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Item 1. Business

2023-02-28 compared with 2022-02-23 · 292 added, 312 removed, 748 unchanged (45% of the section changed)

We are a clinical stage immuno-oncology company pioneering the development of genetically engineered allogeneic T cell therapies for the treatment of cancer.

We are a clinical stage immuno-oncology company pioneering the development of genetically engineered allogeneic T cell product candidates for the treatment of cancer.

We are developing a pipeline of off-the-shelf T cell product candidates that are designed to target and kill cancer cells.

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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.

Our off-the-shelf approach is dependent on state-of-the-art manufacturing processes, and we are continuing to build a technical operations

organization with fully integrated in-house expertise in clinical and commercial engineered T cell manufacturing.

In February 2019, we entered into a lease to construct our own cell therapy manufacturing facility in Newark, California, and we commenced current good manufacturing practices (cGMP) manufacturing at our facility in 2021.

Finally, we plan to leverage next generation technologies to develop more potent product candidates and to develop product candidates from a renewable cell source.

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 are continuing to build a technical operations organization with fully integrated in-house expertise in clinical and commercial engineered T cell manufacturing.

We have built our own current good manufacturing practices (cGMP) manufacturing facility in Newark, California, that we call Cell Forge 1 (CF1).

We are currently assessing the product candidates for manufacturing at CF1.

Finally, we plan to leverage next generation technologies, such as to develop more potent product candidates and to develop product candidates to overcome premature rejection of allogeneic CAR T cells by the patient immune system.

We believe next generation technologies will also allow us to develop allogeneic T cell therapies for the treatment of solid tumors, which to date have been difficult to treat because of the lack of validated targets and tumor microenvironments that can impair the activity of T cells.

We are currently developing a pipeline of multiple allogeneic CAR T cell product candidates utilizing protein engineering, gene editing, gene insertion and advanced proprietary T cell manufacturing technologies.

Our most advanced product candidates, ALLO-501 and ALLO-501A, are engineered allogeneic CAR T cell therapies that target CD19, a protein expressed on the cell surface of B cells and a validated target for B cell driven hematological malignancies.

Our most advanced product candidates, ALLO-501 and ALLO-501A, are engineered allogeneic CAR T cell product candidates that target CD19, a protein expressed on the cell surface of B cells and a validated target for B cell driven hematological malignancies.

We are also developing engineered allogeneic CAR T cell product candidates for multiple myeloma, clear cell renal cell carcinoma (ccRCC), and other blood cancers and solid tumors.

Our pipeline is represented in the diagram below.

1 Servier holds ex-US commercial rights.

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

3 Allogene sponsored trial in combination with SpringWorks Therapeutics, Inc.

4 ALLO-647 intended to enable expansion and persistence of allogeneic CAR T product candidates.

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

Our lead product candidates include:

We are sponsoring a Phase 1 clinical trial (the ALPHA trial) of ALLO-501 in patients with the most common R/R non-Hodgkin lymphoma (NHL) subtypes, including R/R large B-cell lymphoma and R/R follicular lymphoma (FL).

We completed accrual in the ALPHA trial in 2021 and are following patients as part of long-term follow-up.

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We initiated a Phase 1/2 clinical trial for ALLO-501A (the ALPHA2 trial) in the second quarter of 2020.

The Phase 1 portion of the ALPHA2 trial is designed to assess the safety and tolerability at increasing dose levels of ALLO-501A in patients with R/R large B-cell lymphoma or transformed FL.

In December 2021, interim results from the ALPHA trial and ALPHA2 trial were presented at the American Society of Hematology (ASH) annual meeting.

See “—Product Pipeline and Development Strategy—Anti-CD19 Development Program—Results from the Phase 1 ALLO-501 ALPHA Trial and the Phase 1 ALLO-501A ALPHA2 Trial” for information regarding the results.

Subject to further patient follow-up and FDA discussion, we plan to proceed to the Phase 2 portion of the trial in adult patients with R/R large B-cell lymphoma in mid-2022.

The Phase 1 portion of the ALPHA2 trial was designed to assess the safety and tolerability at increasing dose levels of ALLO-501A in patients with R/R LBCL or transformed FL.

Updated results from the ALPHA trial and ALPHA2 trial were presented at our November 2022 R&D Showcase.

See “—Product

Pipeline and Development Strategy—Anti-CD19 Development Program—Results from the Phase 1 ALLO-501 ALPHA Trial and the Phase 1 ALLO-501A ALPHA2 Trial” for information regarding the results.

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 expect to complete enrollment of the Phase 2 portion of the ALPHA2 trial in the first half of 2024.

Subject to further patient follow-up and FDA discussion, we plan to initiate a Phase 3 clinical trial of ALLO-501A in an earlier line of therapy for LBCL in the first half of 2024.

We are sponsoring a Phase 1 clinical trial (the UNIVERSAL trial) of ALLO-715, an allogeneic CAR T cell product candidate targeting B-cell maturation antigen (BCMA), in adult patients with R/R multiple myeloma.

December 2021, interim results from the UNIVERSAL trial were presented at the ASH annual meeting.

We presented updated results from the UNIVERSAL trial at our R&D Showcase in November 2022 as well as at the American Society of Hematology annual meeting in December 2022.

See “—Product Pipeline and Development Strategy—Anti-BCMA Development Program—Results from the Phase 1 ALLO-715 UNIVERSAL Trial” for information regarding the results.

We are continuing the UNIVERSAL trial to further explore ALLO-715 and lymphodepletion dose and schedule.

• ALLO-715 plus nirogacestat .

In the first half of 2021, we expanded the UNIVERSAL trial to assess ALLO-715 in combination with SpringWorks Therapeutics, Inc.’s investigational gamma secretase inhibitor, nirogacestat.

We have dosed an initial cohort of patients that we are following prior to enrolling any further patients.

We are sponsoring a Phase 1 clinical trial (the IGNITE trial) of ALLO-605, an allogeneic CAR T cell product candidate targeting BCMA, in adult patients with R/R multiple myeloma.

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TurboCAR technology allows cytokine signaling to be engineered selectively into CAR T cells and has shown the ability to improve the potency and persistence of the cells and to delay exhaustion of the cells in preclinical models.

We are currently reviewing and optimizing the manufacturing process for our BCMA program and are not enrolling patients in the UNIVERSAL and IGNITE trials at this time.

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

Subject to results from the TRAVERSE trial, we also plan to investigate the use of ALLO-316 for other solid tumor and hematologic indications, such as acute myeloid leukemia (AML).

We presented preliminary results from the TRAVERSE trial at our November 2022 R&D Showcase.

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

Subject to ongoing results in the TRAVERSE trial, we intend to complete planned dose exploration and initiate expansion cohort enrollment in 2023.

We may also investigate the use of ALLO-316 for other CD70 expressing solid tumors and hematologic indications or in combination with other anticancer therapies such as immune checkpoint inhibitors.

We are developing an anti-CD52 monoclonal antibody, ALLO-647, which is a 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.

We are currently utilizing ALLO-647 in all of our clinical trials and plan to assess ALLO-647 in a separate registration trial that we plan to initiate in mid-2022 subject to the advancement of the ALPHA2 trial.

We expect to assess the safety of ALLO-647 and its contribution to the overall benefit to risk ratio of the lymphodepletion regimen through a randomized study with a cohort of patients that do not receive ALLO-647.

We are currently assessing ALLO-647 in all of our clinical trials and are in the process of initiating a separate Phase 2 trial (the EXPAND trial) to assess ALLO-647 and its contribution to the overall benefit to risk ratio of the lymphodepletion regimen for ALLO-501A.

We expect the EXPAND trial to open to enrollment early in the second quarter of 2023.

As a part of this potentially registrational trial, patients will be randomized to receive the same single dose of ALLO-501A as in the ALPHA2 trial and either lymphodepletion with fludarabine and cyclophosphamide (control arm) or the lymphodepletion regimen of the ALPHA2 trial, inclusive of ALLO-647 (active arm).

Our History and Team

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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 collaboration with Servier to develop and commercialize ALLO-501 and ALLO-501A, and we hold the commercial rights to these product candidates in the United States.

We have an Exclusive License and Collaboration Agreement with Servier (the Servier Agreement) to develop and commercialize ALLO-501 and ALLO-501A, and we hold the commercial rights to these product candidates in the United States.

We also have an exclusive worldwide license from Cellectis to its TALEN gene-editing technology for the development of allogeneic T cell product candidates directed against 15 different cancer antigens.

Our collaboration with Servier is intended to give us access to TALEN gene-editing technology for all product candidates we are co-developing.

In connection with the Pfizer asset acquisition, we hired a team of employees from Pfizer, who are primarily research and technical operation employees and were leading the research and development of our product candidates and next generation gene engineering and cell engineering technologies at Pfizer.

The Servier Agreement gives us access to TALEN gene-editing technology for ALLO-501 and ALLO-501A.

Our world-class management team has significant experience in immuno-oncology and in progressing products from early stage research to clinical trials, and ultimately to regulatory approval and commercialization.

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Chang led the development and approval of Yescarta at Kite.

Additionally, our Executive Vice President of Research and Development and Chief Medical Officer, Dr.

Rafael Amado, has more than 15 years of experience in biotechnology and he most recently served as President, Research and Development, at Adaptimmune Therapeutics plc, a T cell therapy company.

Our Chief Technical Officer, Alison Moore, Ph.D., has over 25 years of experience in biotechnology and was previously Senior Vice President, Process Development at Amgen, where she led the development, deployment and oversight of manufacturing for approximately 80 multi-modality assets.

Additionally, our Executive Vice President of Research and Development, Dr.

