoints include evaluating the preliminary efficacy of obe-cel using change from baseline in standard efficacy measures.

We plan to provide updates on the initial Phase 1 data in late 2026.

AUTO1/22 Our Programmed T Cell Therapy for the Treatment of ALL, other B-cell malignancies

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AUTO1/22 Phase 1 Clinical Trial in Pediatric ALL (CARPALL Trial)

We commenced a Phase 1 clinical trial in pediatric patients with relapsed or refractory ALL with our next-generation product candidate, AUTO1/22 in the fourth quarter of 2020.

We commenced a Phase 1 clinical trial in pediatric patients with relapsed or refractory ALL with our dual expressing CAR product candidate, AUTO1/22 in late 202 0.

In a publication in Blood in October 2023, we presented data demonstrating a high level of activity, with 83% of patients (10 of 12 patients evaluated) experiencing MRD negative complete remissions, and a favorable tolerability profile in a very challenging patient population.

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Six and 12-month event free survival (EFS) were 75% and 60% respectively .

This study is no longer enrolling patients.

Our T Cell Lymphoma Program

Introduction to AUTO4

We are developing a programmed T cell product candidate, AUTO4, as a potential treatment for T-cell lymphomas.

We are developing this product candidate with a unique targeting approach that is designed to avoid the severe immunosuppression typically associated with the current investigational CAR T-cell therapies which uses a pan t-cell antigen.

for this disease.

T cells have one of two functionally identical genes, known as TRBC1 and TRBC2.

A normal/healthy T cell population contains a mix of cells expressing either TRBC1 or TRBC2.

Both forms are active and provide the body with natural immunity, including antiviral immunity.

Because T-cell lymphomas are clonal tumors that develop from a single T cell, they are either entirely TRBC1-positive or entirely TRBC2-positive.

Currently available products for the treatment of T-cell lymphoma indiscriminately target all T cells, leading to the severe immunosuppression associated with these treatments.

We have designed AUTO4 as a programmed T cell to specifically target and deplete cells expressing TRBC1, while preserving healthy T cells that express TRBC2.

A normal T cell population consists of varying amounts of TRBC1-positive and TRBC2-positive T cells.

Based on the typical distribution of TRBC1-positive and TRBC2-positive T cells, we believe that patients treated with AUTO4 should be left with a population of healthy, functional polyclonal T cells, which provides the immune system of these patients the ability to respond to bacterial and viral infections and other pathogens.

In addition, this product candidate will have a built-in safety switch designed to eliminate the programmed CAR T cells in the event a patient suffers certain serious adverse events related to the CAR T cell therapy, such as CRS or neurotoxicity.

Background of T Cell Lymphoma

Mature T cell lymphomas are aggressive, treatment resistant malignancies that are associated with poor prognosis.

Clinical application of immunotherapeutic approaches has been limited by a lack of target antigens that discriminate malignant from healthy/polyclonal T cells.

T cell lymphoma is a rare and heterogeneous form of NHL, representing approximately 10 to 20% of NHL cases and 3 to 4% of all hematological malignancies.

Most T cell lymphomas are peripheral T cell lymphomas, (PTCL), the initial indication for which we are developing AUTO4.

PTCL generally involves high-grade tumors and occurs at a similar age as aggressive B cell lymphomas, with a relatively high proportion of patients becoming rapidly unwell.

For the majority the PTCL subtypes, the five-year survival rate may range from 18% to 24%.

The three most common subtypes of PTCL are peripheral T cell lymphoma not otherwise specified (“PTCL-NOS”), anaplastic large-cell lymphoma (“ALCL”), and angioimmunoblastic T cell lymphoma (“AITL”), together accounting for approximately 70% of all PTCLs in the United States.

The first-line treatment for PTCL consists of the combination chemotherapy (e.g.

CHOP, consisting of cyclophosphamide, vincristine, doxorubicin and prednisolone).

However, with CHOP chemotherapy, CR rates are low and disease relapse is common.

In many treatment centers, CHOP chemotherapy may be consolidated with autologous or allogenic stem cell transplantation in selected patients.

Little is understood in terms of treatment guidance for the other PTCL subtypes and these lymphomas lack clear treatment guidelines.

A large proportion of T cell lymphoma patients are refractory to or relapse following treatment with standard therapies and there remains a need to develop an effective therapy for this currently unmet medical need.

Unlike B cell lymphomas, T cell lymphomas have not benefited from advances in immunotherapeutic approaches.

This is mainly due to the lack of therapeutic development in T cell lymphomas to identify suitable target antigens to distinguish malignant T cells from normal/polyclonal T cells.

While a similar problem exists with B cell lymphomas, targeting a pan B cell antigen is an acceptable strategy, as the concomitant depletion of the normal B cell compartment is well tolerated, and some targeted approaches may be ameliorated by the administration of immunoglobulin.

In contrast, targeting a pan T cell antigen would result in severe immunosuppression, where there is currently no available rescue medication.

Some competitors that are pursuing this approach are planning to use CAR T cells therapy as a bridging to SCT.

However, this approach would only benefit the transplant eligible patients who may not be the majority of the T cell lymphoma patients.

