What changed in this filing

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Item 1. Business

2025-03-13 compared with 2024-03-14 · 270 added, 248 removed, 722 unchanged (42% of the section changed)

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We believe this key difference will enable us to deliver readily available treatments faster, more reliably, at greater scale, and to more patients.

Earlier this year, we announced our 2024 Platform Vision that we believe will redefine the future of chimeric antigen receptor (CAR) T therapy by leveraging the unique attributes of allogeneic CAR T products.

Under our 2024 Platform Vision we are focusing on four core programs:

Last year we executed our 2024 Platform Vision, which we believe will redefine the future of chimeric antigen receptor (CAR) T therapy by leveraging the unique attributes of allogeneic CAR T products.

In furtherance of that vision, we continue to focus on three core programs:

Large B-Cell Lymphoma (LBCL) :

Potentially groundbreaking ALPHA3 Trial that we believe may leapfrog other CAR T’s and embed cemacabtagene ansegedleucel (cema-cel, previously ALLO-501A) in first line (1L) LBCL treatment in community cancer centers where most newly diagnosed patients seek care.

Chronic Lymphocytic Leukemia (CLL) :

New Phase 1 ALPHA2 Cohort is designed to evaluate cema-cel as a CLL treatment in order to address the limitations of autologous therapies in a disease where poor T cell fitness is a known barrier to efficacy.

Autoimmune Disease (AID) :

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Renal Cell Carcinoma (RCC) :

Ongoing TRAVERSE trial with ALLO-316 seeks to advance scientific innovation underlying the Dagger® technology to optimize CAR T cell expansion and persistence, thereby maximizing the potential of allogeneic CAR T in solid tumors while mitigating treatment-associated inflammatory response.

TRAVERSE trial with ALLO-316 seeks to advance scientific innovation underlying the Dagger® technology to optimize CAR T cell expansion and persistence, thereby maximizing the potential of allogeneic CAR T in solid tumors while mitigating treatment-associated inflammatory response.

Our allogeneic approach involves engineering healthy donor T cells, which we believe will allow for the creation of an inventory of off-the-shelf products that can be delivered to a larger portion of eligible patients throughout the world.

These potential benefits led our Executive Chair, Arie Belldegrun, M.D., FACS, who was previously the Chair and Chief Executive Officer at Kite Pharma (Kite, now a Gilead company), and our President and Chief Executive Officer, David Chang, M.D., Ph.D., previously Chief Medical Officer and Executive Vice President of Research and Development at Kite, to found our company with the driving purpose of accelerating the development of allogeneic CAR T cell therapies.

Although we are currently focusing on our four core development programs noted above, we continue to have a deep pipeline to further the research and development of allogeneic CAR T cell product candidates in both hematological malignancies and solid tumors.

These potential benefits led our Executive Chair, Arie Belldegrun, M.D., who was previously the Chair and Chief Executive Officer at Kite Pharma (Kite, now a Gilead company), and our President and Chief Executive Officer, David Chang, M.D., Ph.D., previously Chief Medical Officer and Executive Vice President of Research and Development at Kite, to found our company with the driving purpose of accelerating the development of allogeneic CAR T cell therapies.

Although we are currently focusing on our three core development programs noted above, we continue to have a deep pipeline to further the research and development of allogeneic CAR T cell product candidates in both hematological malignancies and solid tumors.

We believe our technology platform combined with our management team’s experience in immuno-oncology and specifically in CAR T cell therapy will help drive the rapid development and, if approved, the commercialization of potentially curative therapies for patients with aggressive cancer or who suffer from autoimmune diseases.

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(Cellectis), TALEN® gene-editing technology to limit the risk of GvHD by engineering T cells to lack functional T cell receptors (TCRs), thereby preventing them from recognizing a patient’s normal tissue as foreign.

With the goal of enhancing the expansion and persistence of our engineered allogeneic T cells, we use

TALEN® technology to inactivate the CD52 gene in donor T cells and an anti-CD52 monoclonal antibody to deplete CD52 expressing T cells in patients while sparing the therapeutic allogeneic T cells.

With the goal of enhancing the expansion and persistence of our engineered allogeneic T cells, we use TALEN® technology to inactivate the CD52 gene in donor T cells and an anti-CD52 monoclonal antibody to deplete CD52 expressing T cells in patients while sparing the therapeutic allogeneic T cells.

We believe this enables a window of persistence for the infused allogeneic T cells to actively target and destroy cancer cells.

We are also developing ALLO-647, our own anti-CD52 monoclonal antibody, which is designed to be used prior to infusing our other product candidates as part of a lymphodepletion regimen.

We are also developing ALLO-647, our own anti-CD52 monoclonal antibody, which is designed to be used prior to infusing our other product candidates as part of a

lymphodepletion regimen.

Our off-the-shelf approach is dependent on state-of-the-art manufacturing processes, and we believe we have built a technical operations organization with fully integrated in-house expertise in clinical and commercial engineered T cell manufacturing.

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Our most advanced product candidate, cemacabtagene ansegedleucel, referred to as cema-cel (previously ALLO-501A), is an engineered allogeneic CAR T cell product candidate that targets CD19, a protein expressed on the cell surface of B cells and a validated target for B cell driven hematological malignancies.

We are currently focused on developing cema-cel for LBCL and CLL.

We are currently focused on developing cema-cel for LBCL.

Our pipeline also includes ALLO-316 and ALLO-329.

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We are currently focused on developing ALLO-316 for RCC.

ALLO-329, an engineered allogeneic CAR T cell product candidate that targets both CD19 and CD70, is in development for the treatment of certain AIDs.

We also have additional product candidates, but we have deprioritized these programs to allow us to focus on cema-cel, ALLO-316 and ALLO-329.

ALLO-329, an engineered allogeneic CAR T cell product candidate that targets both CD19 and CD70, is in development for the treatment of systemic lupus erythematosus (SLE), idiopathic inflammatory myopathies (IIM), and systemic sclerosis (SSc).

We have additional product candidates, but we have deprioritized these programs to allow us to focus on cema-cel, ALLO-316 and ALLO-329.

Our pipeline is represented in the diagram below.

1 Phase 3 may not be required if Phase 2 is registrational

2 ALLO-647 (anti-CD52 mAb) is intended to enable expansion and persistence of allogeneic CAR T product candidates

1 Phase 2 designed to be registrational

Our lead product candidates include:

• Cemacabtagene ansegedleucel (cema-cel).

We are currently focused on developing cema-cel in LBCL and CLL.

We plan to initiate a pivotal Phase 2 clinical trial (ALPHA3) in mid-2024 for cema-cel as part of a 1L treatment plan for newly diagnosed and treated LBCL patients who are likely to relapse and need further therapy.

We are enrolling a pivotal Phase 2 clinical trial (ALPHA3) for cema-cel as part of a 1L treatment plan for newly diagnosed and treated LBCL patients who are likely to relapse and need further therapy.

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The ALPHA3 trial is designed to study the impact of treating MRD positive patients with cema-cel.

The study will randomize approximately 230 patients who achieve a complete response or partial response to 1L therapy, but who are MRD positive.

The patients will be randomized to either consolidation with cema-cel or the current standard of care, which is observation.

The design, with a primary endpoint of event free survival (EFS), will initially include two lymphodepletion arms (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one with standard fludarabine and cyclophosphamide but without ALLO-647).

One lymphodepletion arm will be discontinued following a planned interim analysis in mid-2025 designed to select the most appropriate regimen for this patient population.

In view of the potential of the earlier line ALPHA3 trial, we have deprioritized the third line (3L) LBCL ALPHA2 and EXPAND trials.

We have initiated the Phase 1b cohort of our ALPHA2 trial to evaluate cema-cel following lymphodepletion with fludarabine/cyclophosphamide and ALLO-647 in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

This cohort will include up to 40 patients, and we expect to release initial data by year-end 2024.

We are enrolling a Phase 1 clinical trial (TRAVERSE) of ALLO-316, an allogeneic CAR T cell product candidate targeting CD70, in adult patients with advanced or metastatic RCC.

We presented interim results from the TRAVERSE trial at the American Association of Cancer Research (AACR) Annual Meeting in April 2023.

The study will randomize

approximately 240 patients who achieve a complete response or partial response to 1L therapy, but who are MRD positive.

Patients will be randomized to receive either consolidation with cema-cel or the current standard of care, which is observation.

The study design, which has event free survival (EFS) as its primary endpoint, initially includes two lymphodepletion arms:

standard fludarabine and cyclophosphamide plus ALLO-647

standard fludarabine and cyclophosphamide without ALLO-647

One of these lymphodepletion arms will be discontinued following a planned interim analysis designed to identify the most appropriate regimen for this patient population.

An initial safety and futility interim analysis will occur once 12 patients in each arm have been enrolled and followed for MRD conversion.

If both treatment arms perform better than the control arm according to the futility criteria, but neither treatment arm shows a trend toward superiority relative to the other in this interim analysis, additional patients may be enrolled and analyzed before we select the final lymphodepletion regimen.

The selection of the lymphodepletion regimen is anticipated around mid-2025, depending on the interim analyses results and overall trial progress.

We have completed enrollment in a Phase 1 clinical trial (TRAVERSE) of ALLO-316, an allogeneic CAR T cell product candidate targeting CD70, in adult patients with advanced or metastatic RCC.

We presented interim results from the TRAVERSE trial at the International Kidney Cancer Symposium (IKCS) and The Society for Immunotherapy of Cancer's (SITC) Annual Meeting in November 2024.

See “—Product Pipeline and Development Strategy—Anti-CD70 Development Program—Results from the Phase 1 ALLO-316 TRAVERSE Trial” for information regarding the results.

We have implemented a protocol amendment that incorporates a diagnostic and treatment algorithm into the study design.

The algorithm is designed to mitigate the treatment-associated hyperinflammatory response without compromising the CAR T function needed to eradicate solid tumors.

The next update from this trial is planned for a publication in the second quarter of 2024 and will discuss the algorithm.