Zachary Roberts, was also instrumental in the development and execution of the clinical trials of Yescarta across multiple indications, and he most recently served as the Chief Medical Officer of Instil Bio, a cell therapy company, where he led development of both clinical and pre-clinical programs.

Our Chief Technical Officer, Alison Moore,

Ph.D., has over 25 years of experience in biotechnology and was previously Senior Vice President, Process Development at Amgen, where she led the development, deployment and oversight of manufacturing for approximately 80 multi-modality assets.

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

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We believe developing allogeneic CAR T cell product candidates targeting CD19 is the next frontier in delivering potentially curative therapies against B-cell lymphomas and leukemias.

We are focused on advancing ALLO-501A and plan to proceed to the Phase 2 portion of the ALPHA2 trial in mid-2022.

We are focused on advancing ALLO-501A with the goal to complete enrollment in our Phase 2 ALPHA2 trial for R/R LBCL in the first half of 2024.

We also plan to initiate a Phase 3 trial of ALLO-501A in an earlier line of therapy for LBCL in the first half of 2024.

• Expand our leadership position within hematologic indications .

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We believe a critical component to our success will be to leverage and expand our proprietary manufacturing know-how, expertise and capacity.

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.

We completed the build-out of the majority of the facility at the end of 2020 and commenced manufacturing under cGMP in 2021.

We believe establishing our own fully integrated manufacturing operations and infrastructure will allow us to improve the manufacturing process, limit our reliance on contract manufacturing organizations (CMOs) and more rapidly advance the commercialization of any of our product candidates that receive regulatory approval.

For instance, for our lead product candidate, ALLO-501A, we were able to identify and select a manufacturing process that was associated with robust clinical performance in Phase 1.

We call this process Alloy and are using the Alloy process to manufacture ALLO-501A for the ALPHA2 and EXPAND trials.

We plan to continue to optimize manufacturing for our other product candidates and plan to manufacture product at CF1, our state-of-the-art cell therapy manufacturing facility in Newark, California.

We believe establishing our own fully integrated manufacturing operations and infrastructure will allow us to continuously improve the manufacturing process, limit our reliance on contract manufacturing organizations (CMOs) and more rapidly advance the commercialization of any of our product candidates that receive regulatory approval.

• Expand into solid tumor indications with high unmet need and leverage next generation technologies to advance our platform.

We plan to continue to advance the research and development of product candidates directed against a broad portfolio of solid tumor targets, including CD70 for the treatment of ccRCC and DLL3 for the treatment of small cell lung cancer and other aggressive neuroendocrine tumors.

We plan to continue to advance the research and development of product candidates directed against a broad portfolio of solid tumor targets, including CD70 for the treatment of ccRCC, DLL3 for the treatment of small cell lung cancer and other aggressive neuroendocrine tumors, and Claudin 18.2 for the treatment of gastric and pancreatic cancer.

We also plan to leverage next generation technologies to make more potent allogeneic CAR T cells and improve the characteristics of our product candidates.

For example, we are advancing a clinical trial of a TurboCAR product candidate, ALLO-605, in R/R multiple myeloma.

We are also advancing modified next-generation TurboCARs to overcome some of the challenges of the solid tumor microenvironment.

In addition, we are investigating next-generation technologies to overcome rejection of allogeneic CAR T cells by the patient immune system and to increase specificity of CAR T activity to avoid potential normal tissue toxicities associated with certain solid tumor targets.

In collaboration with Notch Therapeutics Inc.

(Notch), we are researching and developing a process for production of product candidates derived from induced pluripotent stem cells (iPSCs).

We believe iPSCs may provide renewable starting material for our allogeneic CAR T cell product candidates that could allow for improved efficiency of gene editing, greater scalability of supply, product homogeneity and more streamlined manufacturing.

In addition, 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.

In addition, we are investigating next-generation technologies to control rejection of allogeneic CAR T cells by the patient immune system, such as with 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.

• Accelerate the development of our product candidates across geographies .

We are positioning ourselves to pursue clinical development of product candidates in additional markets around the world.

Subject to our clinical progress in the United States, we plan to initiate clinical trials in Europe.

Subject to our clinical progress in the United States, we plan to initiate clinical trials in Europe, Canada and Australia, among other geographies.

In addition, in December 2020, we jointly formed Allogene Overland Biopharm (CY) Limited for the development, manufacturing and commercialization of certain of our product candidates targeting BCMA, CD70, FLT3, and DLL3 in China, Taiwan, South Korea and Singapore.

We plan to support the operations of this joint venture as it advances and we may selectively partner with other third parties to develop and commercialize our product candidates in additional countries.

Allogene Overland has completed the buildout of a cell manufacturing facility in China and is beginning to progress product manufacturing ahead of clinical trial evaluation.

We may selectively partner with other third parties to develop and commercialize our product candidates in additional countries.

Allogeneic T Cell Therapy

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These receptors contribute to tumor surveillance by directing T cells to recognize and destroy cancerous cells.

When T cells with

cancer-specific receptors are absent, present in low numbers, of poor quality or rendered inactive by suppressive mechanisms, cancer may grow and spread.

When T cells with cancer-specific receptors are absent, present in low numbers, of poor quality or rendered inactive by suppressive mechanisms, cancer may grow and spread.

In addition, standard of care treatments, such as chemotherapy regimens, as well as disease specific factors can damage the patient’s immune system, thereby inhibiting the ability of T cells to kill cancer.

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

The autologous approach, pioneered by Novartis and Kite, has been highly successful in engineering patients’ immune systems to fight cancer, in particular CD19 positive cancers, resulting in significant remission rates.

The autologous approach, pioneered by Novartis and Kite, has been highly successful in engineering patients’ immune systems to fight cancer, in particular CD19 and BCMA expressing cancers, resulting in significant remission rates.

Autologous products are manufactured by first collecting a patient’s white blood cells, through a process known as leukapheresis, separating the T cells from the patient’s blood sample and proliferating the isolated T cells.

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Bridging therapy to control disease may increase some cumulative or synergistic toxicities for the patients.

Other rapidly progressing patients may not be considered candidates for autologous CAR T given lengthy waiting times.

Other rapidly progressing patients may not be considered candidates for autologous CAR T given lengthy waiting times and limited manufacturing slots.

• Variable Potency .

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We are investigating multiple constructs designed to mimic cytokine signaling selectively within CAR T cells, a technology platform that we call “TurboCARs”.

We are also exploring the use of genetic engineering to control immune rejection of allogeneic CAR T cells, such as with an anti-CD70 CAR, which we call Dagger, to recognize and destroy allo-reactive host immune cells that would otherwise be capable of rejecting the allogeneic CAR T cells.

Next, we use Cellectis’s electroporation and TALEN technologies for gene editing of T cells.

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This reaction, known as GvHD, is mediated by intact TCRs on allogeneic T cells.

To reduce the risk of GvHD, all of our product candidates undergo the inactivation of a gene coding for TCRα, a key component of TCRs.

The engineered T cells lacking functional TCRs are no longer capable of recognizing peptide

antigens presented on major histocompatibility complex proteins and thus incapable of attacking the patient’s normal tissue.

To reduce the risk of GvHD, all of our product candidates undergo the inactivation of a gene coding for

TCRα, a key component of TCRs.

The engineered T cells lacking functional TCRs are no longer capable of recognizing peptide antigens presented on major histocompatibility complex proteins and thus incapable of attacking the patient’s normal tissue.

This could mitigate the risk of GvHD that can occur when allogeneic TCR-positive T cells are infused into patients who are unrelated to the healthy donor, as shown in the figure below.

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To capitalize on this differentiation and to secure our own source of anti-CD52 monoclonal antibody, we are developing ALLO-647.

We are currently utilizing ALLO-647 in all of our clinical trials.

We are currently assessing ALLO-647 in all of our clinical trials and are in the process of initiating a potentially pivotal Phase 2 trial for ALLO-647 as part of the lymphodepletion regimen for ALLO-501A.

Purification, Formulation, and Storage

Once the allogeneic T cells have been engineered with CARs and gene edited to remove the genes encoding TCRα and CD52, they are cultured for several days to increase the cell number and then harvested.

The allogeneic cells then undergo a

purification step to remove residual TCR positive cells that have not undergone TCRα gene editing.

The allogeneic cells then undergo a purification step to remove residual TCR positive cells that have not undergone TCRα gene editing.

We believe this purification step is essential as none of the currently available gene-editing nucleases is 100% efficient at inactivating the target genes.

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Our product pipeline is represented in the diagram below:

1 Servier holds ex-US commercial rights.

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

3 Allogene sponsored trial in combination with SpringWorks Therapeutics, Inc.

4 ALLO-647 intended to enable expansion and persistence of allogeneic CAR T product candidates.

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

In October 2021, the FDA placed a hold on our clinical trials.

The clinical hold followed our notification to the FDA of a chromosomal abnormality in an ALPHA2 study patient which was detected in a bone marrow biopsy undertaken to assess pancytopenia.

Investigations concluded that the chromosomal abnormality was unrelated to TALEN gene editing or our

manufacturing process and had no clinical significance.

Investigations concluded that the chromosomal abnormality was unrelated to TALEN gene editing or our manufacturing process and had no clinical significance.

The investigation also determined that the abnormality was not detected in any of our manufactured product candidates or in any other patient treated with the same ALLO-501A lot.

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We believe CD19 is a validated target for the treatment of B cell leukemias and lymphomas.

Multiple autologous anti-CD19 targeted CAR T therapies have shown promising results and have been approved by the FDA as therapies for adults with R/R large B-cell lymphoma, adults with R/R mantle cell lymphoma, adults with R/R FL, and children and adults with R/R ALL.

