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Item 1. Business

2022-02-23 compared with 2021-02-25 · 299 added, 336 removed, 761 unchanged (45% of the section changed)

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

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

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

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The entire manufacturing process is dependent on the viability of each patient’s T cells and takes approximately two to four weeks.

As seen in the registrational trials for Kymriah and Yescarta, 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.

Obtaining a manufacturing slot, collecting patient cells, and scheduling can extend the time to treatment by additional weeks.

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

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

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

We have multiple clinical trials ongoing and have a deep pipeline to further the research and development of allogeneic CAR T cell product candidates in both hematological malignancies and solid tumors.

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

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

Our allogeneic T cell development strategy has four key pillars:

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We use Cellectis, S.A.

(Cellectis), TALEN gene-editing technology with the goal of limiting the risk of GvHD by engineering T cells to lack functional T cell receptors (TCRs) that are no longer capable of recognizing a patient’s normal tissue as foreign.

(Cellectis), TALEN gene-editing technology to limit the risk of GvHD by engineering T cells to lack functional T cell receptors (TCRs) that are no longer capable of recognizing a patient’s normal tissue as foreign.

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

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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 current good manufacturing practices (cGMP) manufacturing at our facility in 2021.

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

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

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

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

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Our lead product candidates include:

We are sponsoring a Phase 1 clinical trial (the ALPHA trial) of ALLO-501 in patients with the most common R/R non-Hodgkin lymphoma (NHL) subtypes.

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

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

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

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.

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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.

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

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

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

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 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.

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

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

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

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).

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

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

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

ALLO-605 is our first product candidate to incorporate our TurboCAR technology.

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

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

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

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

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

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

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

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

Our History and Team

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

In particular, Dr.

Belldegrun’s experience in T cell therapy dates back to his time at the National Cancer Institute as a research fellow in surgical oncology and immunotherapy with Steven Rosenberg, M.D., Ph.D, a recognized pioneer in immuno-oncology.

Our President and Chief Executive Officer, Dr.

Chang, served as Executive Vice President of Kite and held senior leadership roles at Amgen, Inc.

Moreover, both Dr.

In particular, both Dr.

Belldegrun and Dr.

Chang led the development and approval of Yescarta at Kite.

Additionally, our Chief Technical Officer, Alison Moore, Ph.D., was previously Senior Vice President, Process Development at Amgen, where she led the development, deployment and oversight of manufacturing for approximately 80 multi-modality assets.

Moore has over 25 years of experience in biotechnology, including in the immuno-oncology space leading process development of Amgen’s comprehensive bi-specific T cell engager production platform.

In September 2019, Rafael Amado, M.D., joined us as our Executive Vice President of Research and Development and Chief Medical Officer.

Amado has more than 15 years of biotechnology and pharmaceutical industry experience leading clinical and research teams, and he most recently served as President, Research and Development, at Adaptimmune Therapeutics plc, a T cell therapy company, from August 2018 to August 2019, and as Chief Medical Officer from March 2015.

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

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

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

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

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

We 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.

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

• Expand our leadership position within hematologic indications .

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.

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 AML.

For example, we believe BCMA is a promising target, as initial results from the UNIVERSAL trial have shown encouraging efficacy and manageable safety.

We also plan to develop additional allogeneic T cell product candidates targeting other antigens found on hematologic malignancies, including ALLO-316 targeting CD70, which may be applicable to multiple hematological malignancies, and ALLO-819 targeting FLT3 for the treatment of AML.

• 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 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.

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

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

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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.

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

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

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

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• 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.

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

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

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.

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

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

When T cells with

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

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

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The process from leukapheresis to delivery to the clinical center takes approximately two to four weeks.

Obtaining a manufacturing slot, collecting patient cells, and scheduling can extend the time to treatment by additional weeks.

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

• Lengthy Vein-to-Vein Time .

Due to the individualized manufacturing process, patients must wait approximately two to four weeks to be treated with their engineered cells.

