What changed in this filing

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Item 1. Business

2021-02-25 compared with 2020-02-27 · 477 added, 289 removed, 620 unchanged (55% of the section changed)

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Our allogeneic T cell development strategy has four key pillars:

(1) developing product candidates to minimize the risk of graft-versus-host disease (GvHD), a condition where allogeneic T cells can recognize the patient’s normal tissue as foreign and cause damage, (2) creating a window of persistence that may enable allogeneic T cells to expand in patients, (3) building a leading manufacturing platform and (4) leveraging next generation technologies to improve the functionality of allogeneic CAR T cells.

(1) engineering product candidates to minimize the risk of graft-versus-host disease (GvHD), a condition where allogeneic T cells can recognize the patient’s normal tissue as foreign and cause damage, (2) creating a window of persistence that may enable allogeneic T cells to expand and eradicate cancer cells in patients, (3) building a leading manufacturing platform to enable consistent and high quality production and (4) leveraging next generation technologies to improve the functionality of allogeneic CAR T cells.

We use Cellectis, S.A.

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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.

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 building 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 build our own cell therapy manufacturing facility in Newark, California, and we expect to commence manufacturing at our facility in 2021.

In February 2019, we entered into a lease to build our own cell therapy manufacturing facility in Newark, California, and we expect to commence 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.

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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.

Several of our most advanced product candidates, including UCART19, 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.

We are also developing engineered allogeneic CAR T cell product candidates for multiple myeloma, other blood cancers and solid tumors.

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.

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.

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

2 Servier will hold ex-US commercial rights.

Servier is the sponsor of the UCART19 trials.

3 Allogene is the sponsor of the ALLO-501 trial and plans to sponsor a trial for ALLO-501A.

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

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.

Our lead product candidates include:

Our collaboration partner, Servier, is sponsoring two Phase 1 clinical trials of UCART19 in patients with R/R ALL, one for adult patients (the CALM trial) and one for pediatric patients (the PALL trial).

In December 2018, interim results from 21 patients in the CALM and PALL clinical trials were presented at the 60th American Society of Hematology (ASH) Annual Meeting.

As of October 23, 2018, 67% (14/21) of patients achieved complete remission (CR) or complete remission with incomplete blood recovery (CRi).

Eighty-two percent (14/17) of patients who received a lymphodepletion regimen consisting of fludarabine, cyclophosphamide and an anti-CD52 monoclonal antibody (FCA) achieved a CR/CRi.

In the four patients who received fludarabine and cyclophosphamide (FC) only, there was no evidence of UCART19 cell expansion and no responses were observed.

We believe the interim data of UCART19 suggest an anti-CD52 antibody is an important addition to the lymphodepletion regimen for allogeneic CAR T cell expansion, and we are progressing the development of our own anti-CD52 antibody, ALLO-647, as described below.

The most common adverse events were related to cytokine release syndrome (CRS) and were generally manageable.

Two mild (Grade 1) GvHD cases in the skin were observed and resolved.

Subject to the continued advancement of the Phase 1 trials, we expect UCART19 to be advanced to potential registrational trials in 2021.

See “—Product Pipeline and Development Strategy—UCART19—Pooled CALM and PALL Clinical Findings—Interim Safety” for more information regarding adverse events.

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.

This includes R/R large B-cell lymphoma and R/R follicular lymphoma (FL).

In January 2019, the FDA cleared our investigational new drug application (IND) for the ALPHA trial, and we initiated the trial in the second quarter of 2019.

We expect to report initial data from the trial in the second quarter of 2020.

We plan to use the clinical data from ALLO-501 to accelerate the development of the second-generation version of ALLO-501, known as ALLO-501A.

We have removed rituximab recognition domains in ALLO-501A, which we believe will potentially facilitate treatment of more patients, as rituximab is a typical part of a treatment regimen for a patient with NHL.

In December 2019, the FDA cleared our IND to initiate a Phase 1/2 clinical trial for ALLO-501A (the ALPHA2 trial) and we plan to initiate the trial in the second quarter of 2020, subject to completing the manufacturing of ALLO-501A.

In May 2020, initial results from the ALPHA trial were presented at the American Society of Clinical Oncology (ASCO) annual meeting.

See “—Product Pipeline and Development Strategy—Anti-CD19 Development Program—Initial Phase 1 Results from the ALPHA Trial” for information regarding the initial data results.

We are continuing the ALPHA trial to further explore ALLO-501 and lymphodepletion dose and schedule.

We plan to report updated clinical data from the ALPHA trial in the second quarter of 2021.

We have removed rituximab recognition domains in our second-generation version of ALLO-501, known as ALLO-501A, which we believe will potentially facilitate treatment of more patients, as rituximab is a typical part of a treatment regimen for a patient with NHL.

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.

We plan to report initial clinical data from the ALPHA2 trial in the second quarter of 2021.

Subject to data, we plan to proceed to the Phase 2 portion of the trial by the end of 2021.

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.

In May 2019, the FDA cleared our IND for the UNIVERSAL trial, and we initiated the trial in the third quarter of 2019.

We expect to report initial data from the trial in the fourth quarter of 2020.

In addition, in January 2020, we entered into a clinical trial collaboration agreement with SpringWorks Therapeutics, Inc.

(SpringWorks) to evaluate ALLO-715 in combination with SpringWorks’ investigational gamma secretase inhibitor (GSI), nirogacestat, in patients with R/R multiple myeloma.

We plan to initiate this combination trial in the second half of 2020, subject to regulatory clearance.

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

In December 2020, initial results from the UNIVERSAL trial were presented at the American Society of Hematology (ASH) annual meeting.

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

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

We plan to report updated clinical data from the UNIVERSAL trial in the fourth quarter of 2021.

• ALLO-715 plus nirogacestat.

We recently initiated an expansion of the UNIVERSAL trial to assess ALLO-715 in combination with SpringWorks Therapeutics, Inc.’s investigational gamma secretase inhibitor, nirogacestat.

We believe nirogacestat has the potential to increase the cell surface density of BCMA and reduce levels of soluble BCMA, thereby enhancing the activity of ALLO-715.

We are advancing ALLO-605, an allogeneic CAR T cell product candidate targeting BCMA and our first product candidate to incorporate our TurboCAR technology, for multiple myeloma.

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 prevent and delay exhaustion of the cells in preclinical models.

We expect to submit an investigational new drug application (IND) in the first half of 2021 to initiate a Phase 1 clinical trial of ALLO-605.

Following the clearance of an IND in December 2020, we plan to initiate 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 in the first quarter of 2021.

We also plan to investigate the use of ALLO-316 for a second indication in R/R acute myeloid leukemia (AML).

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 the ALPHA trial and UNIVERSAL trial, and plan to utilize ALLO-647 in the ALPHA2 trial.

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

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 UCART19, ALLO-501 and ALLO-501A, and we hold the commercial rights to these product candidates in the United States.

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 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 under our collaboration with Servier.

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.

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Autologous anti-CD19 CAR T cell therapies, such as Kymriah and Yescarta, have emerged as potentially curative therapies for B-cell lymphomas and leukemias.

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, including NHL and ALL.

We plan to support Servier in advancing the CALM and PALL trials in R/R ALL.

We also expect to report initial data from the ALPHA trial in R/R NHL in the second quarter of 2020, and build on this data by rapidly advancing the clinical development of ALLO-501A.

We believe having the first anti-CD19 allogeneic CAR T cell product candidate in the clinic gives us a leadership advantage in efforts to obtain approval of and commercialize anti-CD19 allogeneic CAR T cell product candidates in B-cell lymphoma and leukemia indications.

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 believe our efforts to advance ALLO-501A and, subject to our clinical data, proceed to the Phase 2

portion of the ALPHA2 trial by the end of 2021 would give us a leadership advantage to obtain the potential first approval of an anti-CD19 allogeneic CAR T cell product candidate.

• Expand our leadership position within hematologic indications .

In addition to UCART19 and ALLO-501A, we plan to advance our near-term pipeline against additional hematological targets where there remains a high unmet need.

For example, we are developing ALLO-715, an allogeneic CAR T cell product candidate targeting BCMA.

We believe BCMA is a promising target, as early results from clinical trials of third-party autologous CAR T cell therapeutic candidates targeting BCMA have been compelling.

Our Phase 1 clinical trial of ALLO-715 for the treatment of patients with R/R multiple myeloma is the first to study an allogeneic CAR T therapy targeting BCMA and we plan to report initial data from the trial in the fourth quarter of 2020.

In addition, we plan to initiate a combination trial of ALLO-715 with SpringWorks’ nirogacestat, in patients with R/R multiple myeloma in the second half of 2020, subject to regulatory clearance.