Our first anti-CD19 product candidate, UCART19, was advanced with our partner, Servier, who led manufacturing and clinical development.

Multiple autologous anti-CD19 targeted CAR T therapies have shown promising results and have been approved by the FDA as therapies in multiple blood cancers, including R/R LBCL, as further described below under "—Competition".

Our first anti-CD19 product candidate, UCART19, was advanced with Servier, who led manufacturing and clinical development.

UCART19 was manufactured to express a CAR that is designed to target CD19 and gene edited to lack TCRα and CD52 to minimize the risk of GvHD and enable a window of persistence in the patient.

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Patients from both studies are continuing the long-term follow-up as planned.

We and Servier are reviewing our development strategy for ALL as our data matures and as we assess potential next generation technology that may be used to enhance results in ALL.

ALLO-501 and ALLO-501A are our other allogeneic CAR T cell product candidates targeting CD19, which are jointly developed by us and Servier.

We are reviewing our development strategy for ALL as our data matures and as we assess potential next generation technology that may be used to enhance results in ALL.

ALLO-501 and ALLO-501A are our other allogeneic CAR T cell product candidates targeting CD19, which are also part of the Servier Agreement.

We are responsible for the manufacture of ALLO-501 and ALLO-501A.

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Over 60 NHL subtypes have been identified, and each subtype represents different neoplastic lymphoid cells (T, B or NK cells) that have arrested at different stages of differentiation.

The most common subtype is B-cell, which represented over 90% of all new NHL cases in 2016.

According to the American Cancer Society, B-cell lymphomas make up approximately 85% of NHL cases in the United States.

B-cell NHL itself represents a group of different neoplasms that not only differ in pathology, but also response to therapy and prognosis.

NHL can be rapidly growing (aggressive) with short survival, such as large B-cell lymphomas, which include diffuse large B cell lymphoma (DLBCL), or it can be slow growing, or indolent, such as FL.

The R-CHOP chemotherapy combination (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) introduced in the early 2000s remains the standard of care for newly diagnosed DLBCL, and five-year survival can be achieved for 55-60% of patients.

Unfortunately, approximately 30% of DLBCL require second-line therapy, and subsequent therapy is dependent on whether the patients are candidates for high-dose therapy followed by autologous stem-cell therapy.

A retrospective analysis of patients with R/R DLBCL, who were not treated with autologous CAR T therapy, found that outcomes

in this population are poor, with an objective response rate of 26% (complete response (CR):

NHL can be rapidly growing (aggressive), such as large B-cell lymphomas, which include diffuse large B cell lymphoma (DLBCL), or it can be slow growing, or indolent, such as FL.

Unfortunately, approximately 30% of DLBCL relapse and require second-line therapy.

Subsequent therapy for fit patients is commonly high-dose therapy followed by autologous stem-cell therapy or autologous anti-CD19 CAR T therapy.

Two recent randomized controlled trials evaluated anti-CD19 CAR T cell therapies, Yescarta and Breyanzi, compared to high dose chemotherapy followed by autologous stem cell rescue.

Yescarta and Breyanzi improved event-free-survival versus stem cell transplant (8.3 months vs.

2.0 months and 10.1 months vs.

2.3 months, respectively).

Overall survival from these randomized trials is pending;

however, a retrospective analysis of patients with R/R DLBCL, who were not treated with autologous CAR T therapy, found that outcomes in this population are poor, with an objective response rate of 26% (complete response (CR):

7%, partial response:

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In these patients, the toxicity commonly outweighs the benefit of treatment with chemotherapy.

Autologous CAR T therapy has made significant advances in addressing R/R NHL, and may move to earlier lines of therapy, as further described below under "—Competition".

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

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

In December 2021 at the ASH annual meeting, we, in collaboration with Servier, announced interim results from the Phase 1 ALPHA trial of ALLO-501 and from the Phase 1 ALPHA2 trial of ALLO-501A.

The ALPHA and ALPHA2 trial enrollment information is set forth in the table below.

Data Cutoff October 18, 2021

Enrolled 50 29

Evaluable for Safety 49* 28**

Evaluable for Efficacy 40 #

% Initiated Treatment 98% 97%

Median Days Enrollment to Treatment Initiation 5 2

* One patient unable to be treated due to rapidly progressing disease

** One patient developed COVID-19 before treatment

# Only CAR T Naïve subjects presented from ALPHA at ASH 2021

† One patient started lymphodepletion but became ineligible due to central nervous system disease progression;

two treated patients yet to reach tumor assessment at data cutoff

Patients received lymphodepletion (LD) containing fludarabine (30mg/m 2 x 3 days), cyclophosphamide (Cy) (300mg/m 2 x 3 days) and ALLO-647 (30, 60 or 90mg) followed by escalating dose levels (DL) of ALLO-501 or ALLO-501A.

In consolidation, patients with stable disease or better at day 28 received a chemotherapy-free lymphodepletion (ALLO-647 only) and allogeneic CAR T cell infusion (120 x 10 6 CAR+ T cells).

The trials explored two consolidation cohorts.

Consolidation 1 used the standard Cy dosing (300mg/m 2 x 3 days).

Consolidation 2 explored a higher Cy dose (500mg/m 2 x 3 days).

Response Rates Across the ALPHA and ALPHA2 Trials

ALPHA ALLO-501 Response Rates

Follicular Lymphoma (FL) Large B Cell Lymphoma (LBCL)

Single dose (N=18) Consolidation

(N=26) Single dose

(N=11) Consolidation

(N=3) All LBCL

(N=14) All Patients

On November 29, 2022, we, in collaboration with Servier, announced results from the Phase 1 ALPHA trial of ALLO-501 and from the Phase 1 ALPHA2 trial of ALLO-501A in R/R LBCL at our R&D Showcase.

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 ALLO-501A and ALLO-647.

In addition, following a review of the Phase 1 program, we determined that our Alloy manufacturing process was associated with robust performance.

Alloy is being deployed in the ongoing Phase 2 ALPHA2 trial.

A single infusion of CAR+ cells with a lymphodepletion regimen consisting of fludarabine (30 mg/m2/day x 3 days) and cyclophosphamide (300 mg/m2/day x 3 days) (standard flu/cy) plus 90 mg of ALLO-647 (Single Dose FCA90) was deemed preferable to two infusions of CAR+ cells (Consolidation Regimen).

In the Consolidation Regimen, ALLO-647 dosing was split into 60 mg and 30 mg prior to the first and second infusion of CAR+ cells.

This finding underscores the importance of optimizing lymphodepletion in allogeneic cell therapy.

Data from the Phase 1 trials of ALLO-501 and ALLO-501A support the ability of a single administration of CAR T cells to generate deep and durable responses.

As of the October 25, 2022 data cutoff, 33 autologous CAR T naïve patients with r/r LBCL were treated with Alloy process material.

Ninety-two percent (92%) of all enrolled patients received investigational product with 100% of infused product manufactured and released as per product specifications.

Patients were able to initiate treatment within two days of enrollment.

Responses in the ALPHA trials were overall durable.

Of the nine patients treated with Alloy process material who achieved a complete response (CR) at six months, eight remained in remission with the longest CR ongoing at 26+ months as of the data cutoff.

Among 12 patients treated with the Single Dose FCA90 regimen, the overall response rate (ORR) was 67% and 58% achieved CRs.

Among the eight patients in the Single Dose FCA90 cohort who had the opportunity to be followed for six months or more, four (50%) were in CR at both six and 12 months.

Alloy Process

(n = 48) All Alloy

(n=33) Consolidation Regimen (n=15) Single Dose FCA90

Overall Response Rate (ORR), n (%) 23 (48) 19 (58) 8 (53) 8 (67)

CR, n (%) 9 (50%) 6 (75%) 15 (58%) 5 (45%) 1 (33%) 6 (43%) 21 (53%)

Consolidation 1 and 2 combined due to limited sample size at the time of the data cutoff

Among the 21 FL patients and 11 LBCL patients who were autologous CAR T naïve, 33% and 36% achieved a CR at six months.

With the exception of one previously disclosed patient who died from unrelated arrhythmia, all LBCL patients who achieved a CR at month six remained in CR with the longest ongoing CR at 18+ months as of the data cutoff.

ALPHA2 ALLO-501A Response Rates

(N=6) Consolidation 1

(N=9) Consolidation 2

(N=10) All Patients

ORR, n (%) 2 (33%) 4 (44%) 6 (60%) 12 (48%)

CR, n (%) 2 (33%) 4 (44%) 1 (10%) 7 (28%)

Longest CR (months) 15+ 9+ 4+ 15+

As of the data cutoff, all ALPHA2 patients who achieved a CR at month six remained in CR with the longest ongoing CR at 15+ months and longest ongoing CRs in the consolidation cohort at 9+ months.

Combined ALPHA + ALPHA2 Consolidation Response Rates

Consolidation 1 Consolidation 2 All Patients

N = 16 N = 14 N = 30

ORR, n (%) 9 (56%) 10 (71%) 19 (63%)

CR, n (%) 7 (44%) 5 (36%) 12 (40%)

All dose schedules suggest clinically encouraging activity with respect to ORR and CR.

Safety Across the ALPHA and ALPHA2 Trials

ALLO-501 and ALLO-501A were associated with consistent and manageable safety with no dose limiting toxicities (DLTs) or GvHD, and minimal Grade 3 Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) , or Grade 3 cytokine release syndrome (CRS).