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

• Lengthy Delivery Time .

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

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.

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

• Variable Potency .

In many cases, patients have T cells that have been damaged or weakened due to prior chemotherapy or hematopoietic stem-cell transplant.

In some cases, patients may have T cells that have been damaged or weakened due to prior chemotherapy or hematopoietic stem-cell transplant.

Compromised T cells may not proliferate well during manufacturing or may produce cells with insufficient potency that cannot be used for patient treatment, resulting in manufacturing failures, or that can show poor expansion and activity in patients.

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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.

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

The figure below illustrates how we utilize Cellectis’s TALEN and electroporation technology to inactivate the genes coding for TCRα and CD52 in our allogeneic T cells for UCART19.

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To selectively deplete a patient’s immune cells while sparing the therapeutic allogeneic T cells, we use TALEN gene editing to inactivate the CD52 gene in allogeneic T cells, thus protecting allogeneic T cells from the anti-CD52 antibody mediated depletion.

By administering anti-CD52 antibody prior to infusing our product candidates, we believe we can 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 expand and actively target and destroy cancer cells.

As illustrated below, by administering anti-CD52 antibody prior to infusing our product candidates, we believe we can 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 expand and actively target and destroy cancer cells.

We also believe our approach is unique and differentiated.

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

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

The allogeneic cells then undergo a

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

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

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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.

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

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

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

manufacturing process and had no clinical significance.

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

The abnormality occurred in the patient after the cell product was administered and involved regions of the T cell receptor and immunoglobulin genes known to undergo rearrangement as part of the T cell or B cell maturation process.

The FDA found that we satisfactorily addressed all clinical hold issues and removed the hold in January 2022.

We have resumed our studies as discussed in further detail below.

Anti-CD19 Development Program

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

Multiple autologous anti-CD19 targeted CAR T therapies have shown promising results and have been approved by the FDA as therapies for adults with R/R large B-cell lymphoma, adults with R/R mantle cell lymphoma, and for children and young adults with ALL that is refractory or has relapsed at least twice.

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

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

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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.

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

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

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

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

ALLO-501A has been manufactured from several donors under non-cGMP conditions and has been compared to the current version of ALLO-501 in vitro.

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

Lead Target Indications

Lead Target Indication:

Non-Hodgkin Lymphoma (NHL)

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

Despite recent therapeutic advances, more than 50% of patients with aggressive B-cell NHL are incurable using existing approved therapies.

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

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

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

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

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

7%, partial response:

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

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.

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.

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

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

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

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

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

Data Cutoff October 18, 2021

Enrolled 50 29

Evaluable for Safety 49* 28**

Evaluable for Efficacy 40 #

% Initiated Treatment 98% 97%

Median Days Enrollment to Treatment Initiation 5 2

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

** One patient developed COVID-19 before treatment

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

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

two treated patients yet to reach tumor assessment at data cutoff

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

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

The trials explored two consolidation cohorts.

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

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

Response Rates Across the ALPHA and ALPHA2 Trials

ALPHA ALLO-501 Response Rates

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

Single dose (N=18) Consolidation

(N=26) Single dose

(N=11) Consolidation

(N=3) All LBCL

(N=14) All Patients

Overall Response Rate (ORR), n (%) 14 (78%) 7 (88%) 21 (81%) 7 (64%) 2 (67%) 9 (64%) 30 (75%)

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

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

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

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

ALPHA2 ALLO-501A Response Rates

(N=6) Consolidation 1

(N=9) Consolidation 2

(N=10) All Patients

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

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

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

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

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

Combined ALPHA + ALPHA2 Consolidation Response Rates

Consolidation 1 Consolidation 2 All Patients

N = 16 N = 14 N = 30

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

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

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 — — — — —

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

Safety Across the ALPHA and ALPHA2 Trials

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

ALPHA ALLO-501 Safety

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

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

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

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

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

GvHD 0 0 0 0 0 0 0 0 0 0

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

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

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

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.