We believe nirogacestat has the potential to increase the cell surface density of BCMA and reduce levels of soluble BCMA, thereby enhancing the activity of ALLO-715.

We also plan to develop additional allogeneic T cell product candidates targeting other antigens found on hematologic malignancies, including ALLO-316 targeting CD70 and ALLO-819 targeting FLT3, each for the treatment of acute myeloid leukemia (AML).

In addition to ALLO-501A, we plan to advance our near-term pipeline against additional hematologic targets where there remains a high unmet need.

For example, we have a three-part strategy to target BCMA for the treatment of patients with R/R multiple myeloma.

We believe BCMA is a promising target, as results from clinical trials of third-party autologous CAR T cell therapeutic candidates targeting BCMA have produced encouraging data.

The first part of our strategy is to continue to advance the UNIVERSAL trial of ALLO-715, which is the first trial of an allogeneic CAR T therapy targeting BCMA.

We plan to report updated data from the UNIVERSAL trial in the fourth quarter of 2021.

Second, we are utilizing the UNIVERSAL trial to assess ALLO-715 in combination with nirogacestat.

Third, we expect to submit an IND in the first half of 2021 to initiate a Phase 1 clinical trial of ALLO-605, our first TurboCAR candidate.

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

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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 plan to phase the build-out of the facility, and expect to complete the build-out of the majority of the facility in the second half of 2020 and initiate manufacturing under current good manufacturing practices (cGMP) in 2021.

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 plan to initiate 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 product candidates.

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

We have a broad portfolio of solid tumor targets, including CD70 for the treatment of renal cell cancer and DLL3 for the treatment of small cell lung cancer and other aggressive neuroendocrine tumors.

We 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 developing TurboCARs, which include a CAR T cell-specific cytokine signal designed to augment the potency and durability of allogeneic T cells.

• 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 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 expect to advance a TurboCAR product candidate, ALLO-605, to the clinic this year and 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.

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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 T cell therapies for the benefit of patients.

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.

• Accelerate the development of our product candidates across geographies .

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

Subject to our clinical progress in the United States, we plan to initiate clinical trials in the European Union and United Kingdom.

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.

Allogeneic T Cell Therapy

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Engineered T Cell Therapies

Engineered T cell therapy is a type of immunotherapy treatment whereby human T cells are removed from the body and engineered to express CARs which, when infused into a patient, may recognize and destroy cancer cells in a targeted manner.

Engineered T cell therapy is a type of immunotherapy treatment whereby human T cells are removed from the body and engineered to express CARs which, when infused into a patient, may allow the recognition and destruction of cancer cells in a targeted manner.

Chimeric Antigen Receptors (CARs)

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

The CAR in UCART19, ALLO-501, ALLO-501A and ALLO-715 is comprised of a single chain protein that contains the following elements:

The CAR in our product candidates is comprised of a single chain protein that contains the following elements:

• Target Binding Domain:

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In addition to the domains described above, ALLO-715 possesses two rituximab-recognition domains between the scFv and the hinge which allow it to be recognized and eliminated by rituximab.

UCART19 and ALLO-501 possess rituximab recognition domains in a separate polypeptide termed RQR8 that is co-expressed with the CAR.

ALLO-501 possesses rituximab recognition domains in a separate polypeptide termed RQR8 that is co-expressed with the CAR.

The figure below shows the constructs that support our lead programs:

UCART19, ALLO-501, ALLO-501A and ALLO-715.

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

ALLO-501, ALLO-501A and ALLO-715.

Allogeneic T Cell Therapies:

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autologous and allogeneic.

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

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.

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

In addition, certain patients being treated with autologous product candidates have required bridging therapy as they wait for the manufacture of their T cells.

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

• Variable Potency .

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The complex logistics add significant cost to the process and limit the ability to scale.

Additionally, the collection of T cells through leukapheresis from each individual patient results in a time consuming

and costly step in the autologous process.

Additionally, the collection of T cells through leukapheresis from each individual patient results in a time consuming and costly step in the autologous process.

In part due to these logistics, autologous treatment is currently only available at select centers.

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Because our allogeneic product candidates are designed to be frozen and available off-the-shelf, they could potentially be readily shipped and administered to patients.

We believe having an inventory of off-the-shelf allogeneic T cell products can also facilitate delivering multiple product doses to a patient over time as well as enable treatment with multiple different engineered allogeneic T cell products directed to different cancer targets in a patient.

We believe having an inventory of off-the-shelf allogeneic T cell products can also facilitate delivering multiple product doses to a patient over time.

• Speed to Patient .

Many patients with aggressive cancer or rapidly progressing cancer that is refractory to existing therapies may not have multiple weeks to wait for autologous T cell treatment.

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

This would represent a significant reduction in patient wait time, potentially allowing the treatment of patients who are too sick to wait for the autologous therapy, and could improve patient outcomes.

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

This would represent a significant reduction in patient wait time, potentially obviating the need for any bridging therapy and allowing the treatment of patients who are too sick to wait for the autologous therapy, and could improve patient outcomes.

• Enhanced Cell Consistency and Potency .

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The TALE DNA-binding domain can be tailored to specifically recognize a unique DNA sequence.

These fusion proteins serve as readily targetable “DNA scissors” for genome engineering applications that enable us to perform targeted genome modifications such as sequence insertion, deletion, repair and replacement in living cells.

These fusion proteins serve as readily targetable “DNA scissors” for genome engineering applications that can enable targeted genome modifications.

Electroporation allows TALEN mRNA to enter into the cell, where it is translated into a nuclease that can cut DNA and inactivate specific target genes.

Inactivation of genes, such as TCRα and CD52, which is performed for UCART19, ALLO-501, ALLO-501A, and ALLO-715, is intended to reduce the risk of GvHD and allow the allogeneic T cells to expand and persist in patients.

Inactivation of genes, such as TCRα and CD52, is intended to reduce the risk of GvHD and allow the allogeneic T cells to expand and persist in patients.

We believe the inactivation of other target genes using the TALEN technology can be incorporated into future product candidates, with the goal of enhancing T cell function, including increasing potency against solid tumors.

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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 the ALPHA trial and UNIVERSAL trial, and plan to utilize ALLO-647 in the ALPHA2 trial.

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

Purification, Formulation, and Storage

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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 can completely inactivate the target genes.

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

After overnight recovery, the cells are formulated in a cryopreservation media and filled into closed, stoppered vials prior to controlled-rate freezing and long-term storage in the vapor phase of liquid nitrogen.

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Each product candidate targets a selected antigen expressed on tumor cells and bears specific engineered attributes.

In the near term, we are progressing multiple product candidates directed at promising targets for blood cancers, including ALL, NHL, multiple myeloma and AML.

We are also conducting earlier-stage research programs focused on targets associated with solid tumors, such as renal cell carcinoma, small cell lung cancer and other common epithelial cancers.

Our product pipeline is represented in the diagram below:

1 Servier holds ex-US commercial rights.

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

2 Servier will hold ex-US commercial rights.

Servier is the sponsor of the UCART19 trials.

3 Allogene is the sponsor of the ALLO-501 trial and plans to sponsor a trial for ALLO-501A.

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

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

In addition to the allogeneic CAR T cell product candidates we are developing for the treatment of blood cancers and solid tumors, we are developing an anti-CD52 monoclonal antibody, ALLO-647, which is designed to be used prior to infusing our other product candidates as part of the lymphodepletion regimen.

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

In addition to our development of allogeneic CAR T cell product candidates, we are developing an anti-CD52 monoclonal antibody, ALLO-647, which is designed to be used prior to infusing our other product candidates as part of the lymphodepletion regimen.

As illustrated below, we believe ALLO-647 can reduce the likelihood of a patient’s immune system from 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, in partnership with Servier, are developing UCART19 to be a potential first-in-class allogeneic CAR T cell product candidate for the treatment of pediatric and adult patients with R/R CD19 positive B-cell ALL.

There are currently two ongoing Phase 1 clinical trials in adult and pediatric R/R ALL.

Servier is the sponsor of the UCART19 clinical trials and is also responsible for manufacturing UCART19.

UCART19 targets CD19, an antigen expressed on the surface of B cells, including malignant B cells.

In addition to these indications, CD19 targeting CAR T therapies have shown preliminary efficacy in chronic lymphocytic leukemia, mantle cell lymphoma and low-grade NHLs, such as FL or marginal zone lymphoma.

UCART19 is 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.

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

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

The figure below depicts the construct of UCART19.

Target Indication:

Acute Lymphoblastic Leukemia (ALL)

ALL is characterized by the proliferation of immature lymphocytes in the bone marrow.

Approximately 6,150 new cases and 1,520 deaths in the United States are estimated in 2020, according to the American Cancer Society.

Approximately 80% of cases of ALL are B-cell ALL, which we plan to address with UCART19.