ALPHA ALLO-501 Safety

(N=4) DL2 120M (N=16) DL3 360M (N=18) Consolidation (N=11) All Patients (N=49)

All Gr3+ All Gr3+ All Gr3+ All Gr3+ All Gr3+

IRR* 50% 0 69% 6% 61% 0 64% 18% 63% 6%

CRS 0 0 31% 6% 33% 0 27% 9% 29% 4%

Neurotoxicity 25% 0 25% 6% 22% 0 36% 9% 27% 4%

GvHD 0 0 0 0 0 0 0 0 0 0

Infection 75% 0 63% 38% 61% 17% 64% 36% 63% 27%

Neutropenia 100% 75% 75% 75% 83% 72% 82% 64% 82% 71%

Serious Adverse Event (AE) 25% 56% 28% 27% 37%

*Infusion-related reactions (IRR).

Grade 3+ infection rates were observed at a rate similar to that seen in autologous CAR T trials.

There were five treatment-emergent deaths in the absence of disease progression, all of which were previously reported.

ALPHA2 ALLO-501A Safety

(N=1) DL2 120M

(N=6) Consolidation 1 (N=11) Consolidation 2

(N=10) All Patients (N=28)

All Gr Gr 3+ All Gr Gr 3+ All Gr Gr 3+ All Gr Gr 3+ All Gr Gr 3+

IRR 100% 0 33% 0 27% 0 10% 0 25% 0

Complete Response (CR), n (%) 14 (29) 14 (42) 6 (40) 7 (58)

6 Month CR Rate, n (%) 9 (23) 9 (31) 5 (33) 4 (50)

12 Month CR Rate, n (%) 8 (21) 8 (28) 4 (27) 4 (50)

The ALPHA Phase 1 trials demonstrated a manageable safety profile.

There were no observed dose limiting toxicities (DLTs) or graft-vs-host disease (GvHD).

Among patients treated with Single Dose FCA90, there was no Grade 3+ cytokine

release syndrome (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.

Alloy Process

(n=48) All Alloy

(n=33) Consolidation Regimens

(n=15) Single Dose

Adverse Events of Interest All Grs

n (%) All Grs

CRS 11 (23) 0 8 (24) 0 3 (20) 0 4 (33) 0

Neurotoxicity 15 (31) 3 (6) 12 (36) 2 (6) 6 (40) 2 (13) 4 (33) 0

ICANS 1 (2) 0 0 0 0 0 0 0

GvHD 0 0 0 0 0 0 0 0

Infection 25 (52) 9 (19) 19 (58) 5 (15) 8 (53) 3 (20) 8 (67) 1 (8)

Neutropenia 0 0 100% 100% 36% 36% 60% 60% 57% 57%

Serious AE 0 100% 18% 30% 39%

The safety profile of ALLO-501A was manageable in both the single-dose and both consolidation cohorts.

There were no treatment-emergent deaths in the trial.

A chromosomal abnormality was observed in a patient in Consolidation 2 that led to a clinical hold on our clinical trials.

The abnormality was investigated, which resulted in the resolution of the clinical hold on our clinical trials.

Prolonged Gr3+ cytopenia — 9 (19) — 4 (12) — 2 (13) — 2 (17)

Clinical Development Plan

The ALPHA trial is an open-label, Phase 1, single arm, multicenter clinical trial evaluating the safety and tolerability of ALLO-501 in adult patients with R/R large B-cell lymphoma, including DLBCL, or FL.

The ALPHA trial is an open-label, Phase 1, single arm, multicenter clinical trial evaluating the safety and tolerability of ALLO-501 in adult patients with R/R LBCL, including DLBCL, or FL.

We completed accrual in the ALPHA trial in 2021 and are following patients as part of long-term follow-up.

In the second quarter of 2020, we initiated ALPHA2, which is an open-label, Phase 1/2, single arm, multicenter clinical trial evaluating the safety and efficacy of ALLO-501A in adult patients with R/R large B-cell lymphoma, including DLBCL, or transformed FL.

Cell kinetics and pharmacodynamics of ALLO-501A will be evaluated as secondary and exploratory objectives, respectively.

The Phase 1 portion of the ALPHA2 trial is designed to assess the safety and tolerability at increasing dose levels of ALLO-501A and consolidation of ALLO-501A dosing, in order to identify the recommended doses and schedule of ALLO-501A and the lymphodepletion regimen for use in the Phase 2 portion of the trial.

We plan to seek agreement with the FDA to proceed to Phase 2 on matters such as chemistry, manufacturing and controls (CMC), including for the use of ALLO-501A manufactured at our own manufacturing facility, and trial designs to evaluate both ALLO-501A and ALLO-647.

Subject to FDA discussion and further patient follow-up, we plan to proceed to the Phase 2 portion of the trial in adult patients with R/R large B-cell lymphoma in mid-2022.

Prior to initiating Phase 2, we plan to continue to enroll patients in the Phase 1 portion of the trial.

The ALPHA2 trial is an open-label, Phase 1/2, single arm, multicenter clinical trial evaluating the safety and efficacy of ALLO-501A in adult patients with R/R large B-cell lymphoma, including DLBCL, or transformed FL.

Cell kinetics and pharmacodynamics of ALLO-501A are evaluated as secondary and exploratory objectives, respectively.

The Phase 1 portion of the ALPHA2 trial was designed to assess the safety and tolerability at increasing dose levels of ALLO-501A and consolidation of ALLO-501A dosing, in order to identify the recommended doses and schedule of ALLO-501A and the lymphodepletion regimen for use in the Phase 2 portion of the trial.

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

The single-arm Phase 2 ALPHA2 trial is utilizing a single dose of ALLO-501A (120 million CAR+ cells) with the FCA90 lymphodepletion regimen.

The ALPHA2 trial will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy.

The primary endpoint of this trial is ORR, and the key secondary endpoint is duration of response.

We expect to complete enrollment in the trial in the first half of 2024.

We are also preparing a Phase 3 trial of ALLO-501A in an earlier line of therapy for LBCL, which we expect to initiate in the first half of 2024.

We are also advancing the EXPAND trial of ALLO-647, which is expected to enroll approximately 70 patients with R/R LBCL and is intended to demonstrate the overall contribution of ALLO-647 to the benefit to risk ratio of the lymphodepletion regimen for ALLO-501A.

Patients will be randomized to receive the same single 120 million CAR+ cell dose of ALLO-501A as in the ALPHA2 trial and either lymphodepletion with fludarabine and cyclophosphamide (control arm) or the lymphodepletion regimen of the ALPHA2 trial, inclusive of ALLO-647 (active arm).

We expect the EXPAND trial to open to enrollment early in the second quarter of 2023.

Assuming favorable outcomes and subject to FDA discussions, we plan to seek FDA approval of ALLO-501A and ALLO-647 on the basis of the ALPHA2 trial and the EXPAND companion trial.

Anti-BCMA Development Program

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We believe BCMA is an appropriate target for the treatment of multiple myeloma.

Several autologous anti-BCMA targeted CAR T therapies have shown promising results in clinical trials, one of which has been approved by the FDA for adult patients with R/R multiple myeloma.

We are currently advancing a three-part strategy for the treatment of multiple myeloma.

First, we are advancing ALLO-715, an anti-BCMA allogeneic CAR T cell product candidate.

Autologous anti-BCMA targeted CAR T therapies have shown promising results in clinical trials and have been approved by the FDA for adult patients with R/R multiple myeloma, as further described below under "—Competition".

ALLO-715 is our first anti-BCMA allogeneic CAR T cell product candidate assessed in the clinic.

ALLO-715 is manufactured to express a CAR that is designed to target BCMA and gene edited to lack TCRα and CD52 to minimize the risk of GvHD and enable a window of persistence in the patient when dosed in combination with ALLO-647.

In addition, rituximab recognition domains, as an off-switch, have been incorporated in between the scFv and the linker domain.

Second, as part of the ongoing Phase 1 clinical trial (the UNIVERSAL trial) of ALLO-715 in adult patients with R/R multiple myeloma, we are assessing the combination of ALLO-715 with SpringWorks Therapeutics, Inc.’s investigational gamma secretase inhibitor, nirogacestat.

Gamma secretase inhibition prevents the cleavage and shedding of BCMA from the surface of myeloma cells.

In preclinical models, nirogacestat has been shown to increase the cell surface density of BCMA and reduce levels of soluble BCMA, thereby enhancing the activity of BCMA-targeted therapies.

Third, we are progressing our next-generation version of ALLO-715, known as ALLO-605, that incorporates our TurboCAR technology to allow cytokine signaling to be engineered selectively into CAR T cells.

In addition, rituximab

recognition domains, as an off-switch, have been incorporated in between the scFv and the linker domain.

We are conducting a Phase 1 clinical trial (the UNIVERSAL trial) of ALLO-715 in adult patients with R/R multiple myeloma.

Our next-generation version of ALLO-715, known as ALLO-605, incorporates our TurboCAR technology to allow cytokine signaling to be engineered selectively into CAR T cells.

TurboCARs have shown the ability to improve the potency and persistence of the CAR T cells and to delay exhaustion of the CAR T cells in preclinical models.

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Multiple myeloma predominantly affects the elderly, with 14 times more patients diagnosed at age 65 and over than those diagnosed under the age of 65.

For patients less than age of 70 with no comorbidities, autologous stem cell therapy is the preferred option to provide a durable response.

For patients under the age of 70 with no comorbidities, autologous stem cell therapy is the preferred option to provide a durable response.

For transplant ineligible patients, immunomodulatory drugs (Revlimid, Pomalyst, Thalomid) and proteasome inhibitors (Velcade, Kyrprolis, Ninlaro), often used in combination with one another, have displaced older cytotoxic agents as the mainstay of treatment.

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Despite the introduction of newer therapies, a majority of patients are expected to relapse and the unmet need in patients with R/R myeloma remains high.