There is currently no programmed T cell therapy that is being developed as a standalone treatment.

Clinical Development of AUTO4

In the fourth quarter of 2018, we began enrolling patients in a single-arm, open label, multi-center Phase 1/2 clinical trial, Libra T1, in patients with TRBC1 positive PTCL-NOS, AITL and ALCL, the three most common subtypes of PTCL, for which patients have failed, or have relapsed disease following, at least one prior therapy.

We refer to this trial as the LibrA-T1 trial, which was initiated at sites in the U.K.

and Spain in 2018 and 2020 respectively.

Patients were screened for TRBC status of tumor cells using a CE-marked next-generation sequencing ( “ NGS ” ) method prior to full enrollment in the trial.

The main objective of the Phase 1 portion of the trial was to evaluate the safety of AUTO4 and to determine a recommended dose for the Phase 2 portion of the trial.

The main objective of the Phase 2 portion will be to further evaluate the safety of the treatment and evaluate efficacy endpoints, such as ORR and CR rate.

We designed the trial to evaluate up to five dose levels of AUTO4, beginning with a low dose of 25 million AUTO4 cells.

If we do not observe any dose limiting toxicities ( “ DLT ” ), the dose escalation phase of the trial will continue to higher doses of 75 million AUTO4 cells, 225 million AUTO4 cells, 450 million and potentially 900 million AUTO4 cells.

Data from the first 13 patients dosed in the Libra T1 trial was presented at the ICML in June 2023.

At the cutoff date of April 28, 2023, 19 patients were enrolled into the study and 13 were dosed.

Using manufacturing process A, 10 patients were dosed.

Using manufacturing process B, 3 additional patients were dosed.

Among the 13 patients dosed with AUTO4, the treatment was well tolerated with no DLT.

Ongoing responses at 15 and 18 months post-dosing at the highest dose tested (450x106) are encouraging.

Presence of CAR T cells in the lymph nodes of patients suggest fast homing of CAR T cells to the tumor site, despite absence in the blood.

Efficacy data from Process B was not provided given median follow up is <3 months.

This study is no longer enrolling patients.

Our Multiple Myeloma Program

Our collaborators at UCL are currently evaluating an alternative manufacturing process and initiated an extension to the CARPALL Phase 1 clinical trial in a cohort of pediatric patients with relapsed or refractory ALL in 2025.

We expect that they will report the first data from this study in late 2026 .

Our Multiple Myeloma and Light Chain Amyloidosis Program

Introduction to AUTO8

AUTO8 is a next-generation product candidate for multiple myeloma, which comprises two independent CARs for the multiple myeloma targets, BCMA and CD19.

AUTO8 is a next-generation product candidate for multiple myeloma and Amyloid Light-chain (“AL”) amyloidosis.

AUTO8 comprises two independent CARs for the multiple myeloma targets, BCMA and CD19.

We have developed an optimized BCMA CAR which is designed for improved killing of target cell that express BCMA at low levels.

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We believe our programmed T cell product candidate, AUTO8, with its dual-targeting approach, has the potential to lead to higher levels of efficacy and durability of effect compared to other products and redirected T cell therapies that bind to BCMA alone.

Background to light chain (“AL”) amyloidosis

AL amyloidosis is a rare, acquired disorder characterized by the abnormal folding and deposition of light chains, which are fragments of antibodies, as amyloid fibrils in vital organs.

These light chains are produced by a clone of abnormal plasma cells in the bone marrow.

The deposited amyloid causes organ dysfunction and damage, primarily to the heart and kidneys, but also affecting other organs and tissues.

Early diagnosis is crucial to prevent end-stage organ damage, and current available treatments, such as daratumumab, aim to control the light chain-producing plasma cells to slow or halt disease progression and improve quality of life.

BCMA CAR T-cell therapies, originally developed for multiple myeloma, have shown promising initial safety and efficacy in AL amyloidosis patients including rapid reduction of the disease biomarkers and organ responses in clinical trials.

The therapeutic approach has the potential to eliminate the disease-causing plasma cells by targeting the cause of the disease potentially offers longer term outcomes for these patients.

Clinical Development of AUTO8

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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).

At a median follow-up of 6 months we observed 100% ORR, with 3 PR, 1 VGPR, 7 CR/sCR (all evaluable MRD negative).

Two patients remained in ongoing sCR > 12 months.

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The study is ongoing and continues to recruit patients.

In collaboration with UCL, we commenced a Phase 1 clinical trial in patients with relapsed or refractory AL amyloidosis.

We dosed the first patient on the study in October 2025 and we expect to report the first data from this study in late 2026.

Our Solid Tumor Programs

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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.

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.

The addition of these three modules in the AUTO6NG product candidate significantly augmented its function by extending T cell persistence and rendering modified T cells resistant to TGFb- and PD1/PDL1-driven immune inhibition when compared to AUTO6 in vitro.

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.

We presented new preclinical data for AUTO6NG in June 2020 at the American Association for Cancer Research (“AACR ” ) Virtual Annual Meeting 2020.

GD2 was evaluated as a therapeutic CAR T target antigen in SCLC.

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.