The risk for developing ALL is highest in children younger than five years of age.

From age five until the mid-20s, the risk declines slowly and begins to steadily rise again after age 50.

Overall, about 40% of all cases of ALL are in adults.

Though most cases occur in children, approximately 80% of deaths from ALL occur in adults.

Over the past four decades pediatric cure rates have reached greater than 80% in developed countries.

This progress can be attributed, in part, to a deeper understanding of the molecular genetics and pathogenesis of the disease, advances in combination chemotherapy, monitoring of minimal residual disease, and use of tyrosine kinase inhibitors for Philadelphia chromosome–positive ALL.

Allogeneic stem-cell transplant (allo-SCT) offers the potential for cure in some individuals, however, the option is available only to approximately a third of patients due to the lack of compatible stem cell source, general health, or the high risk of complications.

Furthermore, allo-SCT carries a high rate of treatment-related mortality which can occur in approximately 20-30% of patients undergoing allo-SCT.

In patients with R/R ALL after two or more lines of therapy, the median disease-free survival is less than six months.

The five-year overall survival in adults over the age of 60 is approximately 20%, highlighting the high unmet need despite the recent advances in the treatment of ALL.

Clinical Data

UCART19 is being studied in two ongoing Phase 1 clinical trials, CALM and PALL, sponsored and conducted by Servier, our collaboration partner.

Initiated in 2016, CALM is an ongoing Phase 1, open-label, dose-escalation clinical trial in adult patients with R/R ALL to evaluate safety, anti-leukemic activity, and determine the maximum tolerated dose.

Post-therapy allo-SCT was allowed at the discretion of the investigator.

Initiated in 2016, PALL is an ongoing Phase 1, open-label, clinical trial in pediatric R/R ALL patients to evaluate safety and anti-leukemic activity.

Prior to the initiation of CALM and PALL, UCART19 was administered to three patients with CD19 positive B-cell ALL (two children and one adult) under a compassionate use license granted by the Medicines and Healthcare Products Regulatory Agency in the United Kingdom.

The patients had previously failed multiple lines of prior treatment.

UCART19 for these patients was manufactured at an academic site, the University College London.

The two pediatric patients achieved a CR and received allo-SCT, and the one adult died within the first month following UCART19 infusion due to disease progression.

Pooled CALM and PALL Interim Clinical Findings

In December 2018, interim results from 21 patients in the CALM and PALL clinical trials were presented at the 60th ASH Annual Meeting.

As of the October 23, 2018 data cutoff, 21 patients enrolled had been treated in the CALM and PALL clinical trials.

In the CALM trial, six patients were treated at the first dose level of 6 × 10 6 total cells (approximately 10 5 cells per kilogram) and six patients were treated at the second dose level with 8 × 10 7 total cells (approximately 10 6 cells per kilogram).

Two patients were treated at the third dose level of 1.8 to 2.4 × 10 8 total cells.

In the PALL trial, all seven of the patients enrolled had been treated at a weight-banded cell dose equivalent to 1.1 to 2.3 × 10 6 cells/kg.

Patient characteristics are presented below.

Median age in yrs (range) 22 (0.8-62)

No of prior treatment lines

Median (range) 4 (1-6)

Previous allo-SCT 13

Time of relapse following previous allo-SCT

Bone marrow blasts prior to lymphodepletion

Median (range) 8% (0-96)

Interim Safety

The table below summarizes the adverse events by grade related to UCART19 infusion as well as those related to the lymphodepletion regimen as of October 23, 2018.

Grade 1 represents mild toxicity, Grade 2 represents moderate toxicity, Grade 3 represents severe toxicity and Grade 4 represents life threatening toxicity.

Grade 5 toxicity represents toxicity resulting in death.

n(%) All Grades

AEs related to UCART19

Cytokine release syndrome 4 (19.0) 12 (57.1) 2 (9.5) 1*(4.8) — 19 (90.5)

Neurotoxicity events 7 (33.3) 1 (4.8) — — — 8 (38.1)

Acute skin graft-versus-host disease(1) 2 (9.5) — — — — 2 (9.5)

AEs related to lymphodepletion and/or UCART19

Prolonged cytopenia(2) — — — 6+ (28.5) — 6 (28.5)

Viral infections(3) 1 (4.8) 2 (9.5) 4 (19.0) 1 (4.8) — 8 (38.1)

Neutropenic sepsis — — — 1 (4.8) 1* (4.8) 2 (9.5)

Febrile neutropenia / septic shock — — — — 1 (4.8) 1 (4.8)

Pulmonary hemorrhage — — — — 1+ (4.8) 1 (4.8)

_______________________

(1) GvHD confirmed by biopsy in 1 out of 2 cases.

(2) Persistent Grade 4 neutropenia and/or thrombocytopenia beyond day 42 post UCART19 infusion, except if >5% bone marrow blast.

(3) Viral infections:

CMV, ADV, BK virus, metapneumovirus.

* One dose limiting toxicity at Dose Level 1:

Grade 4 CRS associated with Grade 5 neutropenic sepsis (death at D15 post-infusion).

+ One dose limiting toxicity at Dose Level 2:

Grade 4 prolonged cytopenia associated with infection and Grade 5 pulmonary hemorrhage (death at D82 post-infusion).

The most common UCART19 related adverse event was CRS, reported in 19 patients.

Grade 3 or 4 CRS was observed in three patients.

Six patients developed prolonged cytopenia, defined as persistent Grade 4 neutropenia and/or thombocytopenia beyond day 42 after UCART19 infusion.

Seven patients experienced mild, or Grade 1, neurotoxicity events and one patient experienced Grade 2 neurotoxicity events.

Viral infections were attributed to lymphodepletion and/or UCART19.

Two patients experienced Grade 1 GvHD adverse event of the skin, which resolved with steroids.

As previously presented, there were two treatment-related deaths in the CALM study, one at day 15 post infusion as a result of Grade 4 CRS associated with Grade 5 neutropenic sepsis and one at day 82 post infusion with Grade 5 pulmonary hemorrhage in the post allogeneic stem-cell transplant setting.

Since the data cut-off, one additional CALM patient was treated

at the third dose level and died of a treatment-related multiple organ dysfunction syndrome.

Grade 5 adverse events have been reported in other autologous anti-CD19 CAR T cell therapy trials in part due to advanced stage of disease and accompanying confounding conditions.

Of the 21 evaluable patients, thirteen deaths have been reported that were not attributed to UCART19, but due to progressive disease or allo-SCT related complications.

Interim Efficacy

As of October 2018, 67% (14/21) of patients achieved a CR/CRi.

Eighty-two percent (14/17) of patients who received a lymphodepletion regimen consisting of fludarabine, cyclophosphamide and an anti-CD52 monoclonal antibody (FCA) achieved a CR/CRi.

In the four patients who received fludarabine and cyclophosphamide (FC) only, there was no evidence of UCART19 cell expansion and no response.

Seventy-one percent (10/14) of patients achieved MRD- CR.

Three patients received a second dose of UCART19, two under compassionate use (as a deviation from the clinical trial protocol) and one under amended protocol, and two achieved cell expansion and MRD- CR.

MRD- CR occurs when a patient achieves a CR and there is no evidence of ALL cells in the marrow when using sensitive tests such as polymerase chain reaction or flow cytometry.

CR or CRi rates are the typical regulatory standard, but studies in both children and adults with ALL have demonstrated a strong correlation between minimal residual disease (MRD+) and risks for relapse.

We believe these data suggest an anti-CD52 antibody is an important addition to the lymphodepletion regimen for allogeneic CAR T cell expansion.

We therefore believe that an anti-CD52 antibody is important to the success of our allogeneic CAR T platform.

Going forward, the PALL and CALM trials will require the use of an anti-CD52 monoclonal antibody in the lymphodepletion regimen.

CAR T cell expansion was detected in blood from day 7 after UCART19 infusion, reaching the peak expansion between day 10 and day 17.

One patient treated in the CALM trial at the second dose level showed the highest peak linked to a long persistence up to 4 months.

The four patients on the FC regimen showed no evidence of CAR T cell expansion.

A similar lack of CAR T cell expansion was seen in two out of 10 patients on the FCA regimen.

The following table illustrates response, duration of remission and re-dosing of UCART19 in the CALM and PALL trial as of the October 2018 data cutoff.

Development Plan

We, in partnership with Servier, plan to continue to advance UCART19 in CALM and PALL in order to determine the recommended Phase 2 dose level and the optimal lymphodepletion regimen, specifically testing the benefits of anti-CD52 monoclonal antibody, alemtuzumab or ALLO-647.

Subject to the continued advancement of the Phase 1 trials, we expect UCART19 to be advanced to potential registrational trials, CALM2 and PALL2, in 2021 .