A more comprehensive data update from the ongoing trial with the updated protocol is planned for year-end 2024.

We are developing ALLO-329, a next-generation allogeneic CAR T cell product candidate targeting both CD19 and CD70 for the treatment of certain autoimmune diseases.

Inclusion of an anti-CD70 CAR in ALLO-329 incorporates the Dagger® technology, which is designed to reduce or eliminate the need for standard chemotherapy by preventing premature rejection while targeting CD19+ B-cells and CD70+ activated T-cells, both of which play a role in AID.

Initiation of this Phase 1 trial with ALLO-329 is expected in early 2025.

We are developing an anti-CD52 monoclonal antibody, ALLO-647, which is a proprietary component of our lymphodepletion regimen.

ALLO-647 may be able to reduce the likelihood of a patient’s immune system rejecting the engineered allogeneic T cells for a sufficient period of time to enable a window of persistence during which our engineered allogeneic T cells can actively target and destroy cancer cells.

During Part A of our pivotal ALPHA3 trial, we will be assessing ALLO-647’s contribution to the overall benefit to risk ratio of the lymphodepletion regimen for cema-cel.

Patients will be randomized to receive cema-cel and a lymphodepletion regimen with fludarabine and cyclophosphamide either with or without ALLO-647.

We plan to select the lymphodepletion regimen in mid 2025.

In October 2024, we announced that we received Regenerative Medicine Advanced Therapy (RMAT) designation for ALLO-316 for adult patients with advanced or metastatic RCC.

The RMAT designation was based on Phase 1 clinical data from the TRAVERSE trial indicating the potential of ALLO-316 to address the unmet need for patients with difficult-to-treat RCC who have failed multiple standard RCC therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.

Once we have obtained additional follow-up data on the enrolled patients, we plan to engage with FDA to establish the next steps for this development program.

Following the clearance of an IND in January 2025, we plan to initiate a Phase 1 clinical trial (the RESOLUTION trial) of ALLO-329, an allogeneic CAR T cell product candidate targeting both CD19 and CD70, in adult patients with systemic lupus erythematosus, including lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis in mid-2025.

The RESOLUTION trial will include two distinct lymphodepletion arms:

one using a dose of cyclophosphamide alone which is used by rheumatologists, and another that eliminates lymphodepletion entirely.

• Other Product Candidates:

While we have additional programs in our pipeline, our development priorities are focused on cema-cel (1L Consolidation and CLL), ALLO-316, and ALLO-329.

While we have additional programs in our pipeline, our development priorities are focused on cema-cel (1L Consolidation in LBCL), ALLO-316, and ALLO-329.

We will explore opportunities to partner with collaborators on product candidates across our pipeline.

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(Pfizer), including strategic license and collaboration agreements and other intellectual property related to the development and administration of allogeneic CAR T cells for the treatment of cancer.

We have an Exclusive License and Collaboration Agreement (the Servier Agreement) with Les Laboratoires Servier SAS and Institut de Recherches

Internationales Servier SAS (collectively, Servier) to develop and commercialize cema-cel, and we hold the commercial rights to these product candidates in the United States.

We have an Exclusive License and Collaboration Agreement (the Servier Agreement) with Les Laboratoires Servier SAS and Institut de Recherches Internationales Servier SAS (collectively, Servier) to develop and commercialize cema-cel, and certain additional product candidates, and we hold the commercial rights to these product candidates in the United States, the European Union, and the United Kingdom.

The Servier Agreement gives us access to Cellectis’ TALEN® gene-editing technology for cema-cel.

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Zachary Roberts, was also instrumental in the development and execution of the clinical trials of Yescarta® across multiple indications.

Our Chief Technical Officer, Timothy Moore, has over 30 years of leadership experience in biopharmaceutical manufacturing and operations and was previously Executive Vice President, Technical Operations at Kite, where he was responsible for the process development, manufacturing, quality and supply chain for Yescarta ® .

Our goal is to maintain and build upon our leadership position in allogeneic CAR T cell therapy.

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• Repositioning our allogeneic CAR T product as the only CAR T to be part of a first-line (1L) consolidation approach.

As described in our 2024 Platform Vision, we seek to redefine the future of CAR T by potentially repositioning our allogeneic CAR T product as the only CAR T to be part of a first line (1L) treatment plan for newly diagnosed and treated LBCL patients who are likely to relapse and need further therapy.

We seek to redefine the future of CAR T by potentially repositioning our allogeneic CAR T product as the only CAR T to be part of a first line (1L) treatment plan for newly diagnosed and treated LBCL patients who are likely to relapse and need further therapy.

The design of the ALPHA3 1L consolidation trial builds upon the results demonstrated in the Phase 1 ALPHA2 trial and leverages an investigational diagnostic test developed by Foresight Diagnostics to identify patients who have MRD at the completion of 1L chemoimmunotherapy for treatment with cema-cel.

Start-up activities for the ALPHA3 trial are underway and the trial is expected to begin enrolling in mid-2024.

The ALPHA3 trial was initiated in June 2024 and now has 40 sites activated and screening for patients with MRD.

An interim analysis is anticipated around mid-2025 depending on the analyses and overall trial progress, and based thereon, the lymphodepletion regimen for the remainder of the trial will be selected.

• Expand our allogeneic CAR T platform into the treatment of autoimmune disease (AID).

We are currently developing a next-generation product candidate, ALLO-329, which is an engineered allogeneic CAR T cell product candidate that targets CD19 and CD70.

ALLO-329 incorporates our Dagger® technology.

In January 2025, we announced that the FDA has cleared our IND for a rheumatology basket study of ALLO-329, our RESOLUTION trial.

Incorporation of the Dagger® technology into an “off-the-shelf” CD19 product for use in AID is designed to reduce or eliminate the need for standard chemotherapy while targeting CD19+ B-cells and CD70+ activated T-cells, both of which play a role in AID.

Initiation of the RESOLUTION trial is targeted for mid-2025 with initial proof-of-concept data available anticipated around year-end 2025.

• Build state-of-the-art gene engineering and cell manufacturing capabilities .

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We plan to continue to advance the research and development of ALLO-316, which targets CD70, for the treatment of clear cell renal cell carcinoma (ccRCC) as part of our TRAVERSE trial.

We are investigating next-generation technologies incorporated in the design of ALLO-316 which seek to better control rejection of allogeneic CAR T cells by the patient immune system.

We are investigating next-generation technologies incorporated in the design of ALLO-316 which seek to better control rejection of allogeneic CAR T cells by the patient's immune system.

Such technologies include our Dagger® technology that utilizes an anti-CD70 CAR to kill alloreactive host T cells.

We are also advancing technologies to increase specificity of CAR T activity to avoid potential normal tissue toxicities associated with certain solid tumor targets.

We continually survey the scientific and industry landscape for opportunities to license, partner or acquire technologies that may help us advance current or new cell therapies for the benefit of patients.

• Expand our allogeneic CAR T platform into the treatment of autoimmune disease (AID).

We are currently developing a next-generation product candidate, ALLO-329, which will be an engineered allogeneic CAR T cell product candidate that targets CD19 and CD70.

ALLO-329 will incorporate our Dagger® technology.

We are currently focused on developing ALLO-329 for AID.

Initiation of this Phase 1 trial with ALLO-329 is expected in early 2025.

Allogeneic CAR T Cell Therapy

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CARs are engineered molecules that, when present on the surface of a T cell, enable the T cell to recognize specific proteins or antigens that are present on the surface of other cells.

More than one type of CAR can be included in a CAR T cell, imparting multi-antigen targeting capability.

More than one type of CAR can be included in a CAR T cell,

imparting multi-antigen targeting capability.

The CAR molecule(s) in our product candidates are comprised of a single chain protein that contains the following elements:

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In addition, activated CAR T cells stimulate the local secretion of cytokines and other molecules that can recruit and activate additional immune cells to potentiate killing of the cancer cells.

In addition to the domains described above, in ALLO-316, we have included rituximab recognition domains to potentially serve as a way to identify and/or eliminate ALLO-316 cells using rituximab.

In addition to the domains described above, in ALLO-316, we have included rituximab recognition domains to potentially serve to identify and/or eliminate ALLO-316 cells using rituximab.

The figure below shows the constructs that support our lead product candidates in clinical development:

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autologous and allogeneic.

Autologous therapies use engineered T cells derived from the individual patient, while allogeneic products use engineered T cells derived from unrelated

healthy donors.

Autologous therapies use engineered T cells derived from the individual patient, while allogeneic products use engineered T cells derived from unrelated healthy donors.

While the autologous approach has been revolutionary, demonstrating compelling efficacy in many patients, it is burdened by the following key limitations:

• Lengthy Delivery Time .

Due to the individualized manufacturing process, patients may wait weeks to months be treated with their engineered cells.

Due to the individualized manufacturing process, patients may wait weeks to months to be treated with their engineered cells.

As a result, in the registrational trials for Yescarta® and Kymriah ® , up to 31% of intended patients ultimately did not receive treatment primarily due to complications from the underlying disease prior to delivery of therapy or as a result of manufacturing failures.

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Our allogeneic approach has the potential to create off-the-shelf product inventory, which could enable dosing of patients within days of a decision to treat.

This would represent a significant reduction in patient wait time, potentially obviating the need for any bridging therapy and allowing the treatment of patients who are either too sick, or their disease progresses to quickly for them to wait for their autologous CAR T cells to be manufactured, thus potentially improving patient outcomes.

This would represent a significant reduction in patient wait time, potentially obviating the need for any bridging therapy and allowing the treatment of patients who are either too sick, or their disease progresses too quickly for them to wait for their autologous CAR T cells to be manufactured, thus potentially improving patient outcomes.

In addition, as we seek to incorporate our investigational allogeneic CAR T product into a 1L consolidation strategy, the speed to patient becomes even more important.

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• Streamlined Manufacturing .

We are building an efficient and scalable manufacturing process and organization.