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;

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Clinical Development Strategy of AUTO6NG

G D2 is expressed in numerous pediatric and adult tumors including neuroblastoma, osteosarcoma, soft tissue sarcoma, melanoma, astrocytoma and small cell lung cancer (“SCLC”).

GD2 is expressed in numerous pediatric and adult tumors including neuroblastoma, osteosarcoma, soft tissue sarcoma, melanoma, astrocytoma and SCLC.

A Phase 1 clinical trial of AUTO6NG in r/r neuroblastoma was initiated in December 2023 in collaboration with UCL.

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We have retained worldwide commercial rights for our product candidates.

and parts of Europe, i.e.

countries where we expect to obtain a regulatory approval.

countries where we have obtained a regulatory approval.

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 generally expect to launch any of our products that receive regulatory approval in the United States first, followed by the U.K., EU and subsequently in other major markets.

The product option for AUTO1/22 was not exercised as of February 8, 2025 and has expired.

In addition to the Nucleus, we maintain separate manufacturing capabilities for clinical-stage programs separate to The Nucleus (which is used exclusively for commercial manufacturing of AUCATZYL) to support further clinical trials of obe-cel in autoimmune conditions and potentially future hematological indications.

For clinical trial supply, we have established our internal cell and vector manufacturing capacity at the Cell and Gene Therapy Catapult in Stevenage, United Kingdom.

We have a cell manufacturing suite capable of supporting clinical supply operations.

Under the terms of the License and Option Agreement with BioNTech, BioNTech currently has an option to co-promote or co-commercialize AUTO6NG.

We generally expect to launch any of our products that receive regulatory approval in the United States first, followed by the U.K., EU and subsequently in other major markets to the extent commercially feasible.

BioNTech's product option for AUTO1/22 was not exercised and has expired, so we have regained full rights to commercialize AUTO 1/22.

In addition to the Nucleus, which is currently used exclusively for commercial manufacture of AUCATZYL, we maintain separate manufacturing capabilities for our clinical-stage programs.

For clinical trial supply, we have established cell and vector manufacturing capacity at the Cell and Gene Therapy Catapult in Stevenage, U.K., where we maintain a cell manufacturing suite.

Our early-stage programs such as AUTO1/22 and AUTO6NG are manufactured in collaboration with the UCL study teams.

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Our intellectual property estate, which includes in-licensed intellectual property and intellectual property that we own, is designed to provide multiple layers of protection.

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.

A portion of our patent portfolio is directed to certain current product candidates or technologies deployed in certain product candidates, and the remainder of the portfolio is directed to alternative approaches, technologies or modules that are not currently deployed in our current product candidates.

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Europe, Australia, Canada, Japan, China, Brazil, Chile, Israel, India, Republic of Korea, Hong Kong, Mexico, New Zealand, Russian Federation, Singapore, South Africa, Colombia, Peru, Cuba, Indonesia, Malaysia and Philippines.

Our strategy is to develop and obtain additional intellectual property covering innovative manufacturing processes and methods for genetically engineering T cells expressing new constructs with properties that are designed to improve the ability of our programmed T cells to recognize and kill cancer cells.

To support this effort, we have established expertise and development capabilities focused in the areas of T cell programming, preclinical and clinical research and development, and manufacturing and manufacturing process scale-up, and we expect that our ongoing research and development activities will yield additional patentable inventions and patent applications that will expand our intellectual property portfolio.

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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 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).

We will pay BioNTech a low single-digit percentage of annual net sales of obe-cel, including revenues from sales of AUCATZYL, 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.

We expect to make initial payments of the revenue interest to BioNTech in 2025.

In May 2025, we made our initial payments of the revenue share interest to BioNTech, and as of December 31, 2025 we have paid $1.5 million in revenue share interest to BioNTech.

Manufacturing and Commercial Agreement

Under the terms of the BioNTech License Agreement, we granted BioNTech the option to negotiate a joint manufacturing and commercial services agreement pursuant to which the parties may access and leverage each other’s manufacturing and commercial capabilities, in addition to our planned commercial site network and infrastructure, with respect to certain of each parties’ CAR T product candidates, including BioNTech’s product candidate BNT211 (the “Manufacturing and Commercial Agreement”).

The Manufacturing and Commercial Agreement, if entered into, would also grant BioNTech access to our planned commercial site network and infrastructure.

Under the terms of the BioNTech License and Option Agreement, Autolus Limited has agreed to grant BioNTech the option to negotiate a joint manufacturing and commercial services agreement pursuant to which the parties may access and leverage each other’s manufacturing and commercial capabilities, in addition to Autolus’ 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 Services Agreement” or “MCSA”).

The MCSA, if entered into, would also grant BioNTech access to the Company’s commercial site network and infrastructure.

On 6 August 2025, the MCSA option expired unexercised.

Unless earlier terminated, the BioNTech License Agreement will continue for so long as royalties are payable in respect of Binder licensed Products and the revenue interest is payable in respect of obe-cel products.

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Consequently, we paid a regulatory milestone payment of £10.0 million to UCLB.

On July 17, 2025, the European Commission granted marketing approval for AUCATZYL for the treatment of adult patients (26 years and older) with r/r B-ALL which triggered a £6.0 million regulatory milestone payment that we paid during the three months ended September 30, 2025 in accordance with the UCLB Agreement.