In clinical trials, only 3% of patients who were previously treated with at least three lines of therapy (including proteasome inhibitors and immunomodulatory drugs), or who were refractory to both proteasome inhibitors and immunomodulatory drugs, achieved a CR to Darzalex, a CD38-directed monoclonal antibody.

Median survival in such patients was just 17.5 months.

Trials of autologous CAR T cell therapies have shown significant promise in multiple myeloma with reported CR rates that are substantially higher, and the first autologous CAR T cell therapy was approved in 2021.

In patients who have developed progressive disease following exposure to all five classes of non-cytotoxic therapies, options are limited.

Cytotoxic chemotherapy-containing regimens are reserved for fit patients, are given as continuous infusions and are associated with significant toxicity and generally limited efficacy.

The single agent selexinor (Xpovio) has been studied as a single agent in patients with disease refractory to all five classes of novel agents and is associated with an ORR of 26%, a median duration of response of 4.4 months and toxicity that required discontinuation of treatment in 18% of patients.

Trials of anti-BCMA therapies including bispecific antibodies and autologous CAR T cell therapies have shown significant promise in multiple myeloma with reported CR rates that are substantially higher in patients with R/R myeloma.

There are two autologous CAR T cell therapies and one bispecific antibody currently commercially available.

Results from the Phase 1 ALLO-715 UNIVERSAL Trial

In December 2021 at the ASH annual meeting, we announced interim results from the Phase 1 UNIVERSAL study of single dose ALLO-715 in R/R multiple myeloma.

As of the October 14, 2021 data cutoff, 48 patients were enrolled with 43 patients evaluable for safety and efficacy.

Patients were refractory to their last line of myeloma therapy, had a median of five prior lines of therapy, and 42% were penta-refractory meaning the disease has ultimately become nonresponsive to other approved therapies.

Five patients became ineligible for treatment due to rapidly progressing disease.

The median time from enrollment to the start of therapy was five days.

The Phase 1 UNIVERSAL trial evaluated lymphodepletion followed by ALLO-715 at one of four dose levels (DL1=40M cells, DL2=160M cells, DL3=320M cells, DL4 = 480M cells) and two LD regimens (FCA:

fludarabine, Cy and ALLO-647 or CA:

Cy and ALLO-647 only).

The updated presentation primarily focused on the optimized DL3 cell dose and FCA lymphodepletion.

The higher CAR T cell doses were associated with an increased response rate and greater allogeneic CAR T cell expansion.

In the DL3 cohort which was selected for cohort expansion, the ORR was 71% with 46% of patients achieving a very good partial response (VGPR) or better (VGPR+).

VGPR+ is defined as a stringent complete response (sCR), CR or VGPR.

Of the patients who achieved VGPR+, 92% were Minimal Residual Disease negative.

Cell dose and LD regimen DL3 320 x 10 6 CAR+ cells

(N=11) Mid ALLO-647

(N=10) High ALLO-647

(N=3) ALL ALLO-647

On November 29, 2022, we announced results from the Phase 1 UNIVERSAL trial of ALLO-715 in patients with R/R multiple myeloma.

Dose expansion cohorts comprised of a single dose of ALLO-715 (320 million CAR+ cells) and either FCA39 lymphodepletion (standard flu/cy plus 39 mg of ALLO-647) or FCA60 lymphodepletion (standard flu/cy plus 60 mg of ALLO-647) demonstrated substantial and durable responses.

Importantly, 92% of all enrolled patients received investigational

product with 100% of infused product manufactured and released as per product specifications.

Patients were able to initiate treatment within five days of enrollment and no bridging therapy was required.

Through a median follow-up of 14.8 months as of the October 11, 2022 data cutoff, the ORR was 67% in the FCA60 cohort and the very good partial response or better rate (VGPR+) was 42%.

All VGPR+ were minimal residual disease (MRD) negative.

The median duration of response was 9.2 months, with the longest ongoing response at 24 months.

Expansion Cohorts

LD Regimen Total

(n=23*) FCA39

ORR*, n (%) 15 (65) 7 (64) 8 (67)

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CR/sCR rate, n (%) 5 (22) 3 (27) 2 (17)

As of the data cutoff, the overall median follow-up for efficacy was 3.8 months.

The median duration of response was 8.3 months, with nine patients remaining in ongoing response at the time of the data cut-off.

The longest ongoing response after cell infusion was 12 months.

Of the 43 patients evaluable for safety, there was no GvHD.

Grade 1 and 2 CRS was reported in 23 patients (53%) and was manageable with standard therapies.

In this heavily pre-treated patient population, infection occurred in 54% of patients, which included three Grade 5 infections, as previously reported.

Grade 3+ neutropenia occurred in 70% of patients.

Six patients (14%) experienced adverse events of low-grade neurotoxicity, which was reversible.

Use of tocilizumab and steroids was infrequent (23% and 14%, respectively).

Adverse Events of Interest Grade 1

N (%) Grade 2

N (%) Grade 3

N (%) Grade 4

Median DOR 8.3 8.3 9.2

* Five patients with best responses ranging from stable disease to partial response were not included due to limited follow-up.

Safety profile was manageable with low-grade and reversible neurotoxicity and no GvHD.

In the expansion cohorts, there was low use of tocilizumab (32%) and steroids (25%).

Eight patients (29%) experienced Grade 3+ infections and prolonged Grade 3+ cytopenias.

As previously reported, one Grade 5 event occurred in the expansion cohorts and no new Grade 5 events have occurred.

Expansion Cohorts

Adverse Events of Interest All Grades

n (%) Grade 3+

N (%) All Grades

CRS 19 (68) 1 (4)

Neurotoxicity 17 (61) 0

GvHD 0 0 0 0 0 0

ICANS 1 (4) 0

Infection 19 (68) 8 (29)

Infusion Reaction to ALLO-647 7 (16%) 5 (12%) 0 0 0 12 (28%)

Prolonged Gr3+ Cytopenia — 8 (29)

Clinical Development Plan

The UNIVERSAL and IGNITE trials are open-label, Phase 1, single-arm, multicenter clinical trials evaluating the safety and tolerability of ALLO-715 and ALLO-605, respectively, in adult patients with R/R multiple myeloma.

The safety of ALLO-647, cell kinetics, pharmacodynamics, and efficacy will be evaluated as secondary objectives.

We are exploring the optimal dose and schedule of ALLO-715 and ALLO-605 and the lymphodepletion regimen, including the dose of ALLO-647.

The safety of ALLO-647, cell kinetics, pharmacodynamics, and efficacy are evaluated as secondary objectives.

In the first half of 2021, the UNIVERSAL trial initiated the evaluation of ALLO-715 in combination with nirogacestat.

Prior to ALLO-715 and nirogacestat treatment, all patients undergo lymphodepletion with a regimen of fludarabine, cyclophosphamide and ALLO-647.

The combination cohort will assess the safety and tolerability of ALLO-715 in combination with nirogacestat.

The preliminary anti-tumor activity of the combination, cell kinetics, pharmacokinetics and host immune cell depletion/reconstitution will be evaluated as secondary objectives.

We have dosed an initial cohort of patients that we are following prior to enrolling any further patients.

We expect to provide an update on our BCMA program by the end of 2022.

We dosed an initial set of patients in the combination cohort and made the decision not to advance ALLO-715 in combination with nirogascestat into dose expansion cohorts.

We are currently reviewing and optimizing the manufacturing process for our BCMA program in order to improve and obtain more consistent clinical results and are not enrolling patients in the UNIVERSAL and IGNITE trials at this time.

Anti-CD70 Development Program

CD70 is an antigen selectively expressed on several types of cancer cells, with strong expression in ccRCC and limited off-tumor expression.

CD70 is selectively expressed in a portion of other solid tumors, such as glioblastoma multiforme, non-small cell lung cancer, cervical or ovarian cancer, and head and neck cancer, and blood cancers, such as acute myeloid leukemia, DLBCL, multiple myeloma, and chronic lymphocytic leukemia.

CD70 is selectively expressed in a portion of other solid tumors and blood cancers.

While CD70 can be expressed on activated T cells, ALLO-316 was associated with minimal or no fratricide in preclinical studies, meaning that ALLO-316 cells did not mediate the targeted killing of other ALLO-316 cells.

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ALLO-316 is manufactured to express a CAR that is designed to target CD70 and gene edited to lack TCRα and CD52 to minimize the risk of GvHD and enable a window of persistence in the patient when dosed in combination with ALLO-647.

In addition, rituximab and CD34 recognition domains have been incorporated in between the scFv and the linker domain, as illustrated below.

The rituximab recognition domains allow elimination of cells with rituximab in the event that silencing of

CAR T cell activity is desired.

In addition, rituximab and CD34 recognition domains have been incorporated in between the scFv and the linker domain, as

illustrated below.

The rituximab recognition domains allow elimination of cells with rituximab in the event that silencing of CAR T cell activity is desired.

The CD34 domain confers recognition by an anti-CD34 antibody, and may be used as a surface marker to monitor ALLO-316 in patients by flow cytometry.

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sunitinib) represented a first-line standard for over a decade, these therapies have been quickly supplanted by combination therapies incorporating PD-1 immune-checkpoint inhibition as the backbone.

The combination of VEGF and immune check-point inhibitors, such as axitinib and pembrolizumab, are often used in the first line setting and has shown a median progression-free survival of 15.1 months with an ORR of 59.3% and CR rate of 5.8%.

The combination of VEGF and immune check-point inhibitors, such as axitinib and pembrolizumab, is often used in the first line setting and has shown a median progression-free survival of 15.1 months with an ORR of 59.3% and CR rate of 5.8%.