We have built an efficient and scalable manufacturing process and organization.

The allogeneic CAR T approach utilizes healthy donor T cells which we believe provides enhanced scalability, and an off-the-shelf capability that can potentially reduce the costs to the overall healthcare system as it does not require bridging therapy, leukapheresis and complex logistics.

Manufacturing Allogeneic T Cells

There are similarities as well as key differences between the processes for allogeneic and autologous CAR T cell manufacturing, as illustrated in the figure below which depicts our manufacturing process for our oncology CAR-T product candidates.

There are similarities as well as key differences between the processes for allogeneic and autologous CAR T cell manufacturing.

The three primary steps to creating our engineered allogeneic CAR T cells are:

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We start with collecting white blood cells from a healthy donor, which are subsequently stimulated to proliferate and transduced with a viral vector to integrate the CAR sequence into the T cell genome.

The CAR sequence directs the expression of CAR proteins on the cell surface that allows the transduced T cells to recognize and bind to a target molecule that is present on cancer cells.

Next, we use gene editing tools to edit the T cell genome to inactivate TCRα and CD52.

Inactivation of TCRα and CD52 is intended to reduce the risk of GvHD and allow the allogeneic

T cells to expand and persist in patients, respectively.

The CAR sequence directs the expression of CAR proteins on the cell surface that allows the transduced T cells to recognize and bind to a target molecule, for example a target that is present on cancer cells or pathogenic autoreactive immune cells.

Next, we use gene editing tools to edit the T cell genome to inactivate TCRα, and in the case of our oncology products, to also inactivate CD52.

Inactivation of TCRα and CD52 is intended to reduce the risk of GvHD and enable the use of ALLO-647, a proprietary CD52 monoclonal antibody, as part of lymphodepletion to allow the allogeneic T cells to expand and persist in patients, respectively.

For oncology products the transduction and genetic editing steps are separate, but for our autoimmune disease product candidate, ALLO-329, the steps are combined and utilize different gene editing technology.

Furthermore, ALLO-329 does not incorporate the CD52 knockout utilized in oncology products.

Finally, the edited T cells are cultured for several days to increase the cell number, harvested and purified.

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This inventory is securely stored and then shipped to treatment facilities, as needed.

The figure below illustrates the steps in a manufacturing run for our engineered oncology allogeneic CAR T product candidates.

Product Pipeline and Development Strategy

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Our product pipeline is represented in the chart below:

1 Phase 3 may not be required if Phase 2 is registrational;

2 ALLO-647 is intended to enable expansion and persistence of allogeneic CAR T product candidates;

1 Phase 2 designed to be registrational

Anti-CD19 Oncology Development Program

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On September 15, 2022, Servier sent us a notice of discontinuation of its involvement in the development of all CD19 Products pursuant to the Servier Agreement.

While we continue to work to redefine our relationship with Servier, in the interim, we have assumed all responsibility for the CD19 development program.

On May 10, 2024, the we entered into an Amendment and Settlement Agreement (the Servier Amendment) with Servier which restructures our relationship under the Servier Agreement.

Under the Servier Amendment the parties agreed that co-development performed by the Company and Servier under the Servier Agreement, including co-development relating to CD19 Products, ceased as of December 15, 2022.

UCART19 was our first CD19 product candidate, and Servier led its manufacturing and clinical development.

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In addition, UCART19 cells were engineered to express a small protein on the cell surface called RQR8, which consists of two rituximab recognition domains.

This allowed for recognition and elimination of the CAR T cells by rituximab in the event that silencing of CAR T cell activity is desired.

This allowed for recognition and elimination of the CAR T cells by rituximab if silencing of CAR T cell activity is desired.

Servier sponsored two Phase 1 clinical trials of UCART19 in patients with R/R CD19 positive B-cell acute lymphoblastic leukemia (ALL), both of which were completed in 2020.

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Results from the Phase 1 ALLO-501 ALPHA Trial and the Phase 1 cema-cel ALPHA2 Trial

On June 3, 2023, we announced long-term follow up data from the Phase 1 ALPHA trial of ALLO-501 and from the Phase 1 ALPHA2 trial of cema-cel in R/R LBCL at the American Society of Clinical Oncology (ASCO) Annual Meeting.

We conducted an extensive Phase 1 program designed to evaluate and optimize all aspects of our lead product candidate, including the dose and schedule of cema-cel and ALLO-647.

The long-term data included an updated analysis of data from 12 CAR T-naïve patients with R/R LBCL who received a single dose of ALLO-501/cema-cel manufactured using the Alloy™ process following a lymphodepletion regimen (FCA90) comprised of fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) plus ALLO-647 (30 mg/day x 3 days).

The median time from enrollment to the start of therapy was three days and all 12 patients were followed through a minimum of six months (data cutoff April 20, 2023).

The updated data from the Phase 1 trials of ALLO-501 and cema-cel are foundational for our ALPHA3 trial and continue to support the ability of a single administration of allogenic CAR T cells to induce durable complete remissions at a rate similar to approved autologous CD19 CAR T therapies.

Among the 12 patients treated with the single dose FCA90

regimen, the overall response rate (ORR) was 67% and 58% achieved CRs with 42% maintaining CR through month six.

Of the five patients who were in CR at six months, four (80%) remained in CR.

The fifth patient had disease progression at 24 months.

The median duration of response was 23.1 months with three patients remaining in remission for over 24 months and the longest remaining in remission for over 31 months.

On February 13, 2025, we announced long-term follow up data from the Phase 1 ALPHA trial of ALLO-501 and from the Phase 1 ALPHA2 trial of cema-cel in R/R LBCL which was published in the Journal of Clinical Oncology.

The ALPHA/ALPHA2 studies were single-arm, multicenter, open-label, Phase 1 trials.

As of the data cutoff date (September 26, 2024), 33 CD19 CAR T-naive patients with R/R LBCL were treated in ALPHA/ALPHA2 with cema-cel/ALLO-501 manufactured with the process selected for use in pivotal studies.

The overall Response Rate (ORR) and Complete Response (CR) rate in the ALPHA/ALPHA2 trials were comparable with those observed in patients with R/R LBCL after two or more lines of systemic therapy who received treatment with approved autologous CD19 CAR T cell products.

All treatment regimens studied demonstrated clinical benefit.

The selected Phase 2 regimen (fludarabine/cyclophosphamide lymphodepletion with 90 mg of ALLO-647 (FCA90) followed by a single dose of CAR+ cells) yielded the highest ORR and CR of 67% and 58%, respectively.

Five of 12 patients in this group achieved CR that lasted at least 6 months.

Patients Treated with Phase 2 Regimen (n=12)

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6 Month CR Rate, n (%)

The ALPHA and ALPHA2 Phase 1 trials demonstrated a manageable safety profile and treatment was generally well tolerated with no GvHD and no observed dose limiting toxicities (DLTs).

Among patients treated with single dose FCA90, there was no Grade 3+ CRS or neurotoxicity.

One patient (8%) experienced a Grade 3+ infection and two (17%) experienced prolonged Grade 3+ cytopenia.

As previously reported, one Grade 5 event occurred.

No new Grade 5 events have occurred.

All R/R CAR T naïve LBCL

Patients Treated with Phase 2 Regimen

Neurotoxicity

Prolonged Gr3+ Cytopenia

Second Target Indication:

Chronic Lymphocytic Leukemia (CLL)

CLL is also a hematologic cancer originating from malignant lymphocytes.

Within the United States, annually approximately 20,700 new cases of CLL are estimated to be diagnosed with approximately 4,400 deaths estimated to occur according to 2024 figures from the American Cancer Society.

Targeted therapy can be used to treat CLL, including treatment with Bruton tyrosine kinase inhibitors (BTKi) or B-cell lymphoma 2 inhibitors (BCL2i).

Although such frontline therapies can be effective in achieving a remission, CLL remains incurable, and the disease will likely relapse and require further line(s) of therapy.

While recent autologous CD19 CAR T data has been a positive step for patients with R/R CLL, outcomes in CLL following CAR T treatment have yet to meet expectations set in R/R LBCL.

This is likely due in part to T cell dysfunction and the potential for high circulating tumor burden in CLL, making the isolation of functional T cells for autologous CAR T manufacturing difficult.

We believe that our AlloCAR T™ products, such as cema-cel which is derived from healthy donor cells, could potentially create a clinically meaningful advance for these late-stage CLL patients, with a one-time dose and simpler administration and logistics.

Patients who achieved a CR had excellent outcomes with a median DOR, PFS (progression free survival) and OS of 23.1 months, 24 months, and not reached, respectively.

For patients receiving the selected Phase 2 regimen, median DOR was 23.1 months and median OS was not reached.

The safety profile, including incidence of cytopenias and infections, was manageable and consistent with that of approved autologous CD19 CAR T cell therapies.

There were no dose-limiting toxicities, graft-versus-host disease (GvHD), immune effector cell-associated neurotoxicity syndrome (ICANS), or high-grade cytokine release syndrome (CRS).

The most common any-grade treatment emergent adverse events (TEAE) (≥25%) were neutropenia (85%), anemia (67%), thrombocytopenia (58%), infusion-related reactions (IRRs;

58%), fatigue (52%), and pyrexia (49%), nausea (39%), lymphopenia (36%), hypotension (36%), peripheral edema (33%), decreased white blood cell count (30%), CMV reactivation (30%), decreased appetite (30%), chills (30%), and hypoxia (27%).

The median time to start of treatment was two days from study enrollment.

In contrast, autologous CAR T cell products require wait times often longer than 1 month despite incremental advancements in manufacturing and supply chains.

A growing body of evidence indicates that treatment with CAR T at times when the disease burden is low leads to improved safety and efficacy outcomes and this study reported similar findings.

Among patients with baseline tumor burden <1000 mm² or normal serum lactate dehydrogenase (LDH), a blood test that indicates disease activity, the CR rate was 100% (6/6) and 82% (9/11), respectively.