ALLO-501 and ALLO-501A

ALLO-501 and ALLO-501A are our other allogeneic CAR T cell product candidates targeting CD19.

Anti-CD19 Development Program

CD19 is an antigen expressed on the surface of B cells, including on B cells that are malignant.

B cells are considered non-essential tissue, as they are not required for patient survival.

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, and for children and young adults with ALL that is refractory or has relapsed at least twice.

Our first anti-CD19 product candidate, UCART19, was advanced with our partner, 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.

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

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

Servier sponsored two Phase 1 clinical trials of UCART19 in patients with R/R CD19 positive B-cell ALL, one for adult patients (the CALM trial) and one for pediatric patients (the PALL trial).

The Servier-sponsored trials completed in 2020 and Servier determined that no new patients will be enrolled.

All patients from both studies will continue the long-term follow-up as planned.

We and Servier are reviewing our development strategy for 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 responsible for the manufacture of ALLO-501 and ALLO-501A.

We also lead the clinical development program and are sponsoring the ALPHA trial of ALLO-501 and ALPHA2 trial of ALLO-501A, each for patients with R/R NHL.

ALLO-501 is identical to UCART19 in molecular design, however several modifications have been introduced by us to the manufacturing process for ALLO-501.

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Prior treatment with rituximab is typical for patients with NHL and, depending on the lag time between the rituximab administration and planned ALLO-501 infusion, prior administration of rituximab may interfere with ALLO-501.

As a result, we have removed RQR8 in the next generation of ALLO-501, known as ALLO-501A, as illustrated in the figure below.

As a result, we have removed RQR8 in the next generation of ALLO-501, known as ALLO-501A.

We believe ALLO-501A will have the potential to facilitate treatment of patients who were recently treated with rituximab.

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In this study, we found that ALLO-501 and ALLO-501A exhibited similar characteristics and killing activity.

ALLO-501 and ALLO-501A are jointly developed by us and Servier.

We are the sponsor of the ALLO-501 and ALLO-501A trials and lead the clinical development program.

Target Indication:

Lead Target Indications

Non-Hodgkin Lymphoma (NHL)

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Therefore, there remains a high unmet medical need for newer treatment options, especially for those patients with cancer that is resistant to chemo-immunotherapy.

Acute Lymphoblastic Leukemia (ALL)

ALL is characterized by the proliferation of immature lymphocytes in the bone marrow.

Approximately 5,690 new cases and 1,580 deaths in the United States are estimated in 2021, according to the American Cancer Society.

Approximately 80% of cases of ALL are B-cell ALL.

The risk for developing ALL is highest in children younger than five years of age.

From age five until the mid-20s, the risk declines slowly and begins to steadily rise again after age 50.

Overall, about 40% of all cases of ALL are in adults.

Though most cases occur in children, approximately 80% of deaths from ALL occur in adults.

Over the past four decades pediatric cure rates have reached greater than 80% in developed countries.

This progress can be attributed, in part, to a deeper understanding of the molecular genetics and pathogenesis of the disease, advances in combination chemotherapy, monitoring of minimal residual disease, use of tyrosine kinase inhibitors for Philadelphia chromosome–positive ALL and the success of autologous CAR T cell therapies.

Furthermore, allo-SCT carries a high rate of treatment-related mortality which can occur in approximately 20-30% of patients undergoing allo-SCT.

In patients with R/R ALL after two or more lines of therapy, the median disease-free survival is less than six months.

The five-year overall survival in adults over the age of 60 is approximately 20%, highlighting the high unmet need despite the recent advances in the treatment of ALL.

Initial Phase 1 Results from the ALPHA Trial

In May 2020, in collaboration with Servier, we announced initial results from the ALPHA trial in R/R NHL at the ASCO annual meeting.

The ALPHA trial is a dose-escalation study for ALLO-501 with three separate dose cohorts, from 40 × 10 6 to 360 × 10 6 total cells.

Prior to ALLO-501 treatment, all patients undergo lymphodepletion with a regimen of fludarabine, cyclophosphamide and a low dose or higher dose ALLO-647.

As of the May 11, 2020 data cutoff, 23 patients were enrolled and 22 patients received ALLO-501.

One patient was removed from the study prior to lymphodepletion due to acute renal failure from urinary obstruction.

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

For the efficacy analysis, 19 out of 22 patients reached at least one month assessment as of the May 2020 data cutoff.

Responses were observed across all cell doses and tumor histologies (DLBCL and FL) with an overall response rate (ORR) of 63% and complete response (CR) rate of 37%.

Higher dose ALLO-647 was associated with a higher CR rate of 50%, deeper lymphodepletion and delayed host T cell recovery.

With a median follow-up of 3.8 months, nine of the 12 responding patients (75%) remained in response as of the data cutoff.

Cell Dose and Lympho-depletion regimen

39mg ALLO-647 90mg ALLO-647 All Patients

All 39mg ALLO-647

All 90mg ALLO-647

ORR, n (%) 3 (75%) 3 (75%) 1 (33%) 7 (64%) 4 (67%) 1(50%) 5 (63%) 12/19 (63%)

CR, n (%) 1 (25%) 1 (25%) 1 (33%) 3 (27%) 4 (67%) 0 (0%) 4 (50%) 7/19 (37%)

One of the ongoing responders is a patient with an initial partial response (PR) who progressed by month two.

This patient achieved a CR after re-treatment with the same dose of ALLO-501 and a higher dose (90mg) of ALLO-647.

This patient is reflected as a PR in the table above and not as a CR.

Included in the overall efficacy analysis are three patients who were refractory to prior autologous CAR T therapy (the best response of progressive disease or disease progression within three months).

These patients were also refractory to allogeneic CAR T therapy.

In CAR T naïve patients, the ORR was 75% and the CR rate was 44%.

All Cell Doses + 39mg ALLO-647

120 x 10 6 and 360 x 10 6 CAR + cells +

90mg ALLO-647

All CAR T Naïve Patients

ORR, n (%) 7 (70%) 5 (83%) 12/16 (75%)

CR, n (%) 3 (30%) 4 (67%) 7/16 (44%)

The table below summarizes the adverse events by grade as of the data cutoff.

Grade 1 represents mild toxicity, Grade 2 represents moderate toxicity, Grade 3 represents severe toxicity and Grade 4 represents life threatening toxicity.

Grade 5 toxicity represents toxicity resulting in death.

No dose limiting toxicities, graft-vs-host disease, or Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) was observed.

Adverse Events of Interest Grade 1

N (%) Grade 2

N (%) Grade 3

N (%) Grade 4

N (%) Grade 5

Cytokine Release Syndrome 2 (9%) 4 (18%) 1 (5%) — —

ICANS — — — — —

Graft-versus-Host Disease — — — — —

Infection 5 (23%) 4 (18%) 2 (9%) — —

Infusion Reaction 1 (5%) 9 (41%) 1 (5%) — —

Neutropenia — 1 (5%) 7 (32%) 7 (32%) —

Cytokine release syndrome (CRS) occurred in 32% of the patients, was mainly mild to moderate in severity, manageable with standard recommendations, and all events resolved within a maximum of seven days.

Four patients (18%) experienced serious adverse events (SAEs).

An SAE is defined as any untoward medical occurrence at any dose that (i) results in death;

(ii) is life-threatening (immediate risk of death);

(iii) requires inpatient hospitalization or prolongation of existing hospitalization;

(iv) results in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions);

(v) results in congenital anomaly/birth defect;

or (vi) is considered to be an important medical event.

One patient had Grade 2 pyrexia and Grade 2 cytomegalovirus (CMV) reactivation which resolved in two days and six days, respectively.

One patient had Grade 3 rotavirus infection and Grade 3 hypokalemia which resolved in 15 days and two days, respectively.

One patient had Grade 3 febrile neutropenia and Grade 3 hypotension which each resolved in two days.

One patient had a Grade 3 upper GI hemorrhage which resolved in one day and Grade 3 CMV reactivation which resolved in 25 days.

Adverse events were observed across all dose levels of ALLO-501 and ALLO-647.

SAEs were observed at ALLO-501 cell dose level 40 x 10 6 and 120 x 10 6 and at both dose levels of ALLO-647.

Clinical Development Plan

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

The trial is a dose-escalation study for ALLO-501 with three separate dose cohorts, from 40 × 10 6 to 360 × 10 6 total cells.

Prior to ALLO-501 treatment, all patients undergo lymphodepletion with a regimen of fludarabine, cyclophosphamide and ALLO-647.

We have recently completed enrollment of the three cell dose escalation cohorts, and we are currently exploring the optimal dose and schedule of ALLO-647 in additional cohorts as well as re-dosing of certain patients.