Under the terms of the license, we have the right to grant sub-licenses to third parties, subject to certain restrictions.

If we receive any income in connection with such sublicenses, we must pay UCLB a percentage of the income allocable to the value of the sublicensed intellectual property rights ranging from low twenties to mid-single digits, decreasing based on the development expenses incurred by us and the passage of time.

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.

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.

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In addition, UCLB has the right to negotiate with us for the grant of an exclusive license to our improvements to the T cell programming modules we have licensed on terms to be agreed upon at the time.

Competition for Our Product Candidates

The biotechnology and pharmaceutical industries put significant resources in developing novel and proprietary therapies for the treatment of cancer.

Consequently, there are a number of different products available in the indications where Autolus is seeking to launch our products.

These include in-class competitors, such as autologous CAR T cell therapies, and products from different classes, such as bispecific tumor engagers (“BiTEs”), anti-body drug conjugates (“ADC”), antibody treatments and classic small molecular entities (“SME”) anti-tumor agents.

These include in-class competitors, such as autologous CAR T cell therapies, and products from different classes, such as bispecific t-cell engagers, anti-body drug conjugates, antibody treatments and classic small molecular entities anti-tumor agents.

These anti-tumor agents can be given as single agents or are often used in combination.

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Adult patients with relapsed or refractory FL after two or more lines of systemic therapy.

*Indication based on United States Prescribing Information (USPI)

*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.

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.

There is a market for obe-cel in this indication due to its differentiated safety profile when compared to current approved therapies.

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.

Allogeneic products are in early development and, because these products are not made from the patient's own cells, they might be more convenient to deliver, without the need to wait for a product to be manufactured (typical manufacturing times for autologous products are currently 18-25 days).

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.

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.

For additional discussion of competition for AUCATZYL in adult ALL, see "Business - Our Solution:

Advanced T Cell Programming - Competition for AUCATZYL."

CAR T cell therapies are also being evaluated for treatment of autoimmune diseases.

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Initiated Phase 1 and 2 studies in SLE/LN include Cabaletta (CABA 201), Kyverna (KYV 101), Novartis (YTB323), Juno/BMS (CC-97540), Cartesian (Descartes-08).

An emerging area of competition is in vivo or in situ CAR T-cell therapy.

this is where advanced delivery platforms, such as targeted lipid nanoparticles (LNPs), lentiviral vectors, and mRNA, are used to program t-cells directly inside the patient.

This approach if successful would avoid the complexities of engineering cells outside of the patient.

The field is in its infancy with a focus on achieving high expression of the CAR specifically in the patients T cells, minimizing off-target effects, and demonstrating long-term efficacy.

Very early clinical studies in autoimmune diseases and hematologic cancers starting to emerge.

Key players in this field include Umoja Biopharma (VivoVec platform), Capstan Therapeutics (mRNA-LNP), acquired by Abbvie, Interius BioTherapeutics aquired by Kite and EsoBiotec acquired by Astrazeneca.

Government Regulation and Product Approval

As a biopharmaceutical company, we are subject to extensive regulation.

Our programmed T cell product candidates, if approved, will be regulated as biological medicines.

Our programmed T cell product candidates are regulated as biologics.

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.

The FDA categorizes human cell- or tissue-based products as either minimally manipulated or more than minimally manipulated and has determined that more than minimally manipulated products require clinical trials to demonstrate product safety and efficacy and the submission of a BLA, for marketing authorization.

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.

Our product candidates must be approved by the FDA before they may be legally marketed in the United States and by the appropriate foreign regulatory agency before they may be legally marketed in foreign countries.

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The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions.

During the biological product approval process, the FDA also will determine whether a Risk Evaluation and Mitigation Strategy (“REMS”), is necessary to ensure that the benefits of the product outweigh its risks and to assure the safe use of the biological product, which could include medication guides, physician communication plans, or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools.

FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis.

If the FDA concludes a REMS is needed, the sponsor of the BLA must submit a proposed REMS.

The FDA will not approve a BLA without a REMS, if required.

Before approving a BLA, the FDA will inspect the facilities at which the product is manufactured.

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Even with the submission of additional information, the FDA may ultimately decide that the application does not satisfy the regulatory criteria for approval.

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 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.

If a product receives regulatory approval, the approval is limited to the conditions of use (e.g., patient population, indication) described in the application.

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.

If we obtain approval, regulatory authorities may approve any of our product candidates for fewer indications than we request (including failing to approve the most commercially promising indications) or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of that product candidate.

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.

In addition, the FDA may require post marketing clinical trials, sometimes referred to as Phase 4 clinical trials, designed to further assess a biological product’s safety and effectiveness, and testing and surveillance programs to monitor the safety of approved products that have been commercialized.

After approval, many types of changes to the approved product, such as adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements and FDA review and approval.

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.

The FDA may grant deferrals for submission of data or full or partial waivers.

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.

The FDA may grant deferrals for submission of data or full or partial waivers (e.g., because the relevant disease or condition occurs only in adults).

Products that are granted a marketing authorization on the basis of the pediatric clinical trials conducted in accordance with the PSP are eligible for a six-month extension of marketing exclusivity (pediatric exclusivity).