These CR rates in this subpopulation support cema-cel as a promising therapeutic option in patients with minimum residual disease (MRD), the population currently being studied in the ALPHA3 trial.

These results serve as the foundation for the ongoing ALPHA3 trial, which is evaluating cema-cel as a consolidation therapy in LBCL patients who are in remission following 1L treatment but remain positive for MRD as detected by an ultrasensitive ctDNA based blood test, Foresight Diagnostics’ investigational CLARITY™ , powered by PhasED-Seq™.

These patients have extremely low disease burden, a key subgroup who demonstrated excellent disease outcomes in the ALPHA/ALPHA2 trials.

Clinical Development Plan - Non-Hodgkin Lymphoma (NHL)

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In the fourth quarter of 2022, we proceeded to the Phase 2 portion of the ALPHA2 trial in adult patients with R/R LBCL.

We are also sponsoring the EXPAND trial of ALLO-647, which was intended to demonstrate the overall contribution of ALLO-647 to the benefit to risk ratio of the lymphodepletion regimen for cema-cel.

In January 2024 we announced that we would deprioritize the ALPHA2 R/R LBCL and EXPAND trials to focus on our ALPHA3 trial, which will seek to embed cema-cel as part of a 1L consolidation strategy.

We have also sponsored the EXPAND trial of ALLO-647, which was intended to demonstrate the overall contribution of ALLO-647 to the benefit to risk ratio of the lymphodepletion regimen for cema-cel.

In January 2024 we announced that we would deprioritize the ALPHA2 R/R LBCL and EXPAND trials to focus on our ALPHA3 trial, which seeks to embed cema-cel as part of a 1L consolidation strategy.

We have deprioritized the ALPHA2 R/R LBCL trial primarily because the ALPHA3 trial, if successful, could significantly impact the need for cell therapy in later lines of treatment, including the third line (3L) patients being studied in our ALPHA2 trial.

The ALPHA3 trial will be an open-label, Phase 2, multicenter clinical trial evaluating the safety and efficacy of cema-cel in adult patients with

LBCL who have completed R-CHOP and have attained a remission, but who test positive for MRD.

The ALPHA3 trial is an open-label, Phase 2, multicenter clinical trial evaluating the safety and efficacy of cema-cel in adult patients with LBCL who have completed R-CHOP and have attained a remission, but who test positive for MRD.

The ALPHA3 trial will randomize approximately 240 patients who achieve a complete or partial response to 1L therapy, but who test positive for MRD at their end-of-therapy PET/CT assessment.

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The design, with a primary endpoint of EFS, will initially include two lymphodepletion arms (one with standard fludarabine and cyclophosphamide plus ALLO-647 and one without ALLO-647).

One lymphodepletion arm will be discontinued following a planned interim analysis in mid-2025 designed to select the most appropriate regimen for this patient population.

The ALPHA3 trial will leverage an investigational diagnostic test developed by Foresight Diagnostics to identify patients who have MRD at the completion of 1L chemoimmunotherapy.

Although 1L R-CHOP is curative for many with LBCL, as noted above, approximately 30% of patients treated will relapse.

One lymphodepletion arm will be discontinued following a planned interim analysis around mid-2025 designed to select the most appropriate regimen for this patient population.

The ALPHA3 trial leverages an investigational diagnostic test developed by Foresight Diagnostics to identify patients who have MRD at the completion of 1L chemoimmunotherapy.

Although 1L R-CHOP is curative for many with

LBCL, as noted above, approximately 30% of patients treated will relapse.

Under the current standard of care, there is no way to determine which patients are at greater risk of relapse after initially responding to 1L treatment, and so the standard of care has been simply to “watch and wait” for the disease to relapse.

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Cema-cel’s Phase 1 safety profile, with low rates of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), already permits its use in the outpatient setting in R/R patients and may further improve in patients with no radiological evidence of disease.

Start-up activities for ALPHA3 are underway and we plan to initiate the trial in mid-2024.

Assuming favorable outcomes and subject to FDA discussions, we plan to seek FDA approval of cema-cel and ALLO-647 on the basis of the ALPHA3 trial.

Clinical Development Plan - Chronic Lymphocytic Leukemia (CLL)

We have initiated a new CLL cohort as part of our ALPHA2 trial.

This new cohort is a Phase 1b cohort that is a single-arm, open-label, multicenter study evaluating the safety and efficacy of cema-cel following lymphodepletion with fludarabine/cyclophosphamide and ALLO-647 in patients with R/R CLL/SLL.

This trial will include patients with high-risk CLL treated with ≥1 prior line of BTKi-based therapy or those treated with ≥2 prior lines of therapy, including a BTKi and BCL2i.

The primary endpoint of the phase 1b portion of this study is safety.

Secondary endpoints include overall response rate, duration of response, time to response, and progression-free survival per investigator assessment.

Up to approximately 40 patients may be enrolled in sites across the United States.

This study leverages currently active ALPHA2 trial sites in the U.S.

which should allow it to advance quickly.

We opened enrollment in the first quarter and anticipate initial data by year end 2024.

The ALPHA3 trial was initiated in 2024 and enrollment is currently ongoing with 40 sites activated in the United States.

Assuming favorable outcomes and subject to FDA discussions, we plan to seek FDA approval of cema-cel, and possibly ALLO-647, based on the ALPHA3 trial.

Additionally, assuming favorable outcomes, we anticipate that the ALPHA3 data set could be used to support EU regulatory approval.

The EMA has granted Marketing Authorizations for products, even when their clinical development programs did not involve any European sites.

These approvals are based on thorough evaluations of the products’ safety, efficacy, and quality.

This practice encompasses a wide range of indications and modalities, including those classified as Advanced Therapy Medicinal Products by the EMA.

Later this year, we plan to seek scientific advice from the EMA to assist us with finalizing our regulatory strategy for the EU and the UK.

Additionally, in February 2025, we entered into an Amended and Restated Strategic Collaboration Agreement with Foresight Diagnostics which expands our collaboration to enable the development of Foresight Diagnostics’ MRD assay as a companion diagnostic in the EU, UK, Canada and Australia in support of Allogene’s clinical development of cema-cel.

Anti-CD70 Oncology Development Program

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Patients who progress on immune checkpoint-based combination therapies can be treated with agents including cabozantinib, lenvatinib with everolimus, tivozanib, belzutifan or other therapies.

In October 2024, we announced that we received Regenerative Medicine Advanced Therapy (RMAT) designation for ALLO-316 for adult patients with advanced or metastatic RCC.

Results from the Phase 1 ALLO-316 TRAVERSE Trial

On April 17, 2023, we announced interim results from the Phase 1 TRAVERSE trial of ALLO-316 in patients with advanced or metastatic RCC who have progressed on or who are intolerant to standard therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.

On November 7, 2024, we announced interim results from the Phase 1 TRAVERSE trial of ALLO-316 in patients with advanced or metastatic RCC who have progressed on or who are intolerant to standard therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.

Data from dose escalation cohorts and the ongoing Phase 1b expansion cohort were included.

The Phase 1b expansion cohort is evaluating safety and efficacy of ALLO-316 at DL2 (80M CAR T cells) following a standard FC500 (fludarabine (30 mg/m2/day) and cyclophosphamide (500 mg/m2/d) for 3 days) lymphodepletion regimen.

The interim results provide proof-of-concept demonstrating the promise of an allogeneic CAR T product candidate to treat CD70-expressing RCC with ALLO-316.

As of the data extract date of March 23, 2023, in the ten patients with tumors known to express CD70, the disease control rate (DCR) was 100% including three patients who achieved a partial response (PR) (two confirmed and one unconfirmed, with the longest response lasting until month eight).

Cell expansion in patients with CD70 positive disease was robust and there was a trend toward greater tumor shrinkage in patients with high CD70 expression.

CD70+ Patients

Overall Response Rate (ORR), n (%)

Disease Control Rate (DCR), n (%)

Partial Response (PR), n (%)

There were 19 patients evaluable for safety, and the data demonstrated an adverse event profile generally consistent with autologous CAR T therapies.

One dose limiting toxicity of Grade 3 auto-immune hepatitis occurred in the second dose level.

Grade 3+ prolonged cytopenia was observed in three patients (18%).

CRS was all low grade with the exception of one case of Grade 3 CRS.

Neurotoxicity, which is now defined more broadly, was generally low grade and reversible with most events being fatigue or headache.

There were no cases of ICANs.

Infections occurred in eight patients of which four were Grade 3+ including one Grade 5 respiratory failure due to Covid-19 infection deemed unrelated to study treatment.

Grade 3+ prolonged cytopenia was observed in three patients (16%).

There were no cases of GvHD.

Infusion-Related Reaction

Neurotoxicity

Prolonged Gr3+ Cytopenia

As of the data extract date of October 14, 2024, 39 patients had been enrolled in the ongoing Phase 1 trial, of which 26 were confirmed to have CD70 positive RCC and were evaluable for efficacy outcomes.

Following a single infusion of ALLO-316 in heavily pretreated patients, the trial demonstrated best Overall Response Rate (ORR) of 50% and Confirmed Response Rate of 33% in those patients with CD70 Tumor Proportion Score (TPS) of ≥50% who received DL2.

Patients with a TPS of ≥50% comprise the majority of patients with advanced or metastatic RCC.

Of those with a TPS ≥50, 76% (16/21) experienced a reduction in tumor burden.

Two of six (33%) patients with high TPS who received the Phase 1b expansion regimen showed durable responses ongoing at ≥4 months.