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

*Infusion-related reactions (IRR).

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

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

ALPHA2 ALLO-501A Safety

(N=1) DL2 120M

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

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

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

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

CRS 100% 0 17% 0 0 0 10% 0 11% 0

Neurotoxicity 100% 0 33% 0 9% 0 20% 0 21% 0

GvHD 0 0 0 0 0 0 0 0 0 0

Infection 100% 0 83% 17% 27% 0 10% 10% 36% 7%

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

Serious AE 0 100% 18% 30% 39%

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

There were no treatment-emergent deaths in the trial.

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

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

Clinical Development Plan

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

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

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.

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

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

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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.

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.

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

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

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

Anti-BCMA Development Program

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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.

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

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

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

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.

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

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

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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.

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

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.

We initiated the Phase 1 clinical trial (the IGNITE trial) of ALLO-605 in mid-2021.

Target Indication:

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Median survival in such patients was just 17.5 months.

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

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.

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

Results from the Phase 1 ALLO-715 UNIVERSAL Trial

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

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

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

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

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

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.

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

fludarabine, Cy and ALLO-647 or CA:

Cy and ALLO-647 only).

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

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

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

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

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

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

(N=11) Mid ALLO-647

(N=10) High ALLO-647

(N=3) ALL ALLO-647

ORR, n (%) 7 (64%) 8 (80%) 2 (67%) 17 (71%)

VGPR+ Rate, n (%) 5 (46%) 5 (50%) 1 (33%) 11 (46%)

CR/sCR Rate, n (%) 3 (27%) 3 (30%) 0 6 (25%)

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

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

The longest ongoing response after cell infusion was 12 months.

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

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

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

Grade 3+ neutropenia occurred in 70% of patients.

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

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

Adverse Events of Interest Grade 1

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N (%) Grade 5

N (%) All Grades N (%)

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

ICANS — — — — — —

Graft-versus-Host Disease — — — — — —

N (%) All Grades

CRS 13 (30%) 10 (23%) 1 (2%) 0 0 24 (56%)

Neurotoxicity 4 (9%) 2 (5%) 0 0 0 6 (14%)

GvHD 0 0 0 0 0 0

Infection 3 (7%) 10 (23%) 7 (16%) 0 3 (7%) 23 (54%)

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

4 (13%) 3 (10%) — — — 7 (23%)

Clinical Development Plan

The UNIVERSAL trial is an open-label, Phase 1, single arm, multicenter clinical trial evaluating the safety and tolerability of ALLO-715 in adult patients with R/R multiple myeloma.

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

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

We are exploring the optimal dose and schedule of

ALLO-715 and 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.

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

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

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

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

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

We 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.

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

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

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.

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

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

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.

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

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

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

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

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:

In the first half of 2021, we initiated a Phase 1 clinical trial (the TRAVERSE trial) of ALLO-316 in adult patients with advanced or metastatic ccRCC.

Lead Target Indication:

Clear Cell Renal Cell Carcinoma

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Approximately 79,000 new cases of renal cell carcinoma are estimated to be diagnosed in the United States and 13,920 deaths are estimated in 2022, according to the American Cancer Society.

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.

The five-year survival rate for patients with advanced kidney cancer is less than 15%.

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.

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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.

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.

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

Clinical Development Plan

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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.

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

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

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

Future Opportunities

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

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

SCLC is responsive to chemotherapy, but recurrence arises rapidly, with less than 7% of patients surviving over five years.

SCLC has shown to be responsive to immunotherapy with approximately one-third of patients responding to PD-1/PD-L1 therapy and achieving a median overall survival of approximately thirteen months for patients who received PD-L1 and platinum-based chemotherapy.

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 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.

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.

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 .

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

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

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

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

• Renewable Cell Source.

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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.

We commenced the research collaboration with Notch in 2019.