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.

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.

Although physicians may prescribe legally available products for off-label uses, if the physicians deem to be appropriate in their professional medical judgment, manufacturers may not market or promote such off-label uses.

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Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of new warnings and contraindications, and also may require the implementation of other risk management measures.

The subsequent discovery or appearance of previously unknown or underestimated safety or efficacy concerns with a product could negatively affect commercial sales of the product, result in reduced coverage or reimbursement by payors, cause reputational harm, government investigations, and/or lawsuits against us.

Also, new government requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.

Similar post-approval requirements as described above are specified for other countries where a marketing authorization is granted.

Marketing Exclusivity

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

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

The diagnostic test will require separate regulatory approval in addition to the regulatory approval of AUTO4 and AUTO5.

Failure to obtain marketing approval for the diagnostic test could prevent us from commercializing either AUTO4 or AUTO5 unless another similar diagnostic test for distinguishing TRBC1-positive and TRBC2-positive T cell lymphomas is commercially available.

We will be required to obtain coverage and reimbursement for this test separate and apart from the coverage and reimbursement we seek for AUTO4 and AUTO5, if approved.

Similar challenges to obtaining coverage and reimbursement, applicable to our product candidates, will apply to this proprietary diagnostic test.

Different pricing and reimbursement schemes exist in other countries.

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As a result, increasingly high barriers are being erected to the entry of new products.

For example, the U.S.

Department of Health and Human Services (HHS) imposes rebates on many Medicare Part B and Medicare Part D products to penalize price increases that outpace inflation on an annual basis.

In addition, HHS has been empowered to negotiate the price of certain single-source biologics that have been on the market for at least 11 years covered under Medicare as part of the Medicare Drug Price Negotiation Program.

Each year up to twenty (20) products will be selected by HHS for the Medicare Drug Price Negotiation Program.

Products subject to the Medicare Drug Price Negotiation Program are expected to experience a significant reduction in reimbursement from the Medicare program on a per unit basis.

If coverage and adequate reimbursement are not available, or are available only to limited levels, we may not be able to successfully commercialize our current and any future product candidates that we develop, which could have an adverse effect on our operating results and our overall financial condition.

The marketability of any product candidates for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide coverage and adequate reimbursement.

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Additionally, the federal Physician Payments Sunshine Act, created under the ACA, and its implementing regulations, require certain manufacturers of drugs, devices, biologics 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 Centers for Medicare and Medicaid Services (“CMS”), information related to certain payments or other transfers of value provided to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare providers (such as physicians assistants and nurse practitioners) and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, the physicians and teaching hospitals as well as certain ownership and investment interests held by physicians and their immediate family members.

Additionally, similar healthcare laws and regulations in the European Union 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 the U.K.

GDPR, which imposes obligations and restrictions on the collection and use of personal data relating to individuals located in the European Union and the United Kingdom (including health data).

Additionally, there are similar healthcare laws and regulations in the European Union and other jurisdictions, including reporting requirements detailing interactions with and payments to healthcare providers.

Finally, the majority of states also have statutes or regulations similar to the aforementioned federal laws, some of which are broader in scope and apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

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Recently, there have been a number of health reform measures that we expect will have a significant impact on the pharmaceutical industry.

For example, on August 16, 2022, the Inflation Reduction Act of 2022 (“IRA”), was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in ACA marketplaces through plan year 2025.

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

In addition, the IRA (i) directs HHS to negotiate the price of certain high-expenditure, single-source biologics that have been on the market for at least 11 years covered under Medicare (the “Medicare Drug Price Negotiation Program”) and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.

These provisions began to take effect progressively starting in fiscal year 2023.

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

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

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

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

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

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

For example, on July 4, 2025, the One Big Beautiful Bill Act (the “OBBBA”) was signed into law, which narrowed access to ACA marketplace exchange enrollment and declined to extend the ACA enhanced advanced premium tax credits that expired at the end of 2025, which, among other provisions in the law, are anticipated to reduce the number of Americans with health insurance.

The OBBBA also is expected to reduce Medicaid spending and enrollment by implementing work requirements for some beneficiaries, capping state-directed payments, reducing federal funding, and limiting provider taxes used to fund the program.

Congress is considering proposed legislation intended to further reduce healthcare costs with alternatives to replace the expired ACA subsidies.

We expect that additional U.S.

federal healthcare reform measures will be adopted in the future.

Further, there remains heightened Congressional scrutiny in the United States of pharmaceutical pricing practices designed to, among other things, bring more transparency in product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for products.

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

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

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

Raimondo (“Loper Bright”), the U.S.

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

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

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

In addition to the IRA, other federal health reform measures have been proposed and adopted in the United States that could impact cell therapy.

For example, the current administration has announced agreements with several pharmaceutical companies that require the drug manufacturers to offer, through a direct to consumer platform, U.S.

patients and Medicaid programs prescription drug Most-Favored Nation pricing equal to or lower than those paid in other developed nations, with additional mandates for direct-to-patient discounts and repatriation of foreign revenues.