Response Rates by CD70 Status and Dose

Patients Evaluable for Disease Outcomes a (N=34)

CD70 Positive (N=26) CD70 Negative or Unknown (N=8)

Best overall response, d n/N (%)

High TPS (≥50)

Low TPS (<50)

0/5 (0) 1/8 (13)

0/2 (0) 6/18 (33)

0/3 (0) 3/8 (38)

0/2 (0) 0/8 (0)

Confirmed ORR, e n/N (%)

High TPS (≥50)

Low TPS (<50)

0/5 (0) 1/8 (13)

0/2 (0) 4/18 (22)

0/3 (0) 2/8 (25)

0/2 (0) 0/8 (0)

a Patients evaluable for disease outcome includes those who received ALLO-316 and had at least one tumor assessment.

b Standard fludarabine and cyclophosphamide plus ALLO-647

c Includes FC300 and FC500

d Best overall response across visits did not require confirmation for CR/PR.

e Confirmed overall response of CR/PR required confirmation at the subsequent visit.

Regarding safety data, the most common all-grade adverse events were CRS (with only one grade ≥3), fatigue (59%), neutropenia (56%), decreased white blood cell count (54%), anemia (51%) and nausea (51%).

ICANS was minimal at 8% and no GvHD occurred.

Most Prevalent Treatment-Emergent Adverse Events (TEAEs) (>40% Any Grade Incidence) and

Adverse Events of Special Interest (AESI)

Adverse Event, n(%)

All Patients (N=39)

DL2 FC500 (N=11)

White blood cell count decreased

Thrombocytopenia

AEs of Special Interest

Viral infections

Neurotoxicity c

Graft-versus-host disease

a TEAE included all AEs that started from the first dose date of study drug in each treatment period up to start of another treatment period, death, or the date prior to initiation of another anti-cancer agent, whichever occurred first.

b Infection events (62%) were primarily low grade;

the most common was viral infections (33%) with cytomegalovirus infection and COVID-19 (any grade, 18% and 15%;

Grade ≥3, 0% and 5%, respectively).

c Neurotoxicity includes system organ class of nerve system disorders and psychiatric disorders with onset date up to Study Day 30 post ALLO-316 infusion.

d IEC-HS includes the preferred terms IEC-HS, HLH, Hemophagocytic lymphohistiocytosis, and atypical HLH.

Two patients developed an inflammatory syndrome prior to the existence of IEC-HS as a term in MedDRA, which has been updated as of September 2023.

Two dose-limiting toxicity (DLT) events of autoimmune hepatitis and cardiogenic shock were reported.

Each event occurred in two separate participants who received FCA (FC300 plus ALLO-647) lymphodepletion and DL2 of ALLO-316.

Three Grade 5 treatment-related adverse events were reported:

1) cardiogenic shock, which was one of the two DLT events;

2) sepsis from multi-drug resistant Klebsiella pneumoniae in a participant who received DL4 of ALLO-316.

This participant had a prior episode of muscle abscess and bacteremia from the same multi-drug resistant Klebsiella and was receiving anakinra and dexamethasone for hyperinflammation;

3) failure to thrive in a participant 16 months after treatment with ALLO-316.

This subject had tumor response of stable disease (SD) at month 12 and no interval scans to evaluate disease status prior to death.

Clinical Development Plan

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The trial is now deploying the IVD assay for the purposes of identifying patients most likely to benefit from ALLO-316.

TRAVERSE will continue to explore varying cell dose and lymphodepletion regimens in CD70 positive RCC patients.

During the advancement of the TRAVERSE trial with ALLO-316, we have observed allogeneic CAR T cell expansion and persistence driven by CD70 CAR that allows elimination of alloreactive host lymphocytes.

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This algorithm may mitigate the treatment-associated hyperinflammatory response without compromising the CAR T function needed to eradicate solid tumors.

We have recently implemented a protocol amendment to further maximize the benefit-risk of ALLO-316 in patients with CD70+ RCC.

The next update from this trial is planned for a medical forum in second quarter 2024 and will discuss the safety algorithm that is believed to be an important advance for the TRAVERSE trial.

A more robust data update from the ongoing trial with the updated protocol is planned for later in 2024.

Enrollment in the Phase 1b cohort has been completed and we are now pausing further standard dosing pending durability results for the enrolled patients.

Additional data from the Phase 1b expansion cohort is expected to be announced in mid-2025.

Anti-CD19/CD70 Autoimmune Disease Development Program

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The anti-rejection features of ALLO-329 may help reduce or eliminate the need for lymphodepletion prior to treatment with ALLO-329.

Lead Target Indications:

Systemic Lupus Erythematosus (SLE),

Lupus Nephritis, Idiopathic Inflammatory Myopathies, and Systemic Sclerosis

In January 2025 we announced that the FDA has cleared our IND for a rheumatology basket study of ALLO-329.

Our RESOLUTION trial will evaluate the safety and efficacy of ALLO-329 across multiple autoimmune diseases, including systemic lupus erythematosus (SLE) (including lupus nephritis), idiopathic inflammatory myopathies, and systemic sclerosis.

SLE is a chronic, systemic autoimmune disease where the body's immune system mistakenly attacks its own tissues, and is characterized by immune dysregulation, autoantibody production, and inflammation affecting multiple organs.

Lupus nephritis (LN) is a serious renal complication of SLE.

In LN, the immune system targets the kidneys, leading to inflammation, glomerular damage, and potential renal failure.

Idiopathic inflammatory myopathies (IIMs) are a group of rare autoimmune diseases characterized by chronic muscle inflammation and progressive weakness, mainly affecting proximal skeletal muscles.

Systemic sclerosis (SSc) is a chronic autoimmune connective tissue disorder characterized by vascular dysfunction, immune dysregulation, and progressive fibrosis affecting the skin and internal organs (lungs, heart, kidneys, and gastrointestinal tract).

Approximately 330,000 cases of SLE (according to Decision Resources Group), 70,000 cases of IIM (according to The Myositis Association), and 100,000 cases of SSc (according to Bergamasco et al, Dove Medical Pres Limited) are estimated to be diagnosed in the United States.

These autoimmune diseases generally require targeted immunosuppressive and symptom-specific treatments.

SLE is primarily managed with hydroxychloroquine and NSAIDs for mild cases, while severe disease, such as lupus nephritis, necessitates immunosuppressants like mycophenolate mofetil or cyclophosphamide, with biologics such as belimumab and anifrolumab for refractory cases.

IIM (including polymyositis and dermatomyositis) is typically treated with high-dose corticosteroids, often combined with methotrexate or azathioprine, while severe or refractory cases may require IVIG or rituximab.

SSc management focuses on symptom control, with calcium channel blockers for Raynaud’s phenomenon, mycophenolate mofetil for interstitial lung disease, and vasodilators like sildenafil or bosentan for pulmonary arterial hypertension.

Current treatments for SLE, IIM, and SSc have significant limitations, including broad immunosuppression, long-term toxicity, delayed onset of action, disease progression despite therapy, frequent dosing and refractory cases.

Clinical Development Plan

We are developing ALLO-329, an allogeneic CAR T cell product candidate targeting both CD19 and CD70 for the treatment of certain autoimmune diseases.

Inclusion of an anti-CD70 CAR in ALLO-329 is designed to reduce or eliminate the need for standard chemotherapy by preventing premature rejection while also targeting CD70+ activated lymphocytes, which may play a direct role in AID pathogenesis.

Initiation of this Phase 1 trial with ALLO-329 is expected in early 2025.

Following the clearance of an IND in January 2025, we plan to initiate a Phase 1 clinical trial (the RESOLUTION trial) of ALLO-329 in adult patients with systemic lupus erythematosus (including lupus nephritis), idiopathic inflammatory myopathies, and systemic sclerosis in mid-2025.

Future Opportunities

Currently, we remain focused on our four key programs described above.

Currently, we remain focused on our three key programs described above.

As we advance those programs, we may seek to utilize our allogeneic platform to pursue additional targets of interest, particularly through strategic partnerships.

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This work is performed in our process development environment to evaluate and assess variability in each step of the process in order to define the most reliable production conditions.

Historically, we have used a CDMO to manufacture our cell-based product candidates in the United States, and we managed all other aspects of the supply, including planning, CDMO oversight, disposition and distribution logistics.

The CDMO is subject to cGMP requirements, using qualified equipment and materials.

We also have utilized separate third-party contractors to manufacture cGMP raw materials that are used for the manufacturing of our product candidates, such as viral vectors that are used to deliver the applicable CAR gene into the T cells.

We are currently utilizing Cell Forge 1 (CF1) our state-of-the-art cell therapy manufacturing facility in Newark, California to manufacture our product candidates.

We also utilize separate third-party contractors to manufacture cGMP raw materials that are used for the manufacturing of our product candidates, such as viral vectors that are used to deliver the applicable CAR gene into the T cells.

We believe all materials and components utilized in the production of the cell line, viral vector and final T cell product are available from qualified suppliers and suitable for pivotal process development in readiness for registration and commercialization.

In February 2019, we entered into a lease for approximately 118,000 square feet to develop a state-of-the-art cell therapy manufacturing facility in Newark, California that we call Cell Forge 1 (CF1).

We completed the intended build-out of the majority of the facility at the end of 2020.

We are currently utilizing CF1 for clinical manufacturing of our product candidates.

We continue to rely upon certain third-party contractors to manufacture cGMP raw materials.

Introducing product manufactured at CF1 into an ongoing clinical trial will require that we meet certain regulatory conditions, such as establishing comparability with the product candidates manufactured at our CDMO, and our inability to meet such conditions would result in investment of additional resources and delay of our clinical trial timeline.

Although we are utilizing CF1 for clinical manufacturing, we may continue to rely on CDMOs and other third parties for the manufacturing and processing of our product candidates in the future.

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Strategic Agreements

On December 14, 2020, we entered into a License Agreement with Allogene Overland Biopharm (CY) Limited (Allogene Overland), a joint venture established by us and Overland Pharmaceuticals (CY) Inc., pursuant to a Share Purchase Agreement, dated December 14, 2020, for the purpose of developing, manufacturing and commercializing allogeneic CAR T cell therapies for patients in greater China, Taiwan, South Korea and Singapore.

Allogene Overland Biopharm (CY) Limited (Allogene Overland), later renamed Overland Therapeutics Inc.

(Overland Therapeutics), was initially established as a joint venture by us and Overland Pharmaceuticals (CY) Inc.

