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What changed in Allogene Therapeutics, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Allogene Therapeutics, Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+637 added−558 removedSource: 10-K (2026-03-12) vs 10-K (2024-12-31)

Top changes in Allogene Therapeutics, Inc.'s 2025 10-K

637 paragraphs added · 558 removed · 434 edited across 7 sections

Item 1. Business

Business — how the company describes what it does

142 edited+70 added−50 removed328 unchanged
Biggest changeMost Prevalent Treatment-Emergent Adverse Events (TEAEs) (>40% Any Grade Incidence) and Adverse Events of Special Interest (AESI) Adverse Event, n(%) All Patients (N=39) DL2 FC500 (N=11) All Grades Grade ≥3 All Grades Grade ≥3 Any TEAE a 39 (100) 29 (81) 11 (100) 8 (73) CRS 24 (62) 1 (3) 8 (73) 0 Fatigue 23 (59) 1 (3) 2 (18) 0 Neutropenia 22 (56) 20 (51) 7 (64) 7 (64) White blood cell count decreased 21/(54) 19 (49) 8 (73) 8 (73) Anemia 20 (51) 13 (33) 7 (64) 5 (46) Nausea 20 (51) 0 3 (27) 0 Thrombocytopenia 18 (46) 10 (26) 7 (64) 3 (27) Pyrexia 16 (41) 2 (5) 4 (36) 0 AEs of Special Interest Any Grade Grade ≥3 Any Grade Grade ≥3 Infection b Viral infections 24 (62) 13 (33) 12 (31) 2 (5) 5 (46) 2 (18) 2 (18) 0 Neurotoxicity c Headache 17 (44) 8 (21) 12 (31) 2 (5) 5 (46) 2 (18) 2 (18) 0 IEC-HS d 5 (13) 1 (3) 2 (18) 0 ICANS 3 (8) 0 3 (27) 0 Graft-versus-host disease 0 0 0 0 a TEAE included all AEs that started from the first dose date of study drug in each treatment period up to start of another treatment period, death, or the date prior to initiation of another anti-cancer agent, whichever occurred first. b Infection events (62%) were primarily low grade; the most common was viral infections (33%) with cytomegalovirus infection and COVID-19 (any grade, 18% and 15%; Grade ≥3, 0% and 5%, respectively). c Neurotoxicity includes system organ class of nerve system disorders and psychiatric disorders with onset date up to Study Day 30 post ALLO-316 infusion. d IEC-HS includes the preferred terms IEC-HS, HLH, Hemophagocytic lymphohistiocytosis, and atypical HLH.
Biggest changeMost Prevalent Treatment-Emergent Adverse Events (TEAEs) (>20% Any Grade Incidence) and Adverse Events of Special Interest (AESI) TEAEs ≥20% incidence in Phase 1b, n (%) Phase 1b (n = 22)† All Grades Grade ≥3 Neutropenia 15 (68) 15 (68) White blood cell count decreased 15 (68) 15 (68) Anemia 13 (59) 9 (41) Thrombocytopenia 12 (55) 6 (27) Nausea 8 (36) 0 ALT increased 7 (32) 2 (9) Peripheral edema 7 (32) 0 Pyrexia 7 (32) 0 Arthralgia 6 (27) 0 AST increased 6 (27) 2 (9) Fatigue 5 (23) 0 Headache 5 (23) 0 AEs of Special Interest Any Grade Grade ≥3 CRS 15 (68) 0 Infection 10 (45) 8 (36) IEC-HS 8 (36) 2 (9)†† ICANS 4 (18) 0 17 Table of Contents Graft-versus-host disease 0 0 IEC-HS includes the preferred terms immune effector cell-associated HLH-like syndrome and Hemophagocytic lymphohistiocytosis. †Includes 2 patients who received lymphodepletion but did not receive ALLO-316 †† One patient experienced G4 IEC-HS based on GI bleeding with subsequent improvement and 1 patient experienced G3 IEC-HS based on hypotension managed without pressors with subsequent improvement.
Our Approach Our allogeneic CAR T cell development strategy has four key pillars: (1) engineering product candidates to minimize the risk of graft-versus-host disease (GvHD), a condition where allogeneic T cells can recognize the patient’s normal tissue as foreign and cause damage, (2) creating a window of persistence that may enable allogeneic T cells to expand and eradicate cancer cells in patients or pathogenic autoreactive cells in patients, (3) building a leading manufacturing platform to enable consistent and high quality production and (4) leveraging next generation technologies to improve the functionality of allogeneic CAR T cells.
Our Approach Our allogeneic CAR T cell development strategy has four key pillars: (1) engineering product candidates to minimize the risk of graft-versus-host disease (GvHD), a condition where allogeneic T cells can recognize the patient’s normal tissue as foreign and cause damage, (2) creating a window of persistence that may enable allogeneic T cells to expand and eradicate cancer cells or pathogenic autoreactive cells in patients, (3) building a leading manufacturing platform to enable consistent and high quality production and (4) leveraging next generation technologies to improve the functionality of allogeneic CAR T cells.