Other recent actions may include, for example, (1) directives to reduce agency workforce;

(2) directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing Most-Favored-Nation pricing for pharmaceutical products;

(3) imposing tariffs on imported pharmaceutical products;

and (4) as part of the Make America Healthy Again (MAHA) Commission’s Strategy Report released in September 2025, working across government agencies to increase enforcement on direct-to-consumer pharmaceutical advertising.

Additionally, the current administration recently called on Congress to enact “The Great Healthcare Plan,” to codify and expand Most-Favored Nation pricing, lower government subsidies to private insurance companies, increase healthcare price transparency, expand pharmaceutical drugs available for over-the-counter purchase, and enact restrictions on pharmacy benefit manager (PBM) payment methodologies, among other things.

In June 2024, the U.S.

Supreme Court’s Loper Bright decision greatly reduced judicial deference to regulatory agencies, which could increase successful legal challenges to federal regulations affecting our operations.

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

Other federal health reform measures have been proposed and adopted in the United States that could impact cell therapy.

Most notably, the previous administration supported and promulgated a rule related to value based payment alternatives in the Medicaid program.

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and the United States and authorities in the EU, including applicable export control regulations, economic sanctions and embargoes on certain countries and persons, anti-money laundering laws, import and customs requirements and currency exchange regulations, collectively referred to as trade control laws.

Compliance with such regulatory requirements may create delays in the introduction of our products in international markets or, in some cases, prevent the export of our products to some countries altogether.

Furthermore, export control laws and economic sanctions may prohibit the provision of certain products and services to countries, governments and persons targeted by sanctions.

Failure to comply with the UK Bribery Act, the FCPA and other anti-corruption laws and trade control laws could subject us to criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses.

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.

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.

Accordingly, we are subject to certain data privacy and security obligations, including U.S.

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

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.

In the past few years, several states within the United States have enacted comprehensive privacy laws that impose certain obligations on covered businesses.

We may in the future become subject to these laws.

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.

Several states within the United States have enacted comprehensive privacy laws that impose certain obligations on covered businesses.

Additionally, we are, and may become in the future, subject to various U.S.

federal and state consumer protection laws which require us to publish statements that accurately and fairly describe how we handle personal data and choices individuals may have about the way we handle their personal data.

Foreign data privacy and security laws (including but not limited to the EU GDPR and UK GDPR) impose significant and complex compliance obligations on entities that are subject to those laws.

As one example, the EU GDPR applies to any company established in the EEA and to companies established outside the EEA that process personal data in connection with the offering of goods or services to data subjects in the EEA or the monitoring of the behavior of data subjects in the EEA.

These obligations may include limiting personal data processing to only what is necessary for specified, explicit, and legitimate purposes;

requiring a legal basis for personal data processing;

requiring the appointment of a data protection officer in certain circumstances;

increasing transparency obligations to data subjects;

requiring data protection impact assessments in certain circumstances;

limiting the collection and retention of personal data;

increasing rights for data subjects;

formalizing a heightened and codified standard of data subject consents;

requiring the implementation and maintenance of technical and organizational safeguards for personal data;

mandating notice of certain personal data breaches to the relevant supervisory authority(ies) and affected individuals;

and mandating the appointment of representatives in the U.K.

and/or the EU in certain circumstances.

Outside the United States, there are numerous data privacy and security laws that apply and may in the future apply to our processing of personal data, including GDPR, under which companies may face temporary or definitive bans on data processing and other corrective actions;

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

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

See the risk factor captioned “We and the third parties with whom we work are subject to stringent and evolving U.S.

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Clinical Trials

In the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014 (“CTR”) which entered into application on January 31, 2022 repealing and replacing the former Clinical Trials Directive 2001/20 (“CTD”).

The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase transparency.

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;

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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.

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.

Additional GCP guidelines from the European Commission, focusing in particular on traceability, apply to clinical trials of ATMPs.

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At the EU level, developers of medicinal products can ask the EMA for scientific advice and protocol assistance at any stage of development and regardless of whether the medicinal product is eligible for the centralized authorization procedure or not.

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.

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.

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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 Committee for Medicinal Products for Human Use (“CHMP”), conducts the initial assessment of a product.

Under the centralized procedure, the EMA’s CHMP, conducts the initial assessment of a product.

The CHMP is also responsible for several post-authorization and maintenance activities, such as the assessment of modifications or extensions to an existing MA.

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.

Accelerated assessment may be granted by the CHMP in exceptional cases, when a medicinal product targeting an unmet medical need is expected to be of major interest from the point of view of public health and, in particular, from the viewpoint of therapeutic innovation.

If the CHMP accepts a request for accelerated assessment, the time limit of 210 days will be reduced to 150 days (excluding clock stops).

The CHMP can, however, revert to the standard time limit for the centralized procedure if it considers that it is no longer appropriate to conduct an accelerated assessment.

A MA has, in principle, an initial validity of five years.

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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.

Once any pending studies are provided, the conditional MA can be converted into a full MA.

However, if the conditions are not fulfilled within the timeframe set by the EMA and approved by the European Commission, the MA will cease to be renewed.