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

Results from the Phase 1 ALLO-316 TRAVERSE Trial

On November 29, 2022, we announced preliminary results from the Phase 1 TRAVERSE trial of ALLO-316 in patients with advanced or metastatic RCC who have progressed on or intolerant to standard therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.

Initial data from this trial has demonstrated the promise of an allogeneic CAR T product candidate to treat CD70 expressing RCC with ALLO-316 inducing anti-tumor activity.

Observed anti-tumor activity was largely confined to patients with CD70 expressing tumors.

As of the data extract date of November 17, 2022, in the nine 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.

(n=17) CD70+ Patients

ORR, n (%) 3 (18) 3 (33)

DCR, n (%) 14 (82) 9 (100)

PR, n (%) 3 (18) 3 (33)

ALLO-316 has demonstrated a generally manageable safety profile with no GvHD.

One dose limiting toxicity of 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 was low grade, reversible and seen in three patients (18%).

No grade 5 events have occurred.

CRS 11 (65) 1 (6)

Neurotoxicity 3 (18) 0

Infection 9 (53) 5 (30)

Prolonged Gr3+ Cytopenia — 3 (18)

Clinical Development Plan

The TRAVERSE trial is an open-label, Phase 1, single arm, multicenter clinical trial evaluating the safety and tolerability of ALLO-316 in adult patients with advanced or metastatic ccRCC.

Anti-tumor activity, cell kinetics, pharmacodynamics, and correlation of outcome with tumor CD70 expression will be evaluated as secondary objectives.

The trial is a dose-escalation study for ALLO-316 with separate dose cohorts.

Prior to ALLO-316 treatment, patients will undergo lymphodepletion with a regimen of fludarabine, cyclophosphamide and/or ALLO-647.

Subject to results from the TRAVERSE trial, we also plan to investigate the use of ALLO-316 for other solid tumor and hematologic indications, such as AML.

Anti-tumor activity, cell kinetics, pharmacodynamics, and correlation of outcome with tumor CD70 expression are evaluated as secondary objectives.

We have developed an investigational in vitro companion diagnostic (IVD) assay designed for use in determining CD70 expression levels for patient selection in TRAVERSE.

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, including FC and FCA in CD70 positive RCC patients.

Subject to ongoing results in the TRAVERSE trial, we intend to complete planned dose exploration and initiate expansion cohort enrollment in 2023.

We may also investigate ALLO-316 for other CD70 expressing solid tumors and hematologic indications or in combination with other anticancer therapies such as immune checkpoint inhibitors.

Future Opportunities

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These include the additional targets currently in our pipeline as well as other targets that might be validated in the future.

For example, we are developing allogeneic CAR T cell product candidates targeting FLT3 for the treatment of AML (ALLO-819) and DLL3 for the treatment of small cell lung cancer.

For example, we are developing allogeneic CAR T cell product candidates targeting FLT3 for the treatment of AML (ALLO-819), DLL3 for the treatment of small cell lung cancer and Claudin 18.2 for the treatment of gastric and pancreatic cancer.

We also plan to investigate the potential to enhance our platform using next-generation technologies such as TurboCARs, renewable cell sources, site-specific integration, multi-specific CARs and other technology related to enhancing specificity and avoiding immune rejection.

• Next-generation anti-rejection technology:

We are investigating additional ways, beyond our existing anti-CD52 antibody technology, to prevent premature patient immune rejection of our allogeneic CAR T cells.

We are exploring ways to engineer allogeneic CAR T cells to escape detection from the patient immune system, such as through our research collaboration with Antion Biosciences SA (Antion).

We are also exploring engineering allogeneic CAR T cells with mechanisms to attack certain patient immune cells that would otherwise lead to rejection.

For instance, based on initial data from the TRAVERSE trial that showed high CAR T cell expansion in patients, we are exploring utilizing an anti-CD70 CAR, which we call Dagger, to recognize and destroy allo-reactive host immune cells that would otherwise be capable of rejecting the allogeneic CAR T cells, which could provide enhanced persistence of the allogeneic CAR T cells.

• TurboCARs .

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believe TurboCARs may also allow for reduced CAR T cell dose requirements and greater impact in overcoming exhaustion in solid tumor environments.

We are advancing a Phase 1 clinical trial of our first TurboCAR, ALLO-605, which targets BCMA and uses a constitutive cytokine signaling domain and a rituximab-mediated off-switch.

• Renewable Cell Source.

In November 2019, we entered into a Collaboration and License Agreement with Notch (the Notch Collaboration Agreement), pursuant to which Notch has granted to us an exclusive, worldwide, royalty-bearing, license to certain Notch intellectual property to develop and commercialize gene-edited T cell and/or natural killer cell products from iPSCs directed at certain CAR targets for initial application in NHL, ALL and multiple myeloma.

In November 2019, we entered into a Collaboration and License Agreement (the Notch Collaboration Agreement) with Notch Therapeutics Inc.

(Notch), pursuant to which Notch has granted to us an exclusive, worldwide, royalty-bearing, license to certain Notch intellectual property to develop and commercialize gene-edited T cell and/or natural killer cell products from induced pluripotent stem cells (iPSCs) directed at certain CAR targets for initial application in NHL, ALL and multiple myeloma.

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We are investigating technology to localize activity of an allogeneic CAR T cell to the tumor microenvironment in an effort to extend specificity and therefore safety of CAR T cells.

We believe this approach may be particularly promising for solid tumor targets that are associated with normal tissue toxicities.

• Next-generation anti-rejection technology:

We are investigating additional ways, beyond our existing anti-CD52 antibody technology, to prevent patient immune rejection of our allogeneic CAR T cells.

We are exploring ways to engineer allogeneic CAR T cells to escape detection from the patient immune system, such as through our research collaboration with Antion Biosciences SA (Antion).

We are also exploring engineering allogeneic CAR T cells with mechanisms to attack certain patient immune cells that would otherwise lead to rejection.

For instance, we are exploring allo-immune defense receptor technology licensed from the Baylor College of Medicine.

This technology is designed to recognize and destroy allo-reactive host immune cells that would otherwise be capable of rejecting the allogeneic CAR T cells, which could provide enhanced persistence of the allogeneic CAR T cells.

We believe this approach may be particularly promising for solid tumor targets that are also expressed on normal tissues.

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

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We have invested resources to optimize our manufacturing process, including the development of improved analytical methods and instrumentation.

We plan to continue to invest in process science, product characterization and manufacturing to continuously improve our production and supply chain capabilities over time.

We plan to continue to invest in process science, product characterization and manufacturing to continuously improve our manufacturing processes, production and supply chain capabilities over time.

Our product candidates are designed and manufactured via a platform comprised of defined unit operations and technologies.

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The CMO that is manufacturing our clinical supply is subject to cGMP requirements, using qualified equipment and materials.

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 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 addition, 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.

We are phasing the build-out of the facility, and completed the build-out of the majority of the facility at the end of 2020.

We initiated cGMP manufacturing of ALLO-501A in 2021.

We plan to use ALLO-501A manufactured at our Newark facility at the commencement of the Phase 2 portion of the ALPHA2 trial.

Introducing ALLO-501A into the ALPHA2 trial will require that we meet certain regulatory conditions, such as establishing comparability with the product candidates manufactured at our CMO, and our inability to meet such conditions would result in investment of additional resources and delay of our clinical trial timeline.

However, we expect to continue to rely on our CMO and may rely on CMOs and other third parties for the manufacturing and processing of our product candidates in the future.

In addition, 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 are phasing the build-out of CF1, and completed the build-out of the majority of the facility at the end of 2020.

We initiated cGMP manufacturing of ALLO-501A in 2021 at CF1 that did not utilize the Alloy process.

After a review of the Phase 1 program and data in 2022, we determined that the Alloy manufacturing process associated with robust clinical performance.

We are currently manufacturing ALLO-501A using the Alloy process at our CMO.

We are currently assessing the product candidates for manufacturing at CF1.

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 CMO, and our inability to meet such conditions would result in investment of additional resources and delay of our clinical trial timeline.

We expect to continue to rely on our CMO and may rely on CMOs and other third parties for the manufacturing and processing of our product candidates in the future.

We also utilize a CMO in the United States for the manufacture and supply of ALLO-647 and we plan to continue to rely on the CMO for future production of ALLO-647.

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On December 14, 2020, we entered into a License Agreement with Allogene Overland Biopharm (CY) Limited, 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.

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), an Exclusive License and Collaboration Agreement with Servier (the Servier Agreement), the Notch Collaboration Agreement, and a License and Collaboration Agreement with Antion.

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, the Notch Collaboration Agreement, and a License and Collaboration Agreement with Antion.

For additional information regarding our significant agreements, see Note 7 to our consolidated financial statements appearing elsewhere in this Annual Report.

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We are actively building our intellectual property portfolio around our product candidates and our discovery programs, based on our own intellectual property as well as licensed intellectual property.

Following the execution of the Pfizer Agreement, we are the owners of, co-owners of, or the licensee of multiple patents and patent applications in the United States and worldwide.

Following the execution of the Pfizer Agreement, we are the owner of, co-owner of, or the licensee of multiple patents and patent applications in the United States and worldwide.

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 and DLL3, and have U.S.

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.

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

With respect to ALLO-501 and ALLO-501A, we have an exclusive license from Servier in the United States to patent rights covering composition of matter and methods of making and use covering ALLO-501 and ALLO-501A.

With respect to ALLO-501 and ALLO-501A, 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 ALLO-501A.

With respect to ALLO-715, ALLO-605 and ALLO-316, we have an exclusive license from Pfizer to patent rights covering ALLO-715, ALLO-605 and ALLO-316 in the United States and in foreign jurisdictions.