We are exploring the optimal dose and schedule of ALLO-501 and the lymphodepletion regimen in additional cohorts, which includes a cohort of patients receiving a consolidation of ALLO-501 doses.

The consolidation consists of two infusions of 120 million CAR T cells, with a first infusion following the lymphodepletion regimen of fludarabine, cyclophosphamide and ALLO-647 and an initial tumor assessment performed at day 28.

If a patient is in complete response, partial response or stable disease at day 28, a second infusion is given approximately five to six weeks after the first infusion.

Prior to the second cell infusion, a patient will be eligible to receive a modified lymphodepletion consisting only of ALLO-647.

We expect to report updated data from the ALPHA trial in the second quarter of 2021.

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 expect to report initial data from the ALPHA2 trial in the second quarter of 2021.

We plan to initiate an open-label, Phase 1/2, single arm, multicenter clinical trial (the ALPHA2 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-501 will be evaluated as secondary and exploratory objectives, respectively.

In December 2019, the FDA cleared our IND to initiate the ALPHA2 trial and we plan to initiate the trial in the second quarter of 2020, subject to completing the manufacturing of ALLO-501A.

The Phase 1 portion of the ALPHA2 trial is designed to assess the safety and tolerability at increasing dose levels of ALLO-501A, and identify the recommended doses of ALLO-501A and ALLO-647 for use in the Phase 2 portion of the trial.

We also expect certain patients to be eligible for re-treatment.

We expect to dose approximately ten patients in the Phase 1 portion of the trial, subject to the results of the ALPHA trial and ALPHA2 trial including safety data.

Subject to the data as well as follow-up data from ALPHA and ALPHA2 expected in the second half of 2021, we plan to proceed to the Phase 2 portion of the trial in adult patients with R/R large B-cell lymphoma, including DLBCL, or transformed FL by the end of 2021.

All patients treated with ALLO-501 and ALLO-501A will be followed in a long-term follow-up study.

ALLO-715 is an allogeneic CAR T cell product candidate targeting BCMA.

Anti-BCMA Development Program

BCMA is a member of the tumor necrosis factor receptor family and is selectively expressed on immunoglobulin-producing plasma cells, including malignant plasma cells (myeloma cells).

We initiated a Phase 1 clinical trial (the UNIVERSAL trial) of ALLO-715 in adult patients with R/R multiple myeloma in the third quarter of 2019.

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

Two autologous anti-BCMA targeted CAR T therapies have shown promising results in clinical trials and the sponsors have submitted the therapies to the FDA for approval for the treatment of adult patients with multiple myeloma who have received at least three prior therapies.

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.

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.

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

The figure below depicts the construct of ALLO-715.

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.

In addition, emerging clinical data suggest that a gamma secretase inhibitor may increase anti-tumor efficacy of BCMA-targeted autologous CAR T therapy in patients with R/R multiple myeloma.

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.

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

ALLO-605 uses a constitutive cytokine signaling domain and a rituximab-mediated off-switch, as illustrated below.

We expect to submit an IND in the first half of 2021 to initiate a Phase 1 clinical trial of ALLO-605.

Target Indication:

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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.

In the past five years, several new drugs with novel mechanisms (Darzalex, Empliciti, Farydak) have been approved for multiple myeloma, however none of these novel treatments is considered as curative.

More recently, several new drugs with novel mechanisms (Darzalex, Empliciti, Farydak, Xpovio) have been approved for multiple myeloma, however none of these novel treatments is considered as curative.

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 complete response to Darzalex.

Median survival in such patients was just 17.5 months.

Trials of autologous CAR T cell therapies such as bb2121, currently being developed by bluebird bio, Inc.

(bluebird) in partnership with Celgene Corporation, have shown significant promise in multiple myeloma with complete response rates of 31% at doses of 150 × 10 6 to 450 × 10 6 CAR T cells.

Trials of autologous CAR T cell therapies have shown significant promise in multiple myeloma with reported CR rates that are substantially higher.

Initial Phase 1 Results from the UNIVERSAL Trial

In December 2020, we announced initial results from the UNIVERSAL trial in R/R multiple myeloma at the ASH annual meeting.

As of the October 30, 2020 data cutoff, 35 patients were enrolled with 31 patients evaluable for safety and 26 patients evaluable for efficacy.

Patients were refractory to their last line of myeloma therapy, had a median of five prior lines of therapy, and 94% were penta-exposed, which means the patient had previously received at least one CD38 monoclonal antibody, two proteosome inhibitors and two immunomodulatory drugs.

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

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

In the initial dose escalation phase of the UNIVERSAL trial, patients received lymphodepletion followed by ALLO-715 at one of three dose levels (DL1 = 40M cells, DL2 = 160M cells, DL3 = 320M cells) in a 3+3 dose escalation design.

DL4 (480M cells) was added in a subsequent cohort.

Two lymphodepletion regimens were evaluated, with the trial enrollment primarily focused on the FCA lymphodepletion regimen:

F ludarabine 90 mg/m 2 , C yclophosphamide 900 mg/m 2 , and A LLO-647 from 39 to 90mg divided over three days;

C yclophosphamide 900 mg/m 2 and A LLO-647 39mg divided over three days.

Higher CAR T cell doses were associated with an increased response rate and greater cell expansion.

In the DL3 cohort (320M CAR T+ cells), the ORR was 60% with 40% of patients achieving a very good partial response (VGPR) or better (VGPR+).

VGPR+ is defined as a stringent complete response, complete response or VGPR.

Across all cohorts and lymphodepletion regimens, six patients achieved VGPR+, five of whom were in the FCA lymphodepletion regimen.

Minimal residual disease (MRD) assessment was completed in five of the six patients with a VGPR+ response and all achieved an MRD negative status.

MRD negative status occurs when a patient achieves a CR and there is no evidence of tumor cells in the marrow when using sensitive tests such as polymerase chain reaction or flow cytometry.

As of the data cutoff, the overall median follow-up for efficacy was 3.2 months and six out of the nine patients treated with DL3 or DL4 with a response remain in response.

The longest response was ongoing at six months from the DL3 cohort with FCA lymphodepletion.

Cell Dose and LD regimen

ALLO-647 (N=3)

ALLO-647 (N=6)

High ALLO-647 (N=4) ALL

ALLO-647 (N=10)

ALLO-647 (N=3)

— 2 (50%) 3 (50%) 3 (75%) 6 (60%) 1 (33%) — 2 (67%)

— 1 (25%) 3 (50%) 1 (25%) 4 (40%) — — 1 (33%)

*Responses included two subjects with only day 14 assessment and one subject who converted from a confirmed PR to VGPR (pending confirmation).

Of the 31 patients evaluable for safety, there was no graft-vs-host disease or ICANS observed.

Grade 1 and Grade 2 CRS was reported in 14 patients (45%) and was manageable with standard therapies.

Infection events ≥ Grade 3 in the trial was similar to what has been reported in other advanced multiple myeloma studies.

Adverse events ≥ Grade 3 reported as SAEs occurred in 19% of patients.

As previously reported, a single Grade 5 event related to progressive myeloma and conditioning regimen occurred in the CA cohort.

Adverse Events of Interest Grade 1

N (%) Grade 2

N (%) Grade 3

N (%) Grade 4

N (%) Grade 5

N (%) All Grades N (%)

Cytokine Release Syndrome 5 (16%) 9 (29%) — — — 14 (45%)

ICANS — — — — — —

Graft-versus-Host Disease — — — — — —

Infection 2 (7%) 6 (19%) 4 (13%) — 1 (3%) 13 (42%)

Infusion Reaction to ALLO-647

4 (13%) 3 (10%) — — — 7 (23%)

Clinical Development Plan

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

The trial is a dose-escalation study for ALLO-715 with three initial planned dose cohorts, from 40 × 10 6 to 320 × 10 6 total cells.

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

Up to 24 patients are expected to be enrolled in the dose finding stage of the trial.

We also expect to explore different lymphodepletion regimens where the chemotherapy components, specifically fludarabine and cyclophosphamide, will be stepwise removed, and we will also explore the optimal dosing and schedule of ALLO-647.

Additional patients may also be enrolled for further dose expansion.

We expect to report initial data from the trial in the fourth quarter of 2020.

In addition, in January 2020, we entered into a clinical trial collaboration agreement with SpringWorks to evaluate ALLO-715 in combination with SpringWorks’ investigational gamma secretase inhibitor (GSI), nirogacestat, in patients with R/R multiple myeloma.

We plan to initiate this combination trial in the second half of 2020, subject to regulatory clearance.

Future Opportunities

Moving forward, we plan to utilize our allogeneic platform to pursue additional targets of interest.

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 CD70 for the treatment of hematologic malignancies and renal cell carcinoma (ALLO-316), FLT3 for the treatment of AML (ALLO-819), and DLL3 for the treatment of small cell lung cancer (SCLC).