(Overland) pursuant to a Share Purchase Agreement (Share Purchase Agreement), dated December 14, 2020.

Concurrently, on December 14, 2020, we entered into a License Agreement (License Agreement) with Allogene Overland for the purpose of developing, manufacturing and commercializing certain allogeneic CAR T cell therapies (JV Licensed Products) for patients in greater China, Taiwan, South Korea and Singapore (the JV Territory).

On May 24, 2024, we, Overland, and Allogene Overland entered into a Share Exchange Agreement (Share Exchange Agreement) pursuant to which Overland’s cell therapy business merged into Allogene Overland (the Organizational Restructuring).

Under a separate agreement between Overland and HH BioPharma Holdings Ltd.

(HBP) executed on May 24, 2024, Overland distributed all Series Seed Preferred Shares of Allogene Overland held by Overland to HBP and HBP has assumed all rights and obligations attached to such shares and all rights and obligations of Overland under the Share Exchange Agreement.

In connection with the Organizational Restructuring, on May 24, 2024, we and Allogene Overland PRC, entered into a First Amendment to the License Agreement (the License Amendment) to amend and supplement certain provisions of the License Agreement.

Under the License Amendment, we continue to grant Allogene Overland PRC an exclusive license to develop, manufacture, and commercialize the JV Licensed Products in the JV Territory, with us retaining exclusive rights to the JV Licensed Products outside the JV Territory

We have also entered into multiple additional strategic agreements and collaborations, including an Asset Contribution Agreement with Pfizer (the Pfizer Agreement), a License Agreement with Cellectis (the Cellectis Agreement), the Servier Agreement, a Collaboration and License Agreement (the Notch Agreement) with Notch Therapeutics Inc.

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These licensed assets include rights to the Cellectis TALEN ® gene-editing technology to engineer T cells that lack functional TCRs and to inactivate the CD52 gene in donor cells.

We have exclusive worldwide rights to these patents for

certain antigen targets, including BCMA, CD70, FLT3, DLL3 and Claudin 18.2, and have U.S.

rights to these patents for CD19.

We also have rights to a Cellectis U.S.

patent for technology covering an engineered T cell therapy combining CD52 gene knockout in combination with an anti-CD52 antibody for certain products directed against certain antigen targets.

For our lead programs, our patent rights are generally composed of patents and pending patent applications that are solely owned by us, co-owned with Servier, co-owned with Cellectis, exclusively licensed from Pfizer, exclusively licensed from Servier, or exclusively licensed from Cellectis.

Our patent portfolio includes protection for our clinical-stage product candidates, ALLO-501, cema-cel, ALLO-715, ALLO-605 and ALLO-316, as well as our research-stage candidates.

We have exclusive worldwide rights to these patents for certain antigen targets, including BCMA, CD70, FLT3, DLL3 and Claudin 18.2, and have U.S., EU, and UK rights to these patents for CD19.

We also have rights to Cellectis intellectual property for technology covering an engineered T cell therapy combining CD52 gene knockout in combination with an anti-CD52 antibody for certain products directed against certain antigen targets.

For our lead programs, our patent rights are generally composed of patents and pending patent applications that are solely owned by us, co-owned with Servier, co-owned with Cellectis, co-owned with Pfizer, exclusively licensed from Pfizer, exclusively licensed from Servier, or exclusively licensed from Cellectis.

Our patent portfolio includes protection for our clinical-stage product candidates, ALLO-501, cema-cel, ALLO-316, ALLO-329, ALLO-715, and ALLO-605, as well as our research-stage candidates.

With respect to ALLO-501 and cema-cel, we have an exclusive license from Servier to patent rights in the United States covering compositions of matter of and methods of making and using ALLO-501 and cema-cel.

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In August 2017, Novartis obtained FDA approval to commercialize Kymriah® for the treatment of children and young adults with B-cell ALL that is refractory or has relapsed at least twice.

In May 2018, Kymriah® received FDA approval for adults with certain types of LBCL who have not responded to, or who have relapsed after, at least two other types of systemic treatment (3rd-line LBCL), and in May 2022, Kymriah® received FDA approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy.

In October 2017, Kite/Gilead obtained FDA approval to commercialize Yescarta®, for the treatment of adult patients with 3rd-line LBCL.

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In February 2021, BMS obtained FDA approval for its anti-CD19 autologous T cell therapy, Breyanzi® for the treatment of adults with 3rd-line LBCL.

The label of Breyanzi® label was extended to 2 nd -line LBCL in June 2022.

The label of Breyanzi® label was extended to 2nd-line LBCL in June 2022, R/R Chronic Lymphocytic Leukemia (CLL) in March 2024, R/R FL in May 2024, and R/R Mantle Cell Lymphoma (MCL) in May 2024.

Autologous cell therapies directed at BCMA have been commercialized by BMS and Jannsen, a Johnson & Johnson company.

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Jannsen and partner Legend Bio received approval for Carvykti®, an anti-BCMA autologous T cell therapy, for the same indication in February 2022.

Both Abecma® and Carvykti® have succeeded in pivotal trials in earlier lines of R/R myeloma and are expected to gain label extensions into this market.

Autologous T cell therapies are being developed by a number of additional companies, including but not limited to 2seventy bio, Inc., Adaptimmune Therapeutics PLC, Alaunos Therapeutics, Inc., Arcellx, Inc., Arsenal Biosciences, Inc., Autolus Therapeutics plc, CARGO Therapeutics, Inc.

Eureka Therapeutics, Inc., Galapagos NV, Gilead Sciences, Inc., Gracell Biotechnologies, Inc., ImmPACT Bio, USA Inc., Instil Bio, Inc., Iovance Biotherapeutics, Inc., Legend Biotech Corp., Mustang Bio, Inc., Novartis International AG, Triumvira Immunologics, and TScan Therapeutics, Inc.

Both Abecma® and Carvykti® have succeeded in pivotal trials in earlier lines of R/R myeloma and have gained label extensions into this market in 2024.

Eureka Therapeutics, Inc., Galapagos NV, Gilead Sciences, Inc., ImmPACT Bio, USA Inc., Instil Bio, Inc., Iovance Biotherapeutics, Inc., Legend Biotech Corp., Lyell Immunopharma Inc., Mustang Bio, Inc., Triumvira Immunologics, and TScan Therapeutics, Inc.

Autologous CAR T therapy has made significant advances in addressing R/R NHL, and has moved to earlier lines of therapy, as further described above.

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Allogeneic T cell products have yet to receive FDA approval though the number of companies developing allogeneic product candidates is substantial.

These include AstraZeneca, plc, Atara Biotherapeutics, Inc., Beam Therapeutics, Inc., Caribou Biosciences, Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., Fate Therapeutics, Inc., Gilead Sciences, Inc., Imugene Ltd., Intellia Therapeutics, Inc., Legend Biotech Corp., Poseida Therapeutics, Inc., Precision Biosciences, Inc., and Sana Biotechnology, Inc.

These include AstraZeneca, plc, Atara Biotherapeutics, Inc., Beam Therapeutics, Inc., Caribou Biosciences, Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., F.

Hoffmann-La Roche AG, Fate Therapeutics, Inc., Gilead Sciences, Inc., Imugene Ltd., Intellia Therapeutics, Inc., Legend Biotech Corp., Precision Biosciences, Inc., and Sana Biotechnology, Inc.

Some of the allogeneic T cell candidates under development target the same antigens that are part of our clinical pipeline, such as CD19, BCMA and CD70.

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For instance, we may experience competition from companies, such as AbbVie, Inc., Amgen Inc., BMS, Compass Therapeutics, Inc., F.

Hoffmann-La Roche AG, Genmab A/S, GlaxoSmithKline plc, Harpoon Therapeutics, Inc., Immunocore Holdings plc, Johnson & Johnson, MacroGenics, Inc., Merus N.V., Pfizer, Regeneron Pharmaceuticals, Inc., and Xencor Inc., that are pursuing bispecific T cell engagers that target both the cancer antigen and T cell receptor, thus bringing both cancer cells and T cells in close proximity to maximize the likelihood of an immune response to the cancer cells.

Hoffmann-La Roche

AG, Genmab A/S, GlaxoSmithKline plc, Immunocore Holdings plc, Johnson & Johnson, MacroGenics, Inc., Merck & Co.

Inc., Merus N.V., Pfizer, Regeneron Pharmaceuticals, Inc., and Xencor Inc., that are pursuing bispecific T cell engagers that target both the cancer antigen and T cell receptor, thus bringing both cancer cells and T cells in close proximity to maximize the likelihood of an immune response to the cancer cells.

Multiple bi-specific T cell engagers targeting BCMA for myeloma and CD20 for lymphoma are advancing rapidly in development and the first products in each category gained FDA approval in 2022.

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In addition to the significant competition noted above in oncology markets, as early data in the use of CAR T cell therapy for the treatment of autoimmune disease has been emerging since 2022, there have been many companies initiating autologous and/or allogeneic cell therapy development programs that would be in direct competition to our autoimmune program.

For example, we may experience competition in these markets from companies such as Adicet Bio, Inc., Atara Biotherapeutics, Inc., Autolus Therapeutics plc, BMS, Cabaletta Bio, Inc., Cartesian Therapeutics, Inc., CRISPR Therapeutics AG, Fate Therapeutics, Inc., Gracell Biotechnologies, Inc., ImmPACT Bio USA, Inc., Kyverna Therapeutics, Inc., Nkarta, Inc., Novartis, and Sana Biotechology, Inc.

For example, we may experience competition in these markets from companies such as Adicet Bio, Inc., Arcellx, Inc., Atara Biotherapeutics, Inc., Autolus Therapeutics plc, BMS, Cabaletta Bio, Inc., Caribou Biosciences, Inc., Cartesian Therapeutics, Inc., CRISPR Therapeutics AG, Fate Therapeutics, Inc., Gracell Biotechnologies, Inc., ImmPACT Bio USA, Inc., Kyverna Therapeutics, Inc., Nkarta, Inc., Novartis, Sana Biotechology, Inc., and TG Therapeutics Inc.