Zachary Roberts, was also instrumental in the development and execution of the clinical trials of Yescarta® across multiple indications. 7 Table of Contents Our Strategy Our goal is to maintain and build upon our leadership position in allogeneic CAR T cell therapy.
Zachary Roberts, was also instrumental in the development and execution of the clinical trials of Yescarta® across multiple indications. Our Strategy 7 Table of Contents Our goal is to maintain and build upon our leadership position in allogeneic CAR T cell therapy.
Our patent portfolio includes protection for our clinical-stage product candidates, ALLO-501, cema-cel, ALLO-316, ALLO-329, ALLO-715, and ALLO-605, as well as our research-stage candidates. With respect to ALLO-501 and cema-cel, we have an exclusive license from Servier to patent rights in the United States covering compositions of matter of and methods of making and using ALLO-501 and cema-cel.
Our patent portfolio includes protection for our clinical-stage product candidates, ALLO-501, cema-cel, ALLO-316, ALLO-329, ALLO-715, and ALLO-605, as well as our research-stage candidates. With respect to cema-cel, we have an exclusive license from Servier to patent rights in the United States covering compositions of matter of and methods of making and using cema-cel.
NHL can be rapidly growing (aggressive), such as LBCLs, or it can be slow growing, or indolent, such as follicular lymphoma (FL). The R-CHOP chemotherapy combination (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) introduced in the early 2000s remains the standard of care for newly diagnosed LBCL, and can yield five-year survival rates of 55-60%.
NHL can be rapidly growing (aggressive), such as LBCLs, or it can be slow growing, or indolent, such as follicular lymphoma (FL). The R-CHOP chemotherapy combination (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), introduced in the early 2000s, remains the standard of care for newly diagnosed LBCL and can yield five-year survival rates of approximately 55-60%.
The ALPHA3 trial will randomize approximately 240 patients who achieve a complete or partial response to 1L therapy, but who test positive for MRD at their end-of-therapy PET/CT assessment. The patients will be randomized to either treatment with cema-cel or the current standard of care, which is observation.
The ALPHA3 trial will randomize approximately 220 patients who achieve a complete or partial response to 1L therapy, but who test positive for MRD at their end-of-therapy PET/CT assessment. The patients will be randomized to either treatment with cema-cel or the current standard of care, which is observation.
Additionally, companies, such as ADC Therapeutics SA, Amgen Inc., Daiichi Sankyo Company, Limited, Gilead Sciences, Inc., GlaxoSmithKline plc, ImmunoGen, Inc., Pfizer 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.
Additionally, companies, such as ADC Therapeutics SA, Amgen Inc., Daiichi Sankyo Company, Limited, Gilead Sciences, Inc., GlaxoSmithKline plc, ImmunoGen, Inc., Pfizer Inc., Regeneron Pharmaceuticals, 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 example, we may experience competition in these markets from companies such as Adicet Bio, Inc., Arcellx, Inc., Atara Biotherapeutics, Inc., Autolus Therapeutics plc, BMS, Cabaletta Bio, Inc., Caribou Biosciences, Inc., Cartesian Therapeutics, Inc., CRISPR Therapeutics AG, Fate Therapeutics, Inc., Gracell Biotechnologies, Inc., ImmPACT Bio USA, Inc., Kyverna Therapeutics, Inc., Nkarta, Inc., Novartis, Sana Biotechology, Inc., and TG Therapeutics Inc.
For example, we may experience competition in these markets from companies such as Adicet Bio, Inc., Arcellx, Inc., Atara Biotherapeutics, Inc., Autolus Therapeutics plc, BMS, Cabaletta Bio, Inc., Caribou Biosciences, Inc., Cartesian Therapeutics, Inc., CRISPR Therapeutics AG, Fate Therapeutics, Inc., Gracell Biotechnologies, Inc., ImmPACT Bio USA, Inc., Kyverna Therapeutics, Inc., Nkarta, Inc., Novartis, Sana Biotechnology, Inc., and TG Therapeutics Inc.
The figure below shows the constructs that support our lead product candidates in clinical development: cema-cel, ALLO-316 and ALLO-329. Allogeneic CAR T Cell Products: The Next Revolution There are two primary approaches to engineered T cell therapy: autologous and allogeneic.
The figure below shows the constructs that support our lead product candidates in clinical development: cema-cel, ALLO-316 and ALLO-329. Allogeneic CAR T Cell Products: The Next Revolution There are two primary ex vivo approaches to engineered T cell therapy: autologous and allogeneic.
If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years, except in limited 26 Table of Contents circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.
If a product that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications, including a full BLA, to market the same biologic for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity.