• Renal Cell Carcinoma and ALLO-316.

Analysis using proteomic and immunohistochemistry techniques have demonstrated a high level of CD70 expression in clear cell renal cell carcinoma (ccRCC) cell lines and in more than 80% of human ccRCC tumor samples.

We are exploring the optimal dose and schedule of

ALLO-715 and the lymphodepletion regimen.

We expect to report updated data from the UNIVERSAL trial in the fourth quarter of 2021.

The UNIVERSAL trial recently initiated the evaluation of ALLO-715 in combination with nirogacestat.

Prior to ALLO-715 and nirogacestat treatment, all patients will 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 expect to submit an IND in the first half of 2021 to initiate a Phase 1 clinical trial of our first TurboCAR candidate, ALLO-605, in adult patients with R/R multiple myeloma.

The ALLO-605 trial will assess the safety and tolerability of increasing doses of ALLO-605 along with its clinical efficacy.

The preliminary anti-tumor activity, cell kinetics, safety and tolerability of ALLO-647 in combination with fludarabine and cyclophosphamide, and patient reported outcomes will be evaluated as secondary objectives.

Anti-CD70 Development Program

CD70 is an antigen selectively expressed on several types of cancer cells, including on approximately 80-100% of ccRCC cells and 95% of AML cells, with limited off-tumor expression.

CD70 is also expressed on a portion of DLBCL, multiple myeloma, chronic lymphocytic leukemia and glioblastoma cells as well as on activated T cells.

Accordingly, we believe progressing allogeneic CAR T cell therapies directed against CD70 could be promising in solid tumor indications as well as hematological malignancies.

In December 2020, the FDA cleared an IND to initiate a Phase 1 clinical trial (the TRAVERSE trial) of ALLO-316 in adult patients with advanced or metastatic ccRCC.

We plan to initiate the TRAVERSE trial in the first quarter of 2021.

We also plan to investigate the use of ALLO-316 for a second indication in R/R AML.

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.

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.

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.

Lead Target Indications:

Clear Cell Renal Cell Carcinoma

ccRCC is the most common subtype of renal cancer.

Approximately 76,080 new cases of renal cell carcinoma are estimated to be diagnosed in the United States and 13,780 deaths are estimated in 2021, according to the American Cancer Society.

While the median survival for patients with stage IV disease was a little over one year when cytokines were the predominant systemic therapies, analyses from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) based upon more than 2,200 patients treated with targeted therapies report a median survival of 28 months in patients who were eligible for clinical trials.

Another contemporary trial using targeted therapy reported a median survival of 28 to 29 months in patients treated with sunitinib or pazopanib, mirroring the IMDC results.

We have selected an anti-CD70 CAR T candidate, ALLO-316, and are progressing IND-enabling studies, with the goal of submitting an IND by year-end 2020.

• Acute Myeloid Leukemia and ALLO-316 and ALLO-819 .

AML is a high unmet medical need with few treatment options.

It is a cancer of bone marrow stem cells and is the most common type of leukemia in adults.

The American Cancer Society estimates 19,940 new diagnoses and 11,180 deaths in the United States in 2020.

The five-year survival rate for patients with early-stage disease is greater than 90% compared with less than 15% for those with advanced kidney cancer.

Systemic therapy (including immunotherapy and molecularly targeted agents), surgery, and radiation therapy all may have a role in the treatment paradigm depending on the extent of disease, sites of involvement, and patient-specific factors.

While vascular endothelial growth factor (VEGF)-directed therapies (e.g.

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%.

Patients who progress on immune checkpoint-based combination therapies can be treated with cabozantinib, pazopanip, temsirolimus or high dose IL-2.

There remains a need for novel, mechanistically distinct therapies.

Acute Myeloid Leukemia

AML is a cancer of bone marrow stem cells and is the most common type of acute leukemia in adults.

The American Cancer Society estimated 19,940 new diagnoses and 11,180 deaths in the United States in 2020.

Although advances in supportive care and prognostic risk stratification have optimized established therapies, overall long-term survival remains poor and AML is a high unmet medical need.

Patients have a poor prognosis despite improvements in chemotherapy regimens and supportive care.

CD70 is expressed on AML bulk cells and leukemic stem cells and we expect our planned clinical trial of ALLO-316 to allow for the treatment of patients with AML.

In addition, FLT3 is a receptor tyrosine kinase that is overactive in AML blasts.

AML is a biologically and clinically heterogenous disease.

The identification of recurrent genetic mutations, such as FLT3-ITD, NMP1 and CEBPA, has helped refine individual prognosis and guide management.

Despite advances in supportive care, the backbone of therapy remains a combination of cytarabine- and anthracycline-based regimens with allogeneic stem cell transplantation for the medically-fit patients.

Twenty to 30 percent of young adult patients and 50 percent of older adults with newly diagnosed AML will fail to attain a CR with intensive induction chemotherapy due to drug resistance or death.

In addition, a percentage of patients who initially attain a CR will relapse.

Relapse after conventional chemotherapy remains a major problem in patients with myeloid malignancies such as AML, and the major cause of death after diagnosis of AML is from relapsed disease.

The development of new treatments, in concert with improved genetic profiling and risk stratification, are greatly needed in the goal to achieve incremental gains in remission and survival.

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 four separate dose cohorts, from 40 × 10 6 to 480 × 10 6 total cells.

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

We expect to initiate the TRAVERSE trial in the first quarter of 2021.

Future Opportunities

Moving forward, we plan to utilize our allogeneic platform to pursue additional targets of interest.

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 (SCLC).

• Acute Myeloid Leukemia and FLT3 .

FLT3 is a receptor tyrosine kinase that is overactive in AML blasts.

We have conducted in vitro and in vivo studies of our anti-FLT3 CAR T candidate, ALLO-819, that show anti-tumor activity against blasts present in bone marrow from AML patients and in mice.

We are currently advancing an IND-enabling data set for ALLO-819.

We are currently testing increasing activity of our clinical candidate with the addition of a TurboCAR cytokine signaling domain ahead of finalizing an IND-enabling data set.

• Small Cell Lung Cancer and DLL3 .

DLL3 is a target which is being pursued for SCLC using ADCs, bi-specifics and autologous CAR T therapies.

DLL3 is a target which is being pursued for SCLC using antibody drug conjugates, bi-specifics and autologous CAR T therapies.

According to the American Cancer Society, approximately 235,760 new cases of lung cancer are expected to be diagnosed in the United States in 2021 and SCLC comprises approximately 10-15% of all lung cancers.

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We believe an allogeneic anti-DLL3 CAR T cell product candidate could be used alone or in combination with PD-1/PD-L1 therapy.

We are currently testing and refining constructs for an anti-DLL3 CAR T candidate, and following completion we plan to progress to IND-enabling studies.

We also plan to enhance our platform using next-generation technologies such as TurboCARs, switch technologies, including small-molecule induced off-switch, site-specific integration and multi-specific CARs.

• TurboCARs and ALLO-605 .

Mimicking cytokine activation signaling within a CAR T cell could enhance the proliferative potential, migratory behavior, and killing activity of cells.

We are currently testing and refining constructs for an anti-DLL3 CAR T candidate and investigating the use of TurboCARs and next generation TurboCARs designed to overcome negative effects of the tumor microenvironment.

Following completion of these studies, we plan to progress to IND-enabling studies.

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.

• TurboCARs .

Mimicking cytokine signaling within a CAR T cell could enhance the proliferative potential, migratory behavior, activation status and killing activity of cells.

Such modulation may enhance the anti-tumor activity and durability of CAR T cells without affecting non-engineered immune cells.

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

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

We are progressing our first TurboCAR, ALLO-605, which targets BCMA and uses a constitutive cytokine signaling domain and a rituximab-mediated off-switch, with the goal of submitting an IND in 2021.

We are progressing our first TurboCAR, ALLO-605, which targets BCMA and uses a constitutive cytokine signaling domain and a rituximab-mediated off-switch.

We plan to submit an IND to initiate a Phase 1 clinical trial of ALLO-605 in the first half of 2021.

• Renewable Cell Source.

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We commenced the research collaboration with Notch in late 2019.

We commenced the research collaboration with Notch in 2019.

• Site-Specific Integration .

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This may be accomplished by including two antigen binding domains with different specificity in a single polypeptide encoding the CAR or in two separate polypeptides each encoding a CAR with different antigen specificity.

• Increasing tumor specificity of targets:

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.

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.

Our Manufacturing Strategy

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

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.

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

Servier is responsible for UCART19 manufacturing and is working with a CMO in Europe to provide clinical supply for the CALM and PALL clinical trials.