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If a MA is granted for a medicinal product containing a new active substance, that product benefits from eight years of data exclusivity, during which generic MAAs referring to the data of that product may not be accepted by the regulatory authorities, and a further two years of market exclusivity, during which such generic products may not be placed on the market.

The two-year period may be extended to three years if during the first eight years a new therapeutic indication with significant clinical benefit over existing therapies is approved.

The overall ten-year period may, occasionally, be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the MA holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

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Once the MA is obtained in all EU Member States and study results are included in the product information, even when negative, the product is eligible for a six-month extension to the Supplementary Protection Certificate, or SPC, if any is in effect at the time of authorization or, in the case of orphan medicinal products, a two-year extension of orphan market exclusivity.

In the United States, companies developing a new medicinal product must agree to a Pediatric Study Plan, or PSP, with the FDA during development (except for non-oncology medicinal product with an Orphan Drug Designation) and, at the latest, before submission of a marketing authorization application, and must conduct pediatric clinical trials in accordance with that PSP as agreed, unless a deferral or waiver applies (e.g., because the relevant disease or condition occurs only in adults).

The marketing authorization application for the product must include the results of pediatric clinical trials conducted in accordance with the PSP, unless a waiver applies, or a full or partial deferral has been granted.

Manufacturing Regulation

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Such risk-minimization measures or post-authorization obligations may include additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical trials or post-authorization safety studies.

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.

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Promotional activity that does not comply with the SmPC is considered off-label and is prohibited in the EU.

Much like the Anti-Kickback Statute prohibition in the United States, described above, the provision of benefits or advantages to physicians and other health care professionals to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order or use of medicinal products is also prohibited in the EU.

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

Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.

Infringement of related laws could result in substantial fines and imprisonment.

Payments made to physicians and other health care professionals in certain EU Member States must be publicly disclosed.

Moreover, agreements with health care professionals may require prior notification or approval by the health care professional’s employer, his or her competent professional organization and/or the regulatory authorities of the individual EU Member States.

Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines or imprisonment.

Pricing and Reimbursement

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Other EU Member States allow companies to fix their own prices for products but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions.

Such pricing negotiations with governmental authorities can take considerable time after receipt of marketing approval for a product.

Political, economic and regulatory developments may further complicate pricing negotiations.

In addition, some EU Member States may require the completion of additional studies that compare the cost-effectiveness of a particular medicinal product candidate to currently available therapies.

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The outcome of HTA regarding specific medicinal products will often influence the pricing and reimbursement status granted to these medicinal products by the competent authorities of individual EU Member States.

In December 2021, Regulation No 2021/2282 on Health Technology Assessment (“HTA Regulation”) was adopted.

The HTA Regulation is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products, and providing the basis for cooperation at EU level for joint clinical assessments in these areas.

The HTA Regulation has applied from January 12, 2025 although it will enter into force iteratively and initially apply to new active substances to treat cancer and to all advanced therapy medicinal products (ATMPs), it will then be expanded to orphan medicinal products in January 2028, and to all centrally authorized medicinal products as of 2030.

Selected high-risk medical devices will also be assessed under the HTA Regulation as of 2026.

On January 12, 2025, Regulation No 2021/2282 on Health Technology Assessment (“HTA Regulation”) entered into application through a phased implementation.

The Regulation initially applies to new active substances for oncology and ATMPs.

It will be expanded to orphan medicinal products in January 2028, and to all centrally authorized medicinal products as of 2030.

Select high-risk medical devices also came into scope in 2026.

The HTA Regulation is intended to boost cooperation among EU Member States in assessing health technologies, including new medicinal products.

It establishes a framework for EU‑level joint clinical assessments, increasing cooperation among Member States on clinical aspects of health technology evaluation.

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.

The HTA Regulation is intended to harmonize the clinical benefit assessment of HTA across the EU.

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HTA bodies and other national organizations, such as the Scottish Medicines Consortium (“SMC”), the National Institute for Health and Care Excellence (“NICE”), and the All-Wales Medicines Strategy Group, to introduce new pathways supporting innovative approaches to the safe, timely and efficient development of medicinal products, including, effective as of March 31, 2025, relaunching the Innovative Licensing and Access Pathway with more predictable timelines and closer involvement of the National Health Service.

Regulation of Companion Diagnostics

In the EEA, companion diagnostics are deemed to be in vitro diagnostic medical devices (“IVDs”) and are governed by Regulation 2017/746 (“IVDR”), which entered into application on May 26, 2022, repealing and replacing Directive 98/79/EC.

The IVDR defines a companion diagnostic as a device which is essential for the safe and effective use of a corresponding medicinal product to:

(a) identify, before and/or during treatment, patients who are most likely to benefit from the corresponding medicinal product;

or (b) identify, before and/or during treatment, patients likely to be at increased risk of serious adverse reactions as a result of treatment with the corresponding medicinal product.

The IVDR and its associated guidance documents and harmonized standards govern, among other things, device design and development, preclinical and clinical or performance testing, premarket conformity assessment, registration and listing, manufacturing, labeling, storage, claims, sales and distribution, export and import and post-market surveillance, vigilance, and market surveillance.

IVDs, including companion diagnostics, must conform with the general safety and performance requirements (“GSPR”) of the IVDR.