The primary intent of the GTP requirements is to ensure that cell and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission and spread of communicable disease. FDA regulations also require tissue establishments to register and list their HCT/Ps with the FDA and, when applicable, to evaluate donors through screening and testing.
The primary intent of the GTP requirements is to ensure that cell and tissue-based products are manufactured in a manner designed to prevent the introduction, 26 Table of Contents transmission and spread of communicable disease. FDA regulations also require tissue establishments to register and list their HCT/Ps with the FDA and, when applicable, to evaluate donors through screening and testing.
We encourage our employees to participate 36 Table of Contents and take advantage of a variety of learning and development resources, including online business skills courses, professional development events, and external training programs based on individual needs. We also actively review employee performance and business needs every six months that lead to promotional opportunities for employees across departments and levels.
We encourage our employees to participate and take advantage of a variety of learning and development resources, including online business skills courses, professional development events, and external training programs based on individual needs. We also actively review employee performance and business needs every six months that lead to promotional opportunities for employees across departments and levels.
There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries. 24 Table of Contents Human clinical trials are typically conducted in three sequential phases that may overlap or be combined: • Phase 1. The biological product is initially introduced into healthy human subjects and tested for safety.
There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries. Human clinical trials are typically conducted in three sequential phases that may overlap or be combined: • Phase 1. The biological product is initially introduced into healthy human subjects and tested for safety.
For example, pharmaceutical and other healthcare companies have 30 Table of Contents been, and continue to be, investigated or prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product and for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-reimbursable, uses.
For example, pharmaceutical and other healthcare companies have been, and continue to be, investigated or prosecuted under these laws for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product and for causing false claims to be submitted because of the companies’ marketing of the product for unapproved, and thus non-reimbursable, uses.
Additional Regulation In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business.
Additional Regulation In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act and the Toxic Substances Control Act, affect our business.
See the section titled “Risk Factors – Risks Related to Our Business and Industry” and “Risk Factors – Risks Related to Government Regulation” for additional information about the laws and regulations to which we may become subject and about the risks to our business associated with such laws and regulations.
Refer to the section titled “Risk Factors – Risks Related to Our Business and Industry” and “Risk Factors – Risks Related to Government Regulation” for additional information about the laws and regulations to which we may become subject and about the risks to our business associated with such laws and regulations.
In addition, quality control and manufacturing procedures must continue to conform to applicable manufacturing requirements after approval to ensure the long-term stability of the product. 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.
In addition, quality control and manufacturing procedures must continue to conform to applicable manufacturing requirements after approval to ensure the long-term stability of the product. cGMP regulations require among other things, 28 Table of Contents 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.
Information contained on or accessible through our website is not a part of this report, and the inclusion of our website address in this report is an inactive textual reference only. 37 Table of Contents
Information contained on or accessible through our website is not a part of this report, and the inclusion of our website address in this report is an inactive textual reference only. 38 Table of Contents
Additionally, in February 2025, we entered into an Amended and Restated Strategic Collaboration Agreement with Foresight Diagnostics which expands our collaboration to enable the development of Foresight Diagnostics’ MRD assay as a companion diagnostic in the EU, UK, Canada and Australia in support of Allogene’s clinical development of cema-cel.
In February 2025, we entered into an Amended and Restated Strategic Collaboration Agreement with Foresight Diagnostics which expands our collaboration to enable the development of Foresight Diagnostics’ CLARITY TM MRD assay as a companion diagnostic in the EU, UK, Canada and Australia in support of Allogene’s clinical development of cema-cel.
Chimeric Antigen Receptors (CARs) CARs are engineered molecules that, when present on the surface of a T cell, enable the T cell to recognize specific proteins or antigens that are present on the surface of other cells. More than one type of CAR can be included in a CAR T cell, 8 Table of Contents imparting multi-antigen targeting capability.
Chimeric Antigen Receptors (CARs) CARs are engineered molecules that, when present on the surface of a T cell, enable the T cell to recognize specific proteins or antigens that are present on the surface of other cells. More than one type of CAR can be included in a CAR T cell, imparting multi-antigen targeting capability.
The anti-rejection features of ALLO-329 may help reduce or eliminate the need for lymphodepletion prior to treatment with ALLO-329. 18 Table of Contents Lead Target Indications: Systemic Lupus Erythematosus (SLE), Lupus Nephritis, Idiopathic Inflammatory Myopathies, and Systemic Sclerosis In January 2025 we announced that the FDA has cleared our IND for a rheumatology basket study of ALLO-329.
The anti-rejection features of ALLO-329 may help reduce or eliminate the need for lymphodepletion prior to treatment with ALLO-329. 18 Table of Contents Lead Target Indications: Systemic Lupus Erythematosus (SLE), Lupus Nephritis, Idiopathic Inflammatory Myopathies, and Systemic Sclerosis In January 2025 we announced that the FDA had cleared our IND for a rheumatology basket study of ALLO-329, which we initiated in 2025.