• Site-Specific Integration .

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Such site-specific integration may allow the CAR or other transgenes to be introduced into T cells in a more homogeneous manner, allowing a more uniform and controlled expression of the proteins, with the goal of generating CAR T cell products that behave in a more consistent and predictable manner.

It may also allow longer sequences of DNA to be inserted into the T cell, allowing for the expression of genes that would not otherwise be feasible with viral based gene insertion.

• Multi-specific CARs.

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

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

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

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

We also utilize

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

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

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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.

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

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

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

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

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

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

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

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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, ALLO-501, ALLO-501A and ALLO-715, as well as our other research-stage candidates.

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

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

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

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

These rights include composition of matter protection for ALLO-715 and methods of making and using ALLO-715.

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

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

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

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

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(4) manufacturing processes, preconditioning methods, and dosing regimens;

and (5) reducing GvHD, and methods for genetically engineering immune cells suitable for allogeneic use.

and (5) immune evasion and other gene and cell engineering technology.

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

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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.

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).

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

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

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

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

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

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

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

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

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.

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

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

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

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

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

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

This includes 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.

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

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

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

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.

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

Companies developing such therapies include Adicet Bio, Inc., Artiva Biotherapeutics, Inc., Carisma Therapeutics, Inc., Cytovia Therapeutics, Inc., Fortress Biotech, Inc., Celularity, Inc., Century Therapeutics, Inc., Gamida Cell Ltd., Fate Therapeutics, Inc., In8bio, Inc., Kuur Therapeutics Inc., Lyell Immunopharma, Inc., Nkarta, Inc., Shoreline Bio, 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., 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.

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

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

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.

Future collaborations and mergers and acquisitions may result in further resource concentration among a smaller number of competitors.

Our commercial potential could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive than products that we may develop.

Our commercial potential could be reduced or eliminated if our competitors develop and commercialize products that are better tolerated, more effective, have fewer or less severe side effects, are more convenient or are less expensive than products that we may develop.

Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the market or make our development more complicated.

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

Any agency or judicial enforcement action could have a material adverse effect on us.

We have been placed on clinical hold previously and any future agency or judicial enforcement action could have a material adverse effect on us.

The process required by the FDA before a biological product may be marketed in the United States generally involves the following:

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• performance of adequate and well-controlled human clinical trials according to the FDA’s regulations commonly referred to as good clinical practices (GCPs) and any additional requirements for the protection of human research patients and their health information, to establish the safety and efficacy of the proposed biological product for its intended use;

• submission to the FDA of a BLA for marketing approval that includes substantial evidence of safety, purity, and potency from results of nonclinical testing and clinical trials;

• submission to the FDA of a BLA for marketing approval that includes substantial evidence of safety, purity, and potency from results of nonclinical testing and clinical trials, and which is validated as complete for review by the FDA;

• satisfactory completion of an FDA Advisory Committee review, if applicable;

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Some preclinical testing may continue even after the IND is submitted.

The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA raises concerns or questions regarding the proposed clinical trials and places the trial on a clinical hold within that 30-day time period.

The IND automatically becomes effective 30 days after receipt by the FDA,

unless the FDA raises concerns or questions regarding the proposed clinical trials and places the trial on a clinical hold within that 30-day time period.

In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin.

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Clinical trials involve the administration of the biological product candidate to patients under the supervision of qualified investigators, generally physicians not employed by or under the trial sponsor’s control.

Clinical trials are conducted

under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur.

Clinical trials are conducted under protocols detailing, among other things, the objectives of the clinical trial, dosing procedures, subject selection and exclusion criteria, and the parameters to be used to monitor subject safety, including stopping rules that assure a clinical trial will be stopped if certain adverse events should occur.

Each protocol and any amendments to the protocol must be submitted to the FDA as part of the IND.