These rights include composition of matter protection and methods of making and using ALLO-715, ALLO-605 and ALLO-316.

We also have patent rights to TurboCAR technology solely owned by us, including technology that covers the TurboCAR that is part of ALLO-605.

These rights cover compositions of matter of and methods of making and using ALLO-715, ALLO-605 and ALLO-316.

We also have patent rights to the TurboCAR™ technology solely owned by us, including technology that covers the TurboCAR construct that is part of ALLO-605.

More generally, our patent portfolio and filing strategy is designed to provide multiple layers of protection by pursuing claims directed toward:

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The term of individual patents depends upon the legal term of the patents in the countries in which they are obtained.

In most countries in which we file, the patent term is 20 years from the date of filing of the first non-provisional application to which priority is claimed.

In most countries in which we file, the patent term, generally, is 20 years from the date of filing of the first non-provisional application to which priority is claimed.

In the United States, patent term may be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the United States Patent and Trademark Office in granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier-filed patent.

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Similar provisions are available in Europe and certain other foreign jurisdictions to extend the term of a patent that covers an approved drug.

If successfully developed, our products will compete with novel therapies developed by biopharmaceutical companies, academic research institutions, governmental agencies and public and private research institutions, in addition to standard of care treatments.

Due to the promising therapeutic effect of cell therapies in clinical trials, we anticipate increasing competition from existing and new cell-based products, including products that are both autologous and allogeneic in nature.

Oncology is a highly competitive market for drug development.

If successfully developed, our products will compete with therapies that have been developed or are in development at biopharmaceutical companies, academic research institutions, governmental agencies and public and private research institutions.

We anticipate increasing competition from existing and new cell-based therapies, including products that are both autologous and allogeneic in nature.

We also anticipate competition from other therapeutic modalities, including antibodies, bispecific T cell engagers, antibody drug conjugates, and small molecule therapeutics.

Autologous T cell therapies directed at CD19 have been successfully developed by Novartis, Kite/Gilead and Bristol-Myers Squibb Company (BMS).

Autologous T cell therapies directed at CD19 have been commercialized by Novartis, Kite/Gilead and Bristol-Myers Squibb Company (BMS) and are witnessing increased adoption in the marketplace.

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 R/R large B-cell lymphoma.

In October 2017, Kite/Gilead obtained FDA approval to commercialize Yescarta, for the treatment of adult patients with R/R large B-cell lymphoma.

This was followed by approval of Yescarta for R/R FL in March 2021.

A supplemental BLA for approval of Yescarta in second-line large B-cell lymphoma was submitted in September 2021.

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 (3 rd -line LBCL).

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

This was followed by approval of Yescarta for R/R FL in March 2021 and approval of 2 nd -line LBCL in April 2022.

Kite has also received FDA approval for a second autologous CD19-directed T cell therapy, Tecartus, for use in patients with R/R mantle cell lymphoma and adult patients with R/R B-cell ALL.

In February 2021, BMS obtained FDA approval for its anti-CD19 autologous T cell therapy, Breyanzi (lisocabtagene maraleucel), for the treatment of adults with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least two other types of systemic treatment.

In March 2021, BMS and 2seventy bio, Inc.

received FDA approval of Abecma, an anti-BCMA autologous T cell therapy, for the treatment of adult patients with multiple myeloma who have received at least three prior therapies.

Johnson & Johnson and partner Legend Bio have submitted a BLA for an anti-BCMA autologous T cell therapy, ciltacabtagene autoleucel, for the same indication, and expect an FDA decision in February 2022.

Gilead Sciences, Inc., Gracell Biotechnologies Inc., ImmPACT Bio, USA Inc., Iovance Biotherapeutics, Inc., Legend Biotech Corp., Mustang Bio, Inc., Novartis International AG, Pact Pharma, Inc., TCR² Therapeutics Inc., Tessa Therapeutics, Ltd., Tmunity Therapeutics, Inc, Triumvira Immulogics, and TScan Therapeutics, Inc.

Allogeneic T cell therapies have yet to receive FDA approval though the number of companies developing allogeneic product candidates has expanded greatly in recent years.

This includes ArsenalBio, Atara Biotherapeutics, Inc., Caribou Biosciences, Inc., Celyad S.A., CRISPR Therapeutics AG, Editas Medicine, Inc., Fate Therapeutics, Inc., Gilead Sciences, Inc., Gracell Biotechnologies Inc., Intellia Therapeutics, Inc., Legend Biotech Corp., Poseida Therapeutics, Inc., Precision Biosciences, Inc., Sana Biotechnology, Inc., and Tessa Therapeutics Ltd.

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

Breyanzi’s label was extended to 2 nd -line LBCL in June 2022.

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

In March 2021, BMS and partner 2seventy bio, Inc.

received FDA approval of Abecma, an anti-BCMA autologous T cell therapy, for the treatment of adult patients with multiple myeloma who have received at least four prior therapies.

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, Eureka Therapeutics, Inc., 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, Pact Pharma, Inc., TCR² Therapeutics Inc., Tessa Therapeutics, Ltd., Triumvira Immunologics, and TScan Therapeutics, Inc.

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

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

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 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, 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.

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.

Additionally, companies, such as ADC Therapeutics SA, Amgen Inc., Daiichi Sankyo Company, Limited, Gilead Sciences, Inc., GlaxoSmithKline plc, ImmunoGen, Inc., Seattle Genetics, Inc., Silverback Therapeutics, Inc., and Sutro Biopharma, Inc.

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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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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 approval.

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.

The FDA will attempt to direct additional resources to the evaluation of an application for a

new product designated for priority review in an effort to facilitate the review.

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.

The FDA will attempt to direct additional resources to the evaluation of an application for a new product designated for priority review in an effort to facilitate the review.

Additionally, a product may be eligible for accelerated approval.

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In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

Regenerative Medicine Advanced Therapy (RMAT) designation was established by FDA in 2017 to facilitate an efficient development program for, and expedite review of, any drug that meets the following criteria:

Regenerative Medicine Advanced Therapy (RMAT) designation was established by FDA to facilitate an efficient development program for, and expedite review of, any drug that meets the following criteria:

(1) it qualifies as a RMAT, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, with limited exceptions;

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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.

In 2021, the FDA granted fast track designation status to ALLO-501A for the treatment of adult patients with R/R DLBCL and to ALLO-605 for the treatment of adult patients with R/R multiple myeloma.

The FDA also granted RMAT designation to ALLO-715 for the treatment of adult patients with R/R multiple myeloma after three or more prior lines of therapies.

We have received RMAT designation for ALLO-715 and ALLO-501A and fast track designation for ALLO-605 and ALLO-316.

Post-Approval Requirements

Any products for which we receive FDA approvals are subject to continuing regulation by the FDA, including, among other things, record-keeping requirements, reporting of adverse experiences with the product, providing the FDA with updated safety and efficacy information, product sampling and distribution requirements, and complying with FDA promotion and advertising requirements, which include, among others, standards for direct-to-consumer advertising, restrictions on promoting products for uses or in patient populations that are not described in the product’s approved uses (known as “off-label use”), limitations on industry-sponsored scientific and educational activities, and requirements for promotional activities involving the internet.

Although a physician may prescribe a legally available product for an off-label use, if the physicians deems such product to be appropriate in his/her professional medical judgment, a manufacturer may not market or promote off-label uses.

Although a physician may prescribe a legally available product for an off-label use, if the physician deems such product to be appropriate in his/her professional medical judgment, a manufacturer may not market or promote off-label uses.

However, it is permissible to share in certain circumstances truthful and not misleading information that is consistent with the product’s approved labeling.

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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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For example, our business practices, including any of our research and future sales, marketing and scientific/educational grant programs may be required to comply with the anti-fraud and abuse provisions of the Social Security Act, the false claims laws, the patient data privacy and security provisions of the Health Insurance Portability and Accountability Act (HIPAA), transparency requirements, and similar state, local and foreign laws, each as amended.

The federal Anti-Kickback Statute prohibits, among other things, any person or entity, from knowingly and willfully offering, paying, soliciting or receiving any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce or in return for purchasing, leasing, ordering or arranging for the purchase, lease or order of any item, good, facility or service

reimbursable under Medicare, Medicaid or other federal healthcare programs.

The term remuneration has been interpreted broadly to include anything of value.

The term remuneration has been interpreted

broadly to include anything of value.

The federal Anti-Kickback Statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on one hand and prescribers, purchasers, formulary managers, and other individuals and entities on the other.

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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.

Additionally, the federal Physician Payments Sunshine Act within the Affordable Care Act, and its implementing regulations, require that certain manufacturers of drugs, devices, biological and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program (with certain exceptions) annually report information to CMS related to certain payments or other transfers of value made or distributed to physicians (defined to include doctors,

dentists, optometrists, podiatrists and chiropractors), other healthcare professionals (such as physicians assistants and nurse practitioners) and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, physicians and teaching hospitals and certain ownership and investment interests held by physicians and their immediate family members.

practitioners) and teaching hospitals, or to entities or individuals at the request of, or designated on behalf of, physicians and teaching hospitals and certain ownership and investment interests held by physicians and their immediate family members.

In order to distribute products commercially, we must comply with state laws that require the registration of manufacturers and wholesale distributors of drug and biological products in a state, including, in certain states, manufacturers and distributors who ship products into the state even if such manufacturers or distributors have no place of business within the state.

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Coverage policies and third-party reimbursement rates may change at any time.

Even if favorable coverage and reimbursement

status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.