The target binding domain consists of a single-chain variable fragment (scFv) of an antibody comprising variable domains of heavy and light chains joined by a short linker. • Transmembrane Domain and Hinge: This middle portion of the CAR links the scFv target binding domain to the activating elements inside the cell.
The target 8 Table of Contents binding domain consists of a single-chain variable fragment (scFv) of an antibody comprising variable domains of heavy and light chains joined by a short linker. • Transmembrane Domain and Hinge: This middle portion of the CAR links the scFv target binding domain to the activating elements inside the cell.
The ALPHA3 trial is an open-label, Phase 2, multicenter clinical trial evaluating the safety and efficacy of cema-cel in adult patients with LBCL who have completed R-CHOP and have attained a remission, but who test positive for MRD.
The ALPHA3 trial is an open-label, Phase 2, multicenter clinical trial evaluating the safety and efficacy of cema-cel in adult patients with LBCL who have completed R-CHOP for other standard regimen and have attained a remission, but who test positive for MRD.
Under the License Amendment, we continue to grant Allogene Overland PRC an exclusive license to develop, manufacture, and commercialize the JV Licensed Products in the JV Territory, with us retaining exclusive rights to the JV Licensed Products outside the JV Territory We have also entered into multiple additional strategic agreements and collaborations, including an Asset Contribution Agreement with Pfizer (the Pfizer Agreement), a License Agreement with Cellectis (the Cellectis Agreement), the Servier Agreement, a Collaboration and License Agreement (the Notch Agreement) with Notch Therapeutics Inc.
Under the License Amendment, we continue to grant Allogene Overland PRC an exclusive license to develop, manufacture, and commercialize the JV Licensed Products in the JV Territory, with us retaining exclusive rights to the JV Licensed Products outside the JV Territory We have also entered into multiple additional strategic agreements and collaborations, including an Asset Contribution Agreement with Pfizer (the Pfizer Agreement), a License Agreement with Cellectis (the Cellectis Agreement), the Servier 20 Table of Contents Agreement, a Collaboration and License Agreement (the Notch Agreement) with Notch Therapeutics Inc.
Before testing any biological product candidate, including our product candidates, in humans, the product candidate enters the preclinical testing stage. Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the product candidate.
Before testing any biological product candidate, including our product candidates, in humans, the product candidate enters the preclinical testing stage. Preclinical tests, also referred to as nonclinical studies, include laboratory evaluations of 24 Table of Contents product chemistry, toxicity and formulation, as well as animal studies to assess the potential safety and activity of the product candidate.
The FDA categorizes human cell- or tissue-based products as either minimally manipulated or more than minimally manipulated, and has determined that more than minimally manipulated products require clinical trials to demonstrate product safety and efficacy and the submission of a BLA for marketing authorization.
The FDA categorizes human cell- or tissue-based products as either minimally manipulated or more than minimally manipulated, and has determined that more than minimally manipulated products require clinical trials to demonstrate product safety and efficacy and the submission of a biologics license application (BLA) for marketing authorization.
If the FDA’s evaluation of the PMA application is favorable, the FDA typically issues an approvable letter requiring the applicant’s agreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to 29 Table of Contents secure final approval of the PMA.
If the FDA’s evaluation of the PMA application is favorable, the FDA typically issues an approvable letter requiring the applicant’s agreement to specific conditions, such as changes in labeling, or specific additional information, such as submission of final labeling, in order to secure final approval of the PMA.
As discussed in more detail below, these limitations become increasingly prohibitive in diseases where time is of the essence as is the case in 1L consolidation, making autologous CAR T therapy unsuitable for such use. 9 Table of Contents • Variable Potency .
As discussed in more detail below, these limitations become increasingly prohibitive in diseases where time is of the essence as is the case in 1L consolidation, making autologous CAR T therapy unsuitable for such use. • Variable Potency .
A patent term extension under the Hatch-Waxman Act cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent applicable to an approved drug may be extended.
A patent term extension under the Hatch-Waxman Act cannot extend the remaining term of a patent beyond a total of 14 years from the date 21 Table of Contents of product approval and only one patent applicable to an approved drug may be extended.
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (HITECH) and their implementing regulations, imposes requirements on certain types of individuals and entities relating to the privacy, security and transmission of individually identifiable health information.
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act 31 Table of Contents (HITECH) and their implementing regulations, imposes requirements on certain types of individuals and entities relating to the privacy, security and transmission of individually identifiable health information.
In addition, the individualized nature of autologous manufacturing, together with the variability in patients’ T cells, may lead to variable potency of manufactured T cells, and this variability may cause unpredictable treatment outcomes. • Manufacturing Failures . Autologous cell manufacturing sometimes encounters production failures.