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IBCs are typically assigned certain review responsibilities relating to the use of recombinant DNA molecules, including reviewing potential environmental risks, assessing containment levels, and evaluating the adequacy of facilities, personnel training, and compliance with the National Institutes of Health Guidelines.

Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

We may also engage an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, to provide authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration of efficacy.

There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries.

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These clinical trials are intended to establish the overall risk to benefit ratio of the product and provide an adequate basis for product labeling.

Post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be conducted after initial marketing approval.

Long term follow up for all patients who get marketed product and post-approval clinical trials, sometimes referred to as Phase 4 clinical trials, may be required after initial marketing approval.

These clinical trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication, particularly for long-term safety follow-up.

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Data obtained from clinical trials are not always conclusive and the FDA may interpret data differently than we interpret the same data.

If the agency decides not to approve the BLA in its present form, the FDA will issue a complete response letter that describes all of the specific deficiencies in the BLA identified by the FDA.

If the agency decides not to approve the BLA in its

present form, the FDA will issue a complete response letter that describes all of the specific deficiencies in the BLA identified by the FDA.

The deficiencies identified may be minor, for example, requiring labeling changes, or major, for example, requiring additional clinical trials.

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Further, the FDA may require that certain contraindications, warnings or precautions be included in the product labeling.

The FDA may impose restrictions and conditions on product distribution, prescribing, or dispensing in the form of a risk management plan, or

otherwise limit the scope of any approval.

The FDA may impose restrictions and conditions on product distribution, prescribing, or dispensing in the form of a risk management plan, or otherwise limit the scope of any approval.

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

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

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

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

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

Additionally, a product may be eligible for accelerated approval.

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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.

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

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

Post-Approval Requirements

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

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

Manufacturers and other entities involved in the manufacture and

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

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

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

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

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.

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

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

reimbursable under Medicare, Medicaid or other federal healthcare programs.

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

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

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

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

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.

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.

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

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

Even if favorable coverage and reimbursement

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

Healthcare Reform

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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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 eliminated the health insurer tax.

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

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

On December 14, 2018, a Texas U.S.

District Court Judge ruled that the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part of the Tax Act.

Additionally, on December 18, 2019, the U.S.

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.

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.

In December 2018, CMS published a final rule permitting further collections and payments to and from certain Affordable Care

Act qualified health plans and health insurance issuers under the Affordable Care Act risk adjustment program in response to the outcome of federal district court litigation regarding the method CMS uses to determine this risk adjustment.

On June 17, 2021 the U.S.

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

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

Further, prior to the U.S.

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

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

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

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

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

Under current legislation, the actual reduction in Medicare payments will vary from 1% in 2022 to up to 3% in the final fiscal year of this sequester.

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

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

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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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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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.

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

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.

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.

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

California Consumer Privacy Act

California recently enacted legislation, effective January 1, 2020, that has been dubbed the first “GDPR-like” law in the United States.

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

The CCPA requires covered companies to provide new disclosures to California consumers, 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 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.

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

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

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

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

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

Human Capital

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One Allogene Culture

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

We express our culture under the framework of “One Allogene”:

We only succeed as a team.

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In addition, as of February 1, 2022, 66% of all employees were self-reportedly ethnic or racial minorities in the U.S., with 51% Asian, 2% Black or African American, 6% Hispanic or Latino and 7% of other minority groups or two or more races.

Of our Director-level and above employees, 39% were self-reportedly ethnic or racial minorities in the U.S., with 30% Asian, 1% Black or African American, 1% Hispanic or Latino and 6% of other minority groups or two or more races.

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

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

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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.

The DEI Committee and DEI Advisory Board

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

We believe in equal pay for equal work.

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We also 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.

In 2020 and 2021, 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.

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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.

In 2021, we recruited over 115 new employees.

Our average time to hire was less than 70 days and over 80% of candidates accepted our offers.

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

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

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.

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

COVID-19 Employee Safety and Engagement

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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.

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

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

Corporate Information

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

What changed 10-K

Item 1. Business