ALLO-501 is identical in molecular design to UCART19, but is produced using a modified manufacturing process, optimized by us.

ALLO-501, ALLO-501A and ALLO-715 are manufactured in the United States by a CMO, and we will manage all other aspects of the supply, including planning, CMO oversight, disposition and distribution logistics.

The CMO that is manufacturing the clinical supply of ALLO-501, ALLO-501A and ALLO-715 is subject to cGMP requirements, using qualified equipment and materials.

Our cell-based product candidates are currently manufactured in the United States by a CMO, and we manage all other aspects of the supply, including planning, CMO oversight, disposition and distribution logistics.

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.

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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 plan to phase the build-out of the facility, and expect to complete the build-out of the majority of the facility in the second half of 2020 and initiate cGMP manufacturing operations in 2021.

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 expect to initiate cGMP manufacturing operations in 2021.

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.

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.

We believe the use of contract manufacturing and testing for our first clinical product candidates has allowed us to rapidly prepare for clinical trials in accordance with our development plans.

We expect third-party manufacturers will be capable of providing and processing sufficient quantities of our product candidates to meet anticipated clinical trial demands.

We also utilize a CMO in the United States for the manufacture and supply of ALLO-647.

We plan to create a robust supply chain with redundant sources of supply comprised of both internal and external infrastructure.

Strategic Agreements

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), and the Notch Collaboration Agreement

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

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

Intellectual Property

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

We have exclusive worldwide rights to these patents for certain antigen targets, including BCMA, and have U.S.

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

rights to these patents for CD19.

We also have rights to a Cellectis U.S.

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

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

Our patent portfolio includes protection for our lead product candidates, UCART19, ALLO-501, ALLO-501A and ALLO-715, as well as our other research-stage candidates.

With respect to UCART19, 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 UCART19, ALLO-501 and ALLO-501A.

Our patent portfolio includes protection for our lead product candidates, ALLO-501, ALLO-501A and ALLO-715, as well as our other 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-715, we have an exclusive license from Pfizer to patent rights covering ALLO-715 in the United States and in foreign jurisdictions.

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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.

Novartis and Kite were the first to achieve FDA approval for autologous T cell therapies.

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

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

We also anticipate competition from other cell-based and immune-based therapies in development.

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

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 obtained FDA approval to commercialize Yescarta, the first CAR T cell product candidate for the treatment of adult patients with R/R large B-cell lymphoma.

Due to the promising therapeutic effect of T cell therapies in clinical trials, we anticipate increasing competition from existing and new companies developing these therapies, as well as in the development of allogeneic T cell therapies.

Potential cell therapy competitors include, but are not limited to:

• Allogeneic T cell therapy competition :

Atara Biotherapeutics, Inc., Celyad S.A., CRISPR Therapeutics AG, Editas Medicine, Inc., Fate Therapeutics Inc., Gilead Sciences, Inc.

(acquired Kite), Intellia Therapeutics, Inc., Poseida Therapeutics, Inc., and Precision Biosciences, Inc.

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

A supplemental BLA for Yescarta for R/R FL and R/R marginal zone lymphoma was submitted in September 2020.

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

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.

BMS and bluebird bio, Inc.

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

In addition, Johnson & Johnson and partner Legend Bio have initiated a rolling BLA submission for an anti-BCMA autologous T cell therapy, ciltacabtagene autoleucel, for the same indication.

Autologous T cell therapies are being developed by a number of additional companies, including but not limited to Adaptimmune Therapeutics PLC, ArsenalBio, Autolus Therapeutics plc, Gilead Sciences, Inc., Gracell Biotechnologies Inc., Iovance Biotherapeutics, Inc., Mustang Bio, Inc., Novartis International AG, Pact Pharma, Inc., TCR² Therapeutics Inc., Tmunity Therapeutics, Inc., and Unum 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 Atara Biotherapeutics, Inc., Caribou Biosciences, Inc., Celyad S.A., CRISPR Therapeutics AG, Editas Medicine, Inc., Gilead Sciences, Inc., Intellia Therapeutics, Inc., Poseida Therapeutics, Inc., Precision Biosciences, Inc., Sana Biotechnology, Inc., and Tessa Therapeutics Ltd.

Additionally, Cellectis has several fully-owned allogeneic CAR programs that could compete with programs that fall outside our agreement with Cellectis.

• Autologous T cell therapy competition :

Adaptimmune Therapeutics PLC, Autolus Therapeutics plc, bluebird bio, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Johnson & Johnson, Iovance Biotherapeutics, Inc., Mustang Bio, Inc., Novartis International AG, TCR² Therapeutics Inc., Tmunity Therapeutics, Inc., and Unum Therapeutics Inc.

There are also cell therapies under development that are based upon cell types other than the common type of T cells used by us and known as alpha/beta T cells.

These include product candidates derived from natural killer cells, natural killer T cells, and gamma/delta T cells.

Companies developing such therapies include Fortress Biotech, Inc., Gamida Cell Ltd., GammaDelta Therapeutics Limited, Fate Therapeutics, Inc., In8bio, Inc., Kuur Therapeutics Inc., Lyell Immunopharma, Inc., Nkarta, Inc., Artiva Biotherapeutics, Inc.

and Takeda Pharmaceutical Company Limited.

Competition may also arise from non-cell based immune oncology platforms.

For instance, we may experience competition from companies, such as Amgen Inc., Bristol-Myers Squibb Company, F.

Hoffmann-La Roche AG, Genmab A/S, GlaxoSmithKline plc, MacroGenics, Inc., Merus N.V., Regeneron Pharmaceuticals, Inc., and Xencor Inc., that are pursuing bispecific antibodies, which 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.

Additionally, companies, such as Amgen Inc., Daiichi Sankyo Company, Limited, GlaxoSmithKline plc, ImmunoGen, Inc., Immunomedics, Inc., and Seattle Genetics, Inc., are pursuing antibody drug conjugates, which utilize the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells.

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

Hoffmann-La Roche AG, Genmab A/S, GlaxoSmithKline plc, Harpoon Therapeutics, Inc., MacroGenics, Inc., Merus N.V., 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.

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., are pursuing antibody drug conjugates, which utilize the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells.

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

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

Post-Approval Requirements

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The FDA also may require post-marketing testing, known as Phase 4 testing, and surveillance to monitor the effects of an approved product.

Discovery of previously unknown problems with a product or the failure to comply with applicable FDA requirements can have negative consequences, including adverse publicity, judicial or administrative enforcement, warning letters from the FDA, mandated corrective advertising or communications with doctors, and civil or criminal penalties, among others.

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

management measures.

warning letters from the FDA, mandated corrective advertising or communications with doctors, and civil or criminal penalties, among others.

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

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Our practices may not in all cases meet all of the criteria for protection under a statutory exception or regulatory safe harbor.

Additionally, the intent standard under the federal Anti-Kickback Statute was amended by the Patient Protection and Affordable Care Act of 2010, as amended by the Health Care and Education Reconciliation Act of 2010, collectively, the Affordable Care Act, to a stricter standard such that a person or entity no longer needs to have actual knowledge of the federal

Anti-Kickback Statute or specific intent to violate it in order to have committed a violation.

Rather, if “one purpose” of the remuneration is to induce referrals, the federal Anti-Kickback Statute is violated.

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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, as defined by such law, 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.

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) 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.

Beginning in 2022, applicable manufacturers also will be required to report such information regarding its payments and other transfers of value to physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified registered nurse anesthetists and certified nurse midwives during the previous year.

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.

Some states also impose requirements on manufacturers and distributors to establish the pedigree of product in the chain of distribution, including some states that require manufacturers and others to adopt new technology capable of tracking and tracing product as it moves through the distribution chain.

tracing product as it moves through the distribution chain.

Several states have enacted legislation requiring pharmaceutical and biotechnology companies to establish marketing compliance programs, file periodic reports with the state, make periodic public disclosures on sales, marketing, pricing, clinical trials and other activities, and/or register their sales representatives, as well as to prohibit pharmacies and other healthcare entities from providing certain physician prescribing data to pharmaceutical and biotechnology companies for use in sales and marketing, and to prohibit certain other sales and marketing practices.

All of our activities are potentially subject to federal and state consumer protection and unfair competition laws.

If our operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that apply to us, we may be subject to penalties, including without limitation, civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid, refusal to allow us to enter into government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, additional reporting requirements and/or oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

If our operations are found to be in violation of any of the federal and state healthcare laws described above or any other governmental regulations that apply to us, we may be subject to significant penalties, including without limitation, civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government programs, such as Medicare and Medicaid, refusal to allow us to enter into government contracts, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, additional reporting requirements and/or oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

Coverage, Pricing and Reimbursement

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In the United States and some foreign jurisdictions, there have been, and continue to be, several legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay marketing approval of product candidates, restrict or regulate post-approval activities, and affect the ability to profitably sell product candidates for which marketing approval is obtained.

Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access.

Among policy makers and payors in the United States and elsewhere, there is significant

interest in promoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality and/or expanding access.

In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives.

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Among the Affordable Care Act provisions of importance to the pharmaceutical and biotechnology industries, in addition to those otherwise described above, are the following:

• created an annual, nondeductible fee on any entity that manufactures or imports certain specified branded prescription drugs and biologic agents apportioned among these entities according to their market share in some government healthcare programs that began in 2011;

• increased the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program, retroactive to January 1, 2010, to 23.1% and 13% of the average manufacturer price for most branded and generic drugs, respectively, and capped the total rebate amount for innovator drugs at 100% of the Average Manufacturer Price (AMP);

• increased the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13% of the average manufacturer price for most branded and generic drugs, respectively, and capped the total rebate amount for innovator drugs at 100% of the Average Manufacturer Price (AMP);

• created a new Medicare Part D coverage gap discount program, in which manufacturers must now agree to offer 70% point-of-sale discounts, off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;

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• established a Center for Medicare and Medicaid Innovation at CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending.

• created a licensure framework for follow on biologic products.

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

Since January 2017, the current U.S.

President has signed two executive orders and other directives designed to delay, circumvent, or loosen certain requirements mandated by the Affordable Care Act.

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

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

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

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

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”.

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.

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Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the Affordable Care Act are invalid as well.

It is unclear how this decision, future decisions, subsequent appeals, and other efforts to repeal and replace the Affordable Care Act will impact the Affordable Care Act.

Supreme Court is currently reviewing this case, but it is unknown when a decision will be reached.

Although the U.S.

Supreme Court has yet to rule on the constitutionality of the Affordable Care Act, on January 28, 2021, President Biden issued an executive order to initiate a special enrollment period from February 15, 2021 through May 15, 2021 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 the Supreme Court ruling, other such litigation, and the healthcare reform measures of the Biden administration will impact the Affordable Care Act.

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

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

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

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

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

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 2030 unless additional Congressional action is taken.

However, COVID-19 relief support legislation suspended the 2% Medicare sequester from May 1, 2020 through March 31, 2021.

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

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

At the federal level, the U.S.

President’s administration’s budget proposal for fiscal year 2020 contains further drug price control measures that could be enacted during the budget process or in other future legislation, including, for example, measures to permit Medicare Part D plans to negotiate the price of certain drugs under Medicare Part B, to allow some states to negotiate drug prices under Medicaid, and to eliminate cost sharing for generic drugs for low-income patients.

Additionally, the U.S.

President’s administration released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products paid by consumers.

HHS has solicited feedback on some of these measures and has implemented others under its existing authority.

For example, in May 2019, CMS issued a final rule to allow Medicare Advantage plans the option to use step therapy for Part B drugs beginning January 1, 2020.

This final rule codified CMS’s policy change that was effective January 1, 2019.

While some of these and other measures may require additional authorization to become effective, Congress and the U.S.

President’s administration have each indicated that it will continue to seek new legislative and/or administrative measures to control drug costs.

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, effective November 30, 2020, implementing a portion of the importation executive order providing guidance 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 March 22, 2021.

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, effective January 1, 2021.

On December 28, 2020, the United States District Court in Northern California issued a nationwide preliminary injunction against implementation of the interim final rule.

However, it is unclear whether the Biden administration will work to reverse these measures or pursue similar policy initiatives.

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

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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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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.

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.

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The CCPA requires covered companies to provide new disclosures to California consumers, provides such consumers new ways to opt-out of certain sales of personal information, and allows for a new cause of action for data breaches.

As our business progresses, the CCPA may 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.

As of February 24, 2020, we had 206 total employees and 205 full-time employees.

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

Human Capital

As of February 1, 2021, we had 265 total employees, of which 264 are full-time.

Of our full-time employees, 69 hold Ph.D.

degrees, and 195 are engaged in research, development and technical operations.

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

Substantially all 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.

We consider our relationship with our employees to be good.

We believe that our employee morale is healthy and consider our relationship with our employees to be good.

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

(1) our “One Allogene” culture, (2) diversity, equity 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.

One Allogene Culture

We have recently advanced an expression of our culture under the framework of “One Allogene”:

We only succeed as a team.

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

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

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

We aim for excellence and give it our all.

We pursue scientific innovation with a focus on quality and integrity in everything we do to forever change how cancer is treated.

We take ownership and get things done.

We are leaders who embrace urgency, initiative and follow through, with the humility to know each one of us is vital to making AlloCAR T therapy a reality.

We are good to one another.

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

We are creating a scientific revolution.

We are One Allogene

These core elements of our culture are meant to define how and why we do business.

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

Diversity, Equity and Inclusion

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

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

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

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

As of February 1, 2021, our employees were self-reportedly 49% women.

Of our Director-level and above employees, 42% were self-reportedly women.

In addition, as of February 1, 2021, 66% of all employees were self-reportedly ethnic or racial minorities in the U.S., with 52% Asian, 3% Black or African American, 5% Hispanic or Latino and 5% 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 30% Asian, 1% Black or African American, 1% Hispanic or Latino and 6% 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.

We have and will continue to conduct unconscious bias training and provide guidance with respect to best practices with a focus on DEI for interviewers.

Our recruiters and hiring managers are also encouraged to consider candidates from underrepresented groups and to have diverse interview panels.

In addition, we have an Employee Referral Bonus Program that rewards employees for referring candidates from underrepresented groups that are ultimately hired.

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

We are also progressing the ongoing development of an inclusive work environment that encourages:

• Respectful communication and cooperation between all employees.

• Valuing and soliciting input, feedback and opinions from relevant staff.

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

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

To champion our efforts in this area, we established a governance structure and formed a DEI Committee as well as an associated DEI Advisory Board, each of which is comprised of employees of various levels, departments and backgrounds.

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.

We believe in equal pay for equal work.

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

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

internal equity;

job location;

relevant experience;

and individual, department and company performance.

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

In 2020, we conducted a pay equity analysis which we believe demonstrated that our compensation practices and structure are equitable.

If we identify employees with unjustified pay gaps, we review and take appropriate action to ensure fidelity between our stated philosophy and actions.

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

Recruitment, Development and Retention

Successful execution of our strategy is dependent on attracting, developing and retaining our employees.

We believe our leadership in the field of allogeneic cell therapy and our culture have allowed us to recruit a talented workforce.

we recruited over 90 new employees.

Our average time to hire was less than three months and a significant majority of candidates accepted our offers.

We believe our total compensation package also helps recruit and retain our employees.

We strive to provide pay, benefits, and services that are competitive to market and create incentives to attract and retain employees.

Our compensation package includes market-competitive pay, broad-based stock grants, health care and 401(k) plan benefits, paid time off and family leave, among others.

We also provide annual incentive bonus opportunities that are tied to both company performance as well as individual performance to foster a pay-for-performance culture.

Developing our employees is important, and we focus on providing training opportunities and promotional opportunities.

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

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

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

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

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

We believe Allogene is an attractive workplace and our voluntary attrition rate for 2020 was less than 10%.

However, we are in a highly competitive field and geographic region for life science talent and historically have faced proportionally higher attrition among our research, development and technical operations teams than our general and administrative teams.

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, social distancing and temperature check requirements.

We continue to provide updates regarding COVID-19 and communicate with our employees on a frequent basis.

For employees working remotely, we have provided collaboration tools and resources, including loaning certain office equipment and providing trainings to help leaders effectively lead and manage remote teams.

In addition, we enhanced and promoted programs to support our culture initiatives and employees’ wellbeing.

For instance, we have implemented Human Resources-led virtual check-ins with our employees (both new hires and tenured employees), conducted surveys regarding culture and COVID-19 related initiatives, and also encouraged skip-level meetings in addition to emphasizing the importance of managers having regular 1:1 meetings with their team members.

We also instituted biweekly virtual town-halls led by our Chief Executive Officer to provide all employees updates relating to our business and the opportunity to anonymously ask questions of our leadership team.

In addition, we provided emergency pay to any employees unable to work due to the pandemic impact and implemented virtual fitness and meditation classes.

We plan to stay engaged with our employees and work to continuously improve to strengthen Allogene’s culture and commitment to patients and stockholders.

Corporate Information

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Our corporate website address is www.allogene.com.

We make available, free of charge on our website our annual report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, and any amendments to those reports, as soon as reasonably practicable after filing such reports with the Securities and Exchange Commission.

Alternatively, you may access these reports at the SEC’s website at www.sec.gov.

Information contained on or accessible through our website is not a part of this report, and the inclusion of our website address in this report is an inactive textual reference only.

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