In addition, the individualized nature of autologous manufacturing, together with the variability in patients’ T cells, may lead to variable potency of manufactured T cells, and this variability may cause unpredictable treatment outcomes. 9 Table of Contents • Manufacturing Failures . Autologous cell manufacturing sometimes encounters production failures.
The review of in vitro companion diagnostics in conjunction with the review of our product candidates in development for cancer will, therefore, likely involve coordination of review by the FDA’s Center for Drug Evaluation and Research and the FDA’s Center for Devices and Radiological Health Office of In Vitro Diagnostics and Radiological Health.
The review of in vitro 29 Table of Contents companion diagnostics in conjunction with the review of our product candidates in development for cancer will, therefore, likely involve coordination of review by the FDA’s Center for Drug Evaluation and Research and the FDA’s Center for Devices and Radiological Health Office of In Vitro Diagnostics and Radiological Health.
The FDA or the sponsor or its data safety monitoring board may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research patients are being exposed to an unacceptable health risk, including risks inferred from other unrelated immunotherapy trials.
The FDA or the sponsor or its data safety monitoring board may suspend or terminate a clinical trial at any time on various 25 Table of Contents grounds, including a finding that the research patients are being exposed to an unacceptable health risk, including risks inferred from other unrelated immunotherapy trials.
The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, potent, and/or effective for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP to assure and 25 Table of Contents preserve the product’s identity, safety, strength, quality, potency and purity.
The FDA reviews the BLA to determine, among other things, whether the proposed product is safe, potent, and/or effective for its intended use, and has an acceptable purity profile, and whether the product is being manufactured in accordance with cGMP to assure and preserve the product’s identity, safety, strength, quality, potency and purity.
The EU GDPR regulations may impose additional responsibility and liability in relation to the personal data that we process and we may be required to put in place additional mechanisms to ensure compliance with the new data protection rules. 34 Table of Contents Additionally, numerous US states have passed comprehensive privacy laws.
The EU GDPR regulations may impose additional responsibility and liability in relation to the personal data that we process and we may be required to put in place additional mechanisms to ensure compliance with the new data protection rules. Additionally, numerous US states have passed comprehensive privacy laws.
Competition 21 Table of Contents Oncology is a highly competitive market for drug development. If successfully developed, our products will compete with therapies that have been developed or are in development at biopharmaceutical companies, academic research institutions, governmental agencies and public and private research institutions.
Competition Oncology is a highly competitive market for drug development. If successfully developed, our products will compete with therapies that have been developed or are in development at biopharmaceutical companies, academic research institutions, governmental agencies and public and private research institutions.
We plan to continue to advance the research and development of ALLO-316, which targets CD70, for the treatment of clear cell renal cell carcinoma (ccRCC) as part of our TRAVERSE trial. We are investigating next-generation technologies incorporated in the design of ALLO-316 which seek to better control rejection of allogeneic CAR T cells by the patient's immune system.
We plan to continue to advance the research and development of ALLO-316, which targets CD70, for the treatment of clear cell renal cell carcinoma (ccRCC). We are investigating next-generation technologies incorporated in the design of ALLO-316 which seek to better control rejection of allogeneic CAR T cells by the patient's immune system.
We have exclusive worldwide rights to these patents for certain antigen targets, including BCMA, CD70, FLT3, DLL3 and Claudin 18.2, and have U.S., EU, and UK rights to these patents for CD19.
We have exclusive worldwide rights to these patents for certain antigen targets, including BCMA, CD70, FLT3, DLL3 and Claudin 18.2, and have U.S., EU, and UK rights to these patents for cema-cel.
We 33 Table of Contents believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations.
We believe that we are in material compliance with applicable environmental laws and that continued compliance therewith will not have a material adverse effect on our business. We cannot predict, however, how changes in these laws may affect our future operations.
For instance, we may experience competition from companies, such as AbbVie, Inc., Amgen Inc., BMS, Compass Therapeutics, Inc., F. Hoffmann-La Roche 22 Table of Contents AG, Genmab A/S, GlaxoSmithKline plc, Immunocore Holdings plc, Johnson & Johnson, MacroGenics, Inc., Merck & Co.
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, Immunocore Holdings plc, Johnson & Johnson, MacroGenics, Inc., Merck & Co.
Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. Different pricing and reimbursement schemes exist in other countries.
Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. 32 Table of Contents Different pricing and reimbursement schemes exist in other countries.
(Notch), a License and Collaboration Agreement with Antion, and a Strategic Collaboration Agreement with Foresight Diagnostics. For additional information regarding our significant agreements, see Note 6 to our consolidated financial statements appearing elsewhere in this Annual Report.
(Notch), and a Strategic Collaboration Agreement with Foresight Diagnostics. For additional information regarding our significant agreements refer to Note 6 in our consolidated financial statements appearing elsewhere in this Annual Report.