Compliance with these requirements is a prerequisite to be able to affix the CE mark to devices, without which they cannot be marketed or sold in the EEA.

To demonstrate compliance with the GSPR laid down in Annex I to the IVDR, and obtain the right to affix the CE mark, IVD manufacturers must conduct a conformity assessment procedure, which varies according to the type of IVD and its classification.

Apart from low risk IVDs (Class A which are not sterile), in relation to which the manufacturer may issue an EU Declaration of Conformity based on a self-assessment of the conformity of its products with the GSPRs, a conformity assessment procedure requires the intervention of a Notified Body, which is an organization designated by a Competent Authority of an EEA country to conduct conformity assessments.

Depending on the relevant conformity assessment procedure, the Notified Body audits and examines the technical documentation and the quality system for the manufacture, design and final inspection of the medical devices.

The Notified Body issues a CE Certificate of Conformity following successful completion of a conformity assessment procedure conducted in relation to the medical device and its manufacturer and their conformity with the GSPRs.

This Certificate and the related conformity assessment process entitles the manufacturer to affix the CE mark to its medical devices after having prepared and signed a related EC Declaration of Conformity.

Companion diagnostics must undergo a conformity assessment by a Notified Body.

If the related medicinal product has, or is in the process of, been authorized through the centralized procedure for the authorization of medicinal products, the notified body will, before it can issue a CE Certificate of Conformity, be required to seek a scientific opinion from the EMA on the suitability of the companion diagnostic for use in relation to the medicinal product concerned.

For medicinal products that have or are in the process of authorization through any other route provided in EU legislation, the Notified Body must seek the opinion of the national competent authority of an EU Member State.

Brexit and the Regulatory Framework in the United Kingdom

The United Kingdom’s, or U.K., withdrawal from the EU on January 31, 2020, commonly referred to as Brexit, has changed the regulatory relationship between the U.K.

The Medicines and Healthcare products Regulatory Agency, or MHRA, is now the U.K.’s standalone regulator for medicinal products and medical devices.

The United Kingdom is now a third country to the EU.

regulatory framework in relation to clinical trials is governed by the Medicines for Human Use (Clinical Trials) Regulations 2004, as amended, which is derived from the CTD, as implemented into U.K.

national law through secondary legislation.

On January 17, 2022, the MHRA launched an eight-week consultation on reframing the U.K.

legislation for clinical trials, and which aimed to streamline clinical trials approvals, enable innovation, enhance clinical trials transparency, enable greater risk proportionality, and promote patient and public involvement in clinical trials.

Government published its response to the consultation on March 21, 2023 confirming that it would bring forward changes to the legislation.

Government published its response to the consultation on March 21, 2023 confirming that it would bring forward changes to the legislation and such changes were laid in parliament on December 12, 2024.

These resulting legislative amendments will, if implemented in their current form, bring the U.K.

into closer alignment with the CTR.

In October 2023, the MHRA announced a new Notification Scheme for clinical trials which enables a more streamlined and risk-proportionate approach to initial clinical trial applications for Phase 4 and low-risk Phase 3 clinical trial applications.

Regulatory Framework in the United Kingdom

The MHRA, is now the U.K.’s standalone regulator for medicinal products and medical devices.

While the United Kingdom’s regulatory framework for clinical trials was historically based on the Medicines for Human Use (Clinical Trials) Regulations 2004, which implemented the former EU Clinical Trials Directive, this has been significantly reformed by the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024.

The new legislation, which modernizes the United Kingdom's approach to make it a more attractive location for research, includes key features such as:

(i) a risk-proportionate approach, including a notification scheme for lower-risk trials;

(ii) a combined review process integrating ethics committee and regulatory approvals into a single, streamlined pathway;

(iii) enhanced transparency requirements mandating registration of clinical trials in a public registry and publication of trial results within 12 months of trial completion (with scope for deferrals in certain circumstances);

(iv) greater flexibility to support innovation in clinical trial design;

and (v) measures to promote patient and public involvement.

Marketing authorizations in the United Kingdom are governed by the Human Medicines Regulations (SI 2012/1916), as amended.

Since January 1, 2021, an applicant for the EU’s centralized procedure marketing authorization can no longer be established in the United Kingdom.

As a result, since this date, companies established in the United Kingdom cannot use the EU’s centralized procedure.

In order to obtain a United Kingdom MA to commercialize products in the United Kingdom, an applicant must be established in the United Kingdom and must follow one of the United Kingdom national authorization procedures or one of the remaining post-Brexit international cooperation procedures.

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Employees and Human Capital Resources

As of December 31, 2024, we had 647 full-time employees, 65 of whom hold Ph.D.

degrees, as shown in the table below:

As of December 31, 2025, we had 752 full-time employee s, 113 of whom hold Ph.D.

degrees, as sh own in the table below:

At December 31,

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The principal purposes of our equity incentive plans are to attract, retain and motivate selected employees, consultants and directors through the granting of equity-based compensation awards.

As of December 31, 2024.

the Company added the manufacturing function following the BLA approval granted by the FDA.

As of December 31, 2024, the Company added the manufacturing function following the BLA approval granted by the FDA.

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

What changed 10-K

Item 1. Business