Many of our competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, pre-clinical testing, clinical trials, manufacturing, and marketing than we do.

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Failure to comply with the applicable U.S.

requirements at any time during the product development process, approval process or after approval, may subject an applicant to administrative or judicial sanctions.

requirements at any time during the product development process, approval process or after approval, may subject an applicant to

administrative or judicial sanctions.

FDA sanctions could include, among other actions, refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls or withdrawals from the market, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties.

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Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, if at all.

The FDA or the sponsor or its data safety monitoring board may suspend or terminate a clinical trial at any time on various

grounds, including a finding that the research patients are being exposed to an unacceptable health risk, including risks inferred from other unrelated immunotherapy trials.

The FDA or the sponsor or its data safety monitoring board may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research patients are being exposed to an unacceptable health risk, including risks inferred from other unrelated immunotherapy trials.

Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the biological product has been associated with unexpected serious harm to patients.

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Once the submission is accepted for filing, the FDA begins an in-depth substantive review of the BLA.

The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, potent, and/or effective for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity.

preserve the product’s identity, safety, strength, quality, potency and purity.

The FDA may refer applications for novel biological products or biological products that present difficult questions of safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a recommendation as to whether the application should be approved and under what conditions.

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The orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review or approval process.

If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.

Orphan drug exclusivity does not prevent FDA from approving a different drug or biologic for the same disease or condition, or the same drug or biologic for a different disease or condition.

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In addition, exclusive marketing rights in the United States may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition.

The FDA granted orphan drug designation to ALLO-715 and ALLO-605 for the treatment of multiple myeloma.

Expedited Development and Review Programs

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Unique to a fast track product, the FDA may consider for review sections of the BLA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the BLA, the FDA agrees to accept sections of the BLA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the BLA.

Any product submitted to the FDA for approval, including a product with a fast track designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated

A product is eligible for priority review if it has the potential to provide safe and effective therapy where no satisfactory alternative therapy exists or a significant improvement in the treatment, diagnosis or prevention of a disease compared to marketed products.

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Fast track designation, priority review, RMAT and Breakthrough therapy designation do not change the standards for approval but may expedite the development or approval process.

We have received RMAT designation for ALLO-715 and cema-cel in r/r multiple myeloma and r/r LBCL, respectively, and fast track designation for cema-cel, ALLO-605, ALLO-316 and ALLO-647.

Post-Approval Requirements

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cGMP regulations require among other things, quality control and quality assurance as well as the corresponding maintenance of records and documentation and the obligation to investigate and correct any deviations from cGMP.

Manufacturers and other entities involved in the manufacture and distribution of approved products are required to register their establishments with the FDA and certain state agencies, and are

subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws.

Manufacturers and other entities involved in the manufacture and distribution of approved products are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP and other laws.

Accordingly, manufacturers must continue to expend time, money, and effort in the area of production and quality control to maintain cGMP compliance.

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Under the FDCA, in vitro diagnostics, including companion diagnostics, are regulated as medical devices.

In the U.S., the FDCA and its implementing regulations, and other federal and state statutes and regulations govern, among other

things, medical device design and development, preclinical and clinical testing, premarket clearance or approval, registration and listing, manufacturing, labeling, storage, advertising and promotion, sales and distribution, export and import, and post-market surveillance.

In the U.S., the FDCA and its implementing regulations, and other federal and state statutes and regulations govern, among other things, medical device design and development, preclinical and clinical testing, premarket clearance or approval, registration and listing, manufacturing, labeling, storage, advertising and promotion, sales and distribution, export and import, and post-market surveillance.

Unless an exemption applies, medical devices, including companion diagnostic tests, require marketing clearance or approval from the FDA prior to commercial distribution.

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Approval of a PMA is not guaranteed, and the FDA may ultimately respond to a PMA submission with a not approvable determination based on deficiencies in the application and require additional clinical trial or other data that may be expensive and time-consuming to generate and that can substantially delay approval.

If the FDA’s evaluation of the PMA application is favorable, the FDA typically issues an approvable letter requiring the applicant’s agreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to secure final approval of the PMA.

secure final approval of the PMA.

If the FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not approvable letter.

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As a result of a modification made by the Fraud Enforcement and Recovery Act of 2009, a claim includes “any request or demand” for money or property presented to the U.S.

For example, pharmaceutical and other healthcare companies have been, and continue to be, investigated or prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product and for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-reimbursable, uses.

For example, pharmaceutical and other healthcare companies have

been, and continue to be, investigated or prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product and for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-reimbursable, uses.

HIPAA created additional federal criminal statutes that prohibit knowingly and willfully executing, or attempting to execute, a scheme to defraud or to obtain, by means of false or fraudulent pretenses, representations or promises, any money or property owned by, or under the control or custody of, any healthcare benefit program, including private third-party payors and knowingly and willfully falsifying, concealing or covering up by trick, scheme or device, a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.

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Among other things, HITECH makes HIPAA’s privacy and security standards directly applicable to business associates that are independent contractors or agents of covered entities that receive or obtain protected health information in connection with providing a service on behalf of a covered entity as well as their covered subcontractors.

HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general

new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

HITECH also created four new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions.

In addition, state laws govern the privacy and security of health information in specified circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.

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In the United States and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend, in part, on the extent to which third-party payors provide coverage, and establish adequate reimbursement levels for such products.

In the United States, third-party payors include federal and state healthcare programs, private managed care providers, health insurers and other organizations.

In the United States, third-party payors include federal and state

healthcare programs, private managed care providers, health insurers and other organizations.

The process for determining whether a third-party payor will provide coverage for a product may be separate from the process for setting the price of a product or for establishing the reimbursement rate that such a payor will pay for the product.

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The downward pressure on health care costs has become very intense.

increasingly high barriers are being erected to the entry of new products.

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

In addition, in some countries, cross-border imports from low-priced markets exert a commercial pressure on pricing within a country.

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For example, the Affordable Care Act has substantially changed healthcare financing and delivery by both governmental and private insurers.

The ACA, among other things, increased the minimum level of Medicaid rebates payable by manufacturers of brand name drugs;

required collection of rebates for drugs paid by Medicaid managed care organizations;

required manufacturers to participate in a coverage gap discount program, under which they must agree to offer point-of-sale discounts (increased to 70 percent, effective as of January 1, 2019) off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;

imposed a non-deductible annual fee on pharmaceutical manufacturers or importers who sell certain “branded prescription drugs” to specified federal government programs, implemented a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected expanded the types of entities eligible for the 340B drug discount program;

expanded eligibility criteria for Medicaid programs;

created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research;

and established a Center for Medicare Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

There have been legal and political challenges to certain aspects of the Affordable Care Act.

For example, President Trump signed several executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the Affordable Care Act.

In December 2017, Congress repealed the tax penalty for an individual’s failure to maintain Affordable Care Act-mandated health insurance, commonly known as the “individual mandate”, as part of legislation enacted in 2017, informally titled the Tax Cuts and Jobs Act of 2017 (Tax Act).

In addition, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the Affordable Care Act’s mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminated the health insurer tax.

On June 17, 2021, the U.S.

Supreme Court dismissed a challenge on procedural grounds that argue the Affordable Care Act is unconstitutional in its entirety because the "individual mandate" was repealed by Congress.

In addition, there have been a number of health reform initiatives that have impacted the Affordable Care Act.

For example, the Bipartisan Budget Act of 2018 (BBA), among other things, amended the Affordable Care Act, effective January 1, 2019, to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole”.

In December 2018, CMS published a final rule permitting further collections and payments to and from certain Affordable Care Act qualified health plans and health insurance issuers under the Affordable Care Act risk adjustment program in response to the outcome of federal district court litigation regarding the method CMS uses to determine this risk adjustment.

On August 16, 2022, President Biden signed the Inflation Reduction Act of 2022 (IRA) into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in Affordable Care Act marketplaces through plan year 2025.

There have been legal and political challenges and amendments to certain aspects of the Affordable Care Act.

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 Affordable Care Act 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.

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Other legislative changes have been proposed and adopted since the Affordable Care Act was enacted.

For example, in August 2011, President Obama signed into law the Budget Control Act of 2011, which, among other things, created the Joint Select Committee on Deficit Reduction to recommend to Congress proposals in spending reductions.

The Joint Select

Committee on Deficit Reduction did not achieve a targeted deficit reduction of at least $1.2 trillion for fiscal years 2012 through 2021, triggering the legislation’s automatic reduction to several government programs.

For example, in August 2011, the Budget Control Act of 2011 was signed into law, which, among other things, created the Joint Select Committee on Deficit Reduction to recommend to Congress proposals in spending reductions.

The Joint Select Committee on Deficit Reduction did not achieve a targeted deficit reduction of at least $1.2 trillion for fiscal years 2012 through 2021, triggering the legislation’s automatic reduction to several government programs.

This includes aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect beginning on April 1, 2013 and will stay in effect until 2032 unless additional Congressional action is taken.

Additionally, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.

In January 2013, the American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.

Additionally, on March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024.

Additionally, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.

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Congressional inquiries and federal and state legislative activity designed to, among other things, bring more transparency to drug pricing, reduce the cost of prescription drugs under Medicare, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs.

At the federal level, the Trump administration used several means to propose or implement drug pricing reform, including through federal budget proposals, executive orders and policy initiatives.

In addition, in July 2021, the Biden administration released an executive order, “Promoting Competition in the American Economy,” with multiple provisions aimed at prescription drugs.

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

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

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

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

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

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

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

For example, the IRA, among other things (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 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 in fiscal year 2023.

On August 15, 2024, HHS announced the agreed-upon price 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.

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

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

The current administration is pursuing policies to reduce regulations and expenditures across government including at HHS, the FDA, the Centers for Medicare & Medicaid Services (“CMS”) and related agencies.