Our most advanced product candidate, cemacabtagene ansegedleucel, referred to as cema-cel (previously ALLO-501A), is an engineered allogeneic CAR T cell product candidate that targets CD19, a protein expressed on the cell surface of B cells and a validated target for B cell driven hematological malignancies. We are currently focused on developing cema-cel for LBCL.
Our most advanced product candidate, cemacabtagene ansegedleucel, referred to as cema-cel (previously ALLO-501A), is an engineered allogeneic CAR T cell product candidate that targets CD19, a protein expressed on the cell surface of B cells and a validated target for B cell-derived hematological malignancies. We are currently focused on developing cema-cel for LBCL. Our pipeline also includes ALLO-316 and ALLO-329.
The ALPHA3 trial was initiated in June 2024 and now has 40 sites activated and screening for patients with MRD.
The ALPHA3 trial was initiated in June 2024 and now has over 60 sites activated and screening for patients with MRD.
Five of 12 patients in this group achieved CR that lasted at least 6 months. 13 Table of Contents Patients Treated with Phase 2 Regimen (n=12) Overall Response Rate (ORR), n (%) 8 (67) Complete Response (CR), n (%) 7 (58) 6 Month CR Rate, n (%) 5 (42) Patients who achieved a CR had excellent outcomes with a median DOR, PFS (progression free survival) and OS of 23.1 months, 24 months, and not reached, respectively.
Patients Treated with Phase 2 Regimen (n=12) 13 Table of Contents Overall Response Rate (ORR), n (%) 8 (67) Complete Response (CR), n (%) 7 (58) 6 Month CR Rate, n (%) 5 (42) Patients who achieved a CR had excellent outcomes with a median DOR, PFS (progression free survival) and OS of 23.1 months, 24 months, and not reached, respectively.
Allogeneic engineered T cells are manufactured in a similar manner as autologous, but our manufacturing has two key differences: (1) our allogeneic T cells are derived from healthy donors, not cancer patients, and (2) our allogeneic T cells are genetically engineered to minimize the risk of GvHD and enable a window of persistence in the patient.
Allogeneic engineered T cells are manufactured in a similar manner as autologous, but our manufacturing has two key differences: (1) our allogeneic T cells are derived from healthy donors, not the patients themselves, and (2) our allogeneic T cells are genetically engineered to minimize the risk of GvHD.
As we advance those programs, we may seek to utilize our allogeneic platform to pursue additional targets of interest, particularly through strategic partnerships. These include the additional targets currently in our pipeline as well as other targets that might be validated in the future.
As we advance those programs, we may seek to utilize our allogeneic platform to pursue additional targets of interest, particularly through strategic partnerships. These include the additional targets currently in our pipeline as well as other targets that might be validated in the future, either of which we may seek to combine with our Dagger® technology.
We also have patent rights to the TurboCAR™ technology solely owned by us, including technology that covers the TurboCAR™ construct that is part of ALLO-605.
We also have patent rights to the TurboCAR™ and Dagger ® technologies solely owned by us, including technology that covers the TurboCAR™ construct that is part of ALLO-605, and the Dagger ® construct that is part of ALLO-329.
Renal Cell Carcinoma (RCC) : TRAVERSE trial with ALLO-316 seeks to advance scientific innovation underlying the Dagger® technology to optimize CAR T cell expansion and persistence, thereby maximizing the potential of allogeneic CAR T in solid tumors while mitigating treatment-associated inflammatory response.
Renal Cell Carcinoma (RCC) : TRAVERSE trial with ALLO-316 seeks to advance scientific innovation underlying the Dagger® technology to optimize CAR T cell expansion and persistence, thereby maximizing the potential of allogeneic CAR T in solid tumors.
In the United States, third-party payors include federal and state 31 Table of Contents healthcare programs, private managed care providers, health insurers and other organizations.
In the United States, third-party payors include federal and state healthcare programs, private managed care providers, health insurers and other organizations.
The RMAT designation was based on Phase 1 clinical data from the TRAVERSE trial indicating the potential of ALLO-316 to address the unmet need for patients with difficult-to-treat RCC who have failed multiple standard RCC therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.
The RMAT designation was based on Phase 1 clinical data from the TRAVERSE trial indicating the potential of ALLO-316 to address the unmet need for patients with difficult-to-treat RCC who have failed multiple standard RCC therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy. We are currently exploring partnering opportunities to advance the asset. • ALLO-329.
Although we are currently focusing on our three core development programs noted above, we continue to have a deep pipeline to further the research and development of allogeneic CAR T cell product candidates in both hematological malignancies and solid tumors.
Although we are currently focusing on our three core development programs noted above, we continue to build a pipeline to further the research and development of allogeneic CAR T cell product candidates in both hematological malignancies and solid tumors, as well as in autoimmune diseases.
We have also sponsored the EXPAND trial of ALLO-647, which was intended to demonstrate the overall contribution of ALLO-647 to the benefit to risk ratio of the lymphodepletion regimen for cema-cel.