Healthcare Reform

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• expanded eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals and added new mandatory eligibility categories for individuals with income at or below 133% of the federal poverty level, thereby potentially increasing manufacturers’ Medicaid rebate liability;

• expanded of the entities eligible for discounts under the 340B Drug Discount Program;

• expanded the entities eligible for discounts under the 340B Drug Discount Program;

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

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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.

Further, 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 June 17, 2021, the U.S.

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

Thus, the Affordable Care Act will remain in effect in its current form.

Further, prior to the U.S.

Supreme Court ruling, on January 28, 2021, President Biden issued an executive order to initiate a special enrollment period for purposes of obtaining health insurance coverage through the Affordable Care Act marketplace.

The executive order also instructs certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the Affordable Care Act.

It is unclear how such challenges and the healthcare reform measures of the Biden administration will impact the Affordable Care Act.

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.

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

It is possible that the Affordable Care Act will be subject to judicial or Congressional challenges in the future.

It is unclear how such challenges and any additional healthcare reform measures will impact the Affordable Care Act.

Further legislation or regulation could be passed that could harm our business, financial condition and results of operations.

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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 through 2031 unless additional Congressional action is taken.

However, COVID-19 relief support legislation suspended the 2% Medicare sequester from May 1, 2020 through March 31, 2022.

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 2031 unless additional Congressional action is taken.

Under current legislation, the actual reduction in Medicare payments will vary from 1% in 2022 to up to 4% in the final fiscal year of this sequester.

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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.

For example, on July 24, 2020 and September 13, 2020, the Trump administration announced several executive orders related to prescription drug pricing that attempt to implement several of the administration’s proposals.

The FDA also released a final rule and guidance in September 2020, implementing a portion of the importation executive order providing pathways for states to build and submit importation plans for drugs from Canada.

Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

The implementation of the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing litigation.

The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which have also been delayed pending review by the Biden administration until January 1, 2023.

On November 20, 2020, CMS issued an interim final rule implementing President Trump’s Most Favored Nation executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries.

As a result of litigation challenging the Most Favored Nation model, on December 27, 2021, CMS published a final rule that rescinded the Most Favored Nation model interim final rule.

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

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.

No legislation or administrative actions have been finalized to implement these principles.

In addition, Congress is considering drug pricing as part of other reform initiatives.

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, although they may be subject to legal challenges.

Additionally, the Biden administration released an additional executive order on October 14, 2022, directing HHS to report on how the Center for Medicare and Medicaid Innovation can be further leveraged to test new models for lowering drug costs for Medicare and Medicaid beneficiaries.

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.

We anticipate that these and other healthcare reform efforts will continue to result in additional downward pressure on coverage and the price that we receive for any approved product, and could seriously harm our business.

Any reduction in reimbursement from Medicare and other government programs may result in a similar reduction in payments from private

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

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

Such reforms could have an adverse effect on anticipated revenue from product candidates that we may successfully develop and for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop product candidates.

Further, it is possible that additional governmental action will be taken in response to the COVID-19 pandemic.

The Foreign Corrupt Practices Act

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individual or business from paying, offering, or authorizing payment or offering of anything of value, directly or indirectly, to any foreign official, political party or candidate for the purpose of influencing any act or decision of the foreign entity in order to assist the individual or business in obtaining or retaining business.

The FCPA also obligates companies whose securities are listed in the United States to comply with accounting provisions requiring the company to maintain books and records that accurately and fairly reflect all transactions of the corporation, including international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

international subsidiaries, and to devise and maintain an adequate system of internal accounting controls for international operations.

Additional Regulation

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European Union General Data Protection Regulation

In addition to EU regulations related to the approval and commercialization of our products, we may be subject to the EU’s General Data Protection Regulation (GDPR).

The GDPR imposes stringent requirements for controllers and processors of personal data of persons in the EU, including, for example, more robust disclosures to individuals and a strengthened individual data rights regime, shortened timelines for data breach notifications, limitations on retention of information, increased requirements pertaining to special categories of data, such as health data, and additional obligations when we contract with third-party processors in connection with the processing of the personal data.

The GDPR also imposes strict rules on the transfer of personal data out of the European Union to the United States and other third countries.

In addition, the GDPR provides that EU member states may make their own further laws and regulations limiting the processing of personal data, including genetic, biometric or health data.

The GDPR applies extraterritorially, and we may be subject to the GDPR because of our data processing activities that involve the personal data of individuals located in the European Union, such as in connection with our EU clinical trials.

Failure to comply with the requirements of the GDPR and the applicable national data protection laws of the EU member states may result in fines of up to €20,000,000 or up to 4% of the total worldwide annual turnover of the preceding financial year, whichever is higher, and other administrative penalties.

GDPR regulations may impose additional responsibility and liability in relation to the personal data that we process and we may be required to put in place additional mechanisms to ensure compliance with the new data protection rules.

In addition to EU regulations related to the approval and commercialization of our products, we may be subject to the EU’s General Data Protection Regulation (EU GDPR).

The EU GDPR imposes stringent requirements for controllers and processors of personal data of persons in the EU, including, for example, more robust disclosures to individuals and a strengthened individual data rights regime, shortened timelines for data breach notifications, limitations on retention of information, increased requirements pertaining to special categories of data, such as health data, and additional obligations when we contract with third-party processors in connection with the processing of the personal data.

The EU GDPR also imposes strict rules on the transfer of personal data out of the European Union to the United States and other third countries.

In addition, the EU GDPR provides that EU member states may make their own further laws and regulations limiting the processing of personal data, including genetic, biometric or health data.

The EU GDPR applies extraterritorially, and we may be subject to the EU GDPR because of our data processing activities that involve the personal data of individuals located in the European Union, such as in connection with our EU clinical trials.

Failure to comply with the requirements of the EU GDPR and the applicable national data protection laws of the EU member states may result in fines of up to €20,000,000 or up to 4% of the total worldwide annual turnover of the preceding

financial year, whichever is higher, private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests, and other administrative penalties.

The EU GDPR regulations may impose additional responsibility and liability in relation to the personal data that we process and we may be required to put in place additional mechanisms to ensure compliance with the new data protection rules.

California Consumer Privacy Act

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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, will expand the CCPA.

The CPRA will, among other things, give California residents the ability to limit use of certain sensitive personal data, establish restrictions on personal data retention, expand the types of data breaches that are subject to the CCPA’s private right of action, and establish a new California Privacy Protection Agency to implement and enforce the new law.

In addition, the California Privacy Rights Act of 2020 (CPRA), effective January 1, 2023, expands the CCPA.

The CPRA, among other things, gives California residents the ability to limit use of certain sensitive personal data, establishes restrictions on personal data retention, expands the types of data breaches that are subject to the CCPA’s private right of action, and establishes a new California Privacy Protection Agency to implement and enforce the new law.

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.

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degrees, and 279 are engaged in research, development and technical operations.

Substantially all of our employees are located in South San Francisco and Newark, California.

Most of our employees are located in South San Francisco and Newark, California.

Our employees are not represented by labor unions or covered by collective bargaining agreements.

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

Given the COVID-19 pandemic, we have also focused on COVID-19 safety measures and new ways of generating employee engagement.

We have also strived to create a safe working environment and have increased onsite presence since the emergence of COVID-19.

One Allogene Culture

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In addition, as of February 1, 2023, 67% of all employees were self-reportedly ethnic or racial minorities in the U.S., with 52% Asian, 1% Black or African American, 7% Hispanic or Latino and 7% of other minority groups or two or more races.

Of our Director-level and above employees, 39% were self-reportedly ethnic or racial minorities in the U.S., with 33% Asian, 2% Hispanic or Latino and 4% 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 37% Asian, 2% Black or African American, 5% Hispanic or Latino and 4% of other minority groups or two or more races.

Although we are proud of our efforts and metrics to date, we are focused on broadening our outreach and increasing opportunities to underrepresented minorities, including increased recruitment efforts in minority communities by posting our open positions on top job boards for diversity hiring, participating in diversity focused career fairs and hosting science, technology, engineering, and mathematics (STEM)-based outreach in underserved communities at the elementary, junior high and high school level.

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The DEI Committee formalized a DEI mission statement and also advanced a DEI policy that sets forth our commitment to the importance of DEI 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 DEI policy, all employees are also required to attend and complete annual diversity awareness training to enhance their knowledge to fulfill this responsibility.

The DEI Committee and DEI Advisory Board

continually work to identify gaps, 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.

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

The DEI Committee and DEI Advisory Board continually work to identify gaps, 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.

We believe in equal pay for equal work.

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

Our voluntary attrition rate increased in 2021 to 22% and we believe we will continue to face significant competition for life science talent.

COVID-19 Employee Safety and Engagement

In March 2020 and in response to the spread of COVID-19 and state and local orders, we limited the number of staff working at our facilities.

We also established an internal COVID-19 task force to ensure timely communication and decision-making in response to COVID-19.

For laboratory, manufacturing and support staff onsite, we implemented new safety protocols, such as facial covering and temperature check requirements.

We intend to continue to examine our protocols as the pandemic and health guidance evolves.

While our voluntary attrition rate decreased in 2022 to less than 15%, we believe we will continue to face significant competition for life science talent.

Employee Safety

One key aspect of our One Allogene culture is the principle that “We Aim for Excellence and Give it Our All,” and that includes prioritizing safety.

Ingrained in that concept is the tenet to follow all health and safety policies and procedures and prioritize the safety of our team.

To maintain a safe and healthy workplace, we have a comprehensive Environment, Health and Safety program that focuses on key risk mitigation programs that identify, assess, and correct hazards.

We also have a task-based safety training program that is designed for staff to be assigned the appropriate training to understand how to safely perform their duties.

Corporate Information

6 unchanged sentences

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