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

These actions may, for example, include directives to reduce agency workforce, rescinding a previous executive order tasking the Center for Medicare and Medicaid Innovation (“CMMI”) to consider new payment and healthcare models to limit drug spending and eliminating a previous 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.

Individual states in the United States have also become increasingly active in passing legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

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Privacy Laws and Regulations

In the ordinary course of our business, we may process personal or sensitive data.

Accordingly, we are, or may become, subject to numerous data privacy and security obligations, including federal, state, local, and foreign laws, regulations, guidance, and industry standards related to data privacy, security, and protection.

In the ordinary course of our business, we and the third parties with whom we work process personal and sensitive data.

Accordingly, we are, and may in the future become, subject to numerous data privacy and security obligations, including federal, state, local, and foreign laws, regulations, guidance, and industry standards related to data privacy, security, and protection.

For example, in addition to EU regulations related to the approval and commercialization of our products, our activities in the EU subject us to the EU’s General Data Protection Regulation (EU GDPR).

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For example, the California Consumer Privacy Act (CCPA) creates new individual privacy rights for consumers (as that word is broadly defined in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households.

The CCPA requires covered companies to provide new disclosures to California consumers, affords California residents certain rights related to their personal data, including the right to opt-out of certain sales of personal data, and allows for a new cause of action for certain data breaches.

In addition, the California Privacy Rights Act of 2020 (CPRA), effective January 1, 2023, expanded the CCPA by, among other things, giving California residents the ability to limit use of certain sensitive personal data, establishing restrictions on personal data retention, expanding the types of data breaches that are subject to the CCPA’s private right of action, and establishing a new California Privacy Protection Agency to implement and enforce the CCPA.

As our business progresses, the CCPA and the CPRA may become applicable and impact (possibly significantly) our business activities and exemplifies the vulnerability of our business to the evolving regulatory environment related to personal data and protected health information.

Many other US states—including Virginia, Connecticut, Utah, and Colorado—have passed similar comprehensive privacy laws, and more are likely to do so in the future.

The CCPA provides for fines and allows private litigants affected by certain data breaches to recover significant statutory damages.

As our business progresses, the CCPA may become applicable and impact (possibly significantly) our business activities and exemplifies the vulnerability of our business to the evolving regulatory environment related to personal data and protected health information.

Many other US states have passed similar comprehensive privacy laws, and more are likely to do so in the future.

See the section titled “Risk Factors – Risks Related to Our Business and Industry” and “Risk Factors – Risks Related to Government Regulation” for additional information about the laws and regulations to which we may become subject and about the risks to our business associated with such laws and regulations.

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We believe our workforce is key to Allogene’s success and we actively focus on the following core elements of human capital:

(1) our “One Allogene” culture, (2) diversity, equity, inclusion and belonging, and (3) recruitment, development and retention.

(1) our “One Allogene” culture, (2) belonging, fairness and representation and (3) recruitment, development and retention.

We have also strived to create a safe working environment and have increased onsite presence since the end of the pandemic.

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We accomplish more together than as individuals when we unite as one Allogene community.

We are resilient, because we strive to save the lives of people with cancer.

We are resilient, because we strive to save the lives of people with cancer and improve the lives of people with autoimmune disorders.

We come together with purpose, courage and flexibility despite challenges or uncertainty because every potential patient is someone’s partner, parent, child, sibling or friend.

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We are good to one another.

We value diversity of thought, background and expertise, we earn each other’s trust, and assume good intention as we collaborate to help patients.

We value distinct perspectives, backgrounds and expertise, we earn each other’s trust, and assume good intention as we collaborate to help patients.

We are creating a scientific revolution.

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In addition, our core values of collaboration, leadership, innovation and focus help drive our culture and behaviors and are layered into our performance reviews so that we can keep ourselves and our employees accountable.

Diversity, Equity, Inclusion and Belonging

We are committed to cultivating, fostering, and preserving a culture of diversity, equity, inclusion and belonging (DEIB).

We foster an inclusive environment through respect, collaboration, and open communication.

We embrace and encourage differences in age, color, disability, ethnicity, family or marital status, gender identity or expression, language, national origin, culture or customs, physical and mental ability, political affiliation, race, religion, sexual orientation, socio-economic status, veteran status, and other characteristics that make our employees unique.

We also embrace differences in experience and background, and welcome diversity of opinions and thought when making decisions.

As of March 1, 2024, our employees were self-reportedly 51% women.

Of our Director-level and above employees, 47% were self-reportedly women.

In addition, as of March 1, 2024, 67% of all employees were self-reportedly ethnic or racial minorities in the U.S., with 49% Asian, 2% Black or African American, 8% Hispanic or Latino and 8% of other minority groups or two or more races.

Of our Director-level and above employees, 48% were self-reportedly ethnic or racial minorities in the U.S., with 31% Asian, 5% Black or African American, 4% Hispanic or Latino and 8% of other minority groups or two or more races.

Although we are proud of our efforts to attract the best talent from the broadest pool of talent, we continue to focus on broadening our outreach to underrepresented groups by posting our open positions on top job boards to seek diverse, qualified candidates.

We have and will continue to conduct unconscious bias training for interviewers and hiring managers.

Our recruiters and hiring managers have active talent recruitment strategies, including the use of diverse slates.

Our DEIB initiatives are applicable to our practices and policies, such as those on recruitment, compensation and professional development.

We are also progressing the ongoing development of an inclusive work environment grounded in psychological safety that encourages:

Belonging, Fairness and Representation

We are committed to cultivating, fostering, and preserving a culture of belonging, fairness and representation where we foster a supportive, empowering and positive environment through respect, collaboration, and open communication.

We embrace and encourage differences across all demographics that make our employees unique.

We also embrace differences in experience and background, and welcome different opinions and unique perspectives when making decisions.

We believe that in cultivating this environment, our staff feel that they are able to contribute to their full potential.

As of March 1, 2025, the general demographic makeup of our workforce remains generally consistent with past years.

We are proud of our efforts to attract the best talent from the broadest pool of talent and we continue to focus on broadening our outreach to extend to all groups by posting our open positions on a variety of top job boards to seek a wide range of qualified candidates.

We have and will continue to conduct training for interviewers and hiring managers to ensure they are making decisions based solely on facts, not assumptions, or irrelevant information.

Our recruiters and hiring managers have active talent recruitment strategies to ensure that we are reaching the best talent available and giving qualified job applicants the opportunity to compete for positions.

Our initiatives embrace and complement our One Allogene culture by ensuring that our Company and its employees are taking responsibility for ensuring a supportive, empowering and positive work environment where employees feel valued, engaged and fully committed to our mission to serve patients.

These initiatives are applicable to our practices and policies, such as those on recruitment, compensation and professional development.

We are also progressing the ongoing development of an supportive work environment grounded in psychological safety that encourages:

• Respectful communication and cooperation between all employees.

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• Teamwork and employee participation, permitting the representation of employee perspectives.

• Employer and employee contributions to the communities we serve to promote a greater understanding and respect for diversity and inclusion.

To champion our efforts in this area, we established a governance structure and formed a DEIB Committee which is comprised of employees of various levels, departments and backgrounds.

The DEIB Committee formalized a DEIB mission statement and also advanced a DEIB policy that sets forth our commitment to the importance of DEIB and the responsibility of our employees to adhere to our policy, including by treating others with dignity and respect at all times.

Pursuant to our DEIB policy, all employees are also encouraged to attend and complete annual diversity awareness training to enhance their knowledge to fulfill this responsibility.

The DEIB Committee continually works to respond to feedback provided by peers, and present suggestions on our practices and policies to encourage and enforce an environment in which all employees feel included and empowered to achieve their best.

• Employer and employee contributions to the communities we serve to promote a greater understanding and respect for others.

To champion our efforts in this area, we established a governance structure and formed a cross-functional committee (Committee) comprised of employees of various levels, departments and backgrounds to help advance and promote our commitment to maintaining the culture described above, and the responsibility of our employees to treat others with dignity and respect at all times regardless of our differences.

All employees are also encouraged to attend and complete annual awareness training to enhance their knowledge to fulfill this responsibility.

The Committee continually works to respond to feedback provided by peers, and present suggestions on our practices and policies to encourage and enforce an environment in which all employees feel that they are part of our team and empowered to achieve their best.

We believe in equal pay for equal work.

We establish components and ranges of compensation based on market and benchmark data.

Within this context, we strive to pay all employees equitably within a reasonable range, taking into consideration factors such as role;

internal equity;

Within this context, we strive to pay all employees fairly within a reasonable range, taking into consideration factors such as role;

internal consistency;

job location;

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We also regularly review our compensation practices and analyze our compensation decisions for individual employees and our workforce as a whole on at least an annual basis.

Since 2020, we have conducted a pay equity analysis which we believe demonstrates that our compensation practices and structure are equitable.

We plan to continue to seek feedback from the DEIB Committee, and all our employees to help us achieve our full potential.

Since 2020, we have conducted a pay analysis annually which we believe demonstrates that our compensation practices and structure are fair.

Recruitment, Development and Retention

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Learning and development, training and other resources are an integral part of retaining our employees and creating a culture of learning and leadership within Allogene.

For instance, we have an annual required manager training that allows managers to learn and practice fundamental management skills to enable them to be more effective managers.

Our training offerings provide staff with a variety of opportunities to learn, enhance and practice fundamental leadership skills to enable them to be more effective in their roles and develop their skills for further growth.

We also train relevant members of our team on important environmental health and safety topics to help ensure we protect our people and our environment as we operate our business.

We encourage our employees to participate and take advantage of a variety of learning and development resources, including online business skills courses, professional development events, and external training programs based on individual needs.

We encourage our employees to participate

and take advantage of a variety of learning and development resources, including online business skills courses, professional development events, and external training programs based on individual needs.

We also actively review employee performance and business needs every six months that lead to promotional opportunities for employees across departments and levels.

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

What changed 10-K

Item 1. Business