We are the sponsor of the EXPAND trial of ALLO-647, which was intended to demonstrate the overall contribution of ALLO-647 to the risk-benefit ratio of the lymphodepletion regimen for cema-cel.
ALLO-316 is manufactured to express a CAR that is designed to target CD70 and gene edited to lack expression of the TCR and CD52 to both minimize the risk of GvHD and to enable use of CD52 monoclonal antibodies to permit a window of persistence of CAR T cells in the patient.
ALLO-316 is manufactured to express a CAR that is designed to target CD70 and gene edited to lack expression of the TCR to minimize the risk of GvHD. We also inactivated CD52, which was intended to enable use of CD52 monoclonal antibodies to potentially permit a window of persistence of CAR T cells in the patient.
Pediatric exclusivity, if granted, adds six months to existing exclusivity periods and patent terms. This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.
This six-month exclusivity, which runs from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric trial in accordance with an FDA-issued “Written Request” for such a trial.
For our oncology programs we use Cellectis, S.A. (Cellectis), TALEN® gene-editing technology to limit the risk of GvHD by engineering T cells to lack functional T cell receptors (TCRs), thereby preventing them from recognizing a patient’s normal tissue as foreign.
We use Cellectis, S.A. (Cellectis), TALEN® gene-editing technology and Arbor Biotechnologies CRISPR-based gene-editing technology in our oncology and autoimmune programs, respectively, to limit the risk of GvHD by engineering T cells to lack functional T cell receptors (TCRs), thereby preventing them from recognizing a patient’s normal tissue as foreign.
Assuming favorable outcomes and subject to FDA discussions, we plan to seek FDA approval of cema-cel, and possibly ALLO-647, based on the ALPHA3 trial. Additionally, assuming favorable outcomes, we anticipate that the ALPHA3 data set could be used to support EU regulatory approval.
Assuming favorable outcomes and subject to FDA discussions, we plan to seek FDA approval of cema-cel based on the ALPHA3 trial. Additionally, assuming favorable outcomes, we anticipate that the ALPHA3 data set could be used to support EU regulatory approval regardless of whether the ALPHA3 trial is expanded into the EU.
Our pipeline also includes ALLO-316 and ALLO-329. ALLO-316 is an engineered allogeneic CAR T cell product candidate that targets CD70, which is highly expressed in RCC and is selectively expressed in several other cancers thereby creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors.
ALLO-316 is an engineered allogeneic CAR T cell product candidate that targets CD70, which is highly expressed in RCC and is selectively expressed in several other cancers thereby creating the potential for ALLO-316 to be developed across a variety of both hematologic malignancies and solid tumors. We are currently focused on developing ALLO-316 for RCC.
Following the clearance of an IND in January 2025, we plan to initiate a Phase 1 clinical trial (the RESOLUTION trial) of ALLO-329, an allogeneic CAR T cell product candidate targeting both CD19 and CD70, in adult patients with systemic lupus erythematosus, including lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis in mid-2025.
During 2025, we initiated a Phase 1 clinical trial (the RESOLUTION trial) of ALLO-329, an allogeneic CAR T cell product candidate targeting both CD19 and CD70, in adult patients with systemic lupus erythematosus, including lupus nephritis, idiopathic inflammatory myopathies, and systemic sclerosis.
A retrospective analysis of patients with R/R LBCL, 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: 18%) and median overall survival of 6.3 months.
A retrospective analysis of patients with R/R LBCL, who were not treated with autologous CAR T therapy reported an objective response rate of 26% (complete response (CR): 7%, partial response: 18%) and median overall survival of 6.3 months.
Corporate Information We were incorporated in Delaware in November 2017. Our principal executive offices are located at 210 East Grand Avenue, South San Francisco, California 94080, and our telephone number is (650) 457-2700. Our corporate website address is www.allogene.com.
Our principal executive offices are located at 210 East Grand Avenue, South San Francisco, California 94080, and our telephone number is (650) 457-2700. Our corporate website address is www.allogene.com.
We have built our own current good manufacturing practices (cGMP) manufacturing facility in Newark, California, that we call Cell Forge 1 (CF1). We are currently utilizing CF1 for clinical manufacturing of our product candidates.
We have built our own current good manufacturing practices (cGMP) manufacturing facility in Newark, California, that we call Cell Forge 1 (CF1). We exclusively utilize CF1 for manufacturing of our product candidates for use in clinical studies.
In the future, we may intend to apply for restoration of patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA. 28 Table of Contents Pediatric exclusivity is another type of regulatory market exclusivity in the United States.
In the future, we may intend to apply for restoration of patent term for one of our currently owned or licensed patents to add patent life beyond its current expiration date, depending on the expected length of the clinical trials and other factors involved in the filing of the relevant BLA.
We are currently developing a next-generation product candidate, ALLO-329, which is an engineered allogeneic CAR T cell product candidate that targets CD19 and CD70. ALLO-329 incorporates our Dagger® technology. In January 2025, we announced that the FDA has cleared our IND for a rheumatology basket study of ALLO-329, our RESOLUTION trial.
We are currently developing a next-generation product candidate, ALLO-329, which is an engineered allogeneic CAR T cell product candidate that targets CD19 and CD70. ALLO-329 incorporates our Dagger® technology. During 2025 we initiated a rheumatology basket study of ALLO-329, our RESOLUTION trial.
Results from the Phase 1 ALLO-316 TRAVERSE Trial On November 7, 2024, we announced interim results from the Phase 1 TRAVERSE trial of ALLO-316 in patients with advanced or metastatic RCC who have progressed on or who are intolerant to standard therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.
Results from the Phase 1 ALLO-316 TRAVERSE Trial On June 1, 2025, we announced updated data from the Phase 1 TRAVERSE trial of ALLO-316 in patients with advanced or metastatic RCC whose tumors had progressed on or who are intolerant to standard therapies, including an immune checkpoint inhibitor and a VEGF-targeting therapy.
Breakthrough therapy designation comes with all of the benefits of fast track designation, which means that the sponsor may file sections of the BLA for review on a rolling basis if certain conditions are satisfied, including an agreement with FDA on the proposed schedule for submission of portions of the application and the payment of applicable user fees before the FDA may initiate a review. 27 Table of Contents 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.
Breakthrough therapy designation comes with all of the benefits of fast track designation, which means that the sponsor may file sections of the BLA for review on a rolling basis if certain conditions are satisfied, including an agreement with FDA on the proposed schedule for submission of portions of the application and the payment of applicable user fees before the FDA may initiate a review.
Under the current standard of care, there is no way to determine which patients are at greater risk of relapse after initially responding to 1L treatment, and so the standard of care has been simply to “watch and wait” for the disease to relapse. Foresight Diagnostics, however, has developed a liquid biopsy testing platform for the measurement of MRD.
Under the current standard of care, there is no way to determine which patients are at greater risk of relapse after initially responding to 1L treatment, and so the standard of care has been simply to “watch and wait” for the disease to relapse.
We do not, however, believe that autologous CAR T therapy will be a viable option in the 1L consolidation setting because of the lengthy lead time for the individualized manufacturing process for autologous CAR T.
We do not, however, believe that autologous CAR T therapy will be a viable option in the 1L consolidation setting because of the reduced T cell counts in patients who have recently completed 1L therapy as well as lengthy lead time for the individualized manufacturing process for autologous CAR T.
A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which cover the methods and documentation of the design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices. Domestic facility records and manufacturing processes are subject to periodic unscheduled inspections by the FDA.
A medical device manufacturer’s manufacturing processes and those of its suppliers are required to comply with the applicable portions of the QSR, which cover the methods and documentation of the 30 Table of Contents design, testing, production, processes, controls, quality assurance, labeling, packaging and shipping of medical devices.
Cema-cel’s Phase 1 safety profile, with low rates of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), already permits its use in the outpatient setting in R/R patients and may further improve in patients with no radiological evidence of disease. The ALPHA3 trial was initiated in 2024 and enrollment is currently ongoing with 40 sites activated in the United States.
Cema-cel’s Phase 1 safety profile, with low rates of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS), already permits its use in the outpatient setting in R/R patients and may further improve in patients with no radiological evidence of disease.
Inclusion of an anti-CD70 CAR in ALLO-329 is designed to reduce or eliminate the need for standard chemotherapy by preventing premature rejection while also targeting CD70+ activated lymphocytes, which may play a direct role in AID pathogenesis.
Inclusion of an anti-CD70 CAR in ALLO-329 is designed to reduce or eliminate the need for standard chemotherapy by preventing premature rejection while also targeting CD70+ activated lymphocytes, which may play a direct role in AID pathogenesis. The Phase 1 RESOLUTION trial is a 3+3 dose-escalation study enrolling patients across SLE, IIMs, and SSc.
As a result, we believe that disruption of the B cell-T cell network could lead to an effective treatment of AIDs. As noted above, CD19 is an antigen expressed on the surface of B cells, including pathogenic autoreactive B cells. Activated T cells, which upregulate CD70, induce sustained production of autoantibodies by B cells from patients affected by AID.
As a result, we believe that disruption of the B cell-T cell network could lead to an effective treatment of AIDs. As noted above, CD19 is an antigen expressed on the surface of B cells, including pathogenic autoreactive B cells.
For example, we have been developing allogeneic CAR T cell product candidates targeting B-cell maturation antigen (BCMA) for treatment of multiple myeloma (ALLO-715), FLT3 for the treatment of acute myeloid leukemia (ALLO-819), DLL3 for the treatment of small cell lung cancer (ALLO-213), and Claudin 18.2 for the treatment of gastric and pancreatic cancer (ALLO-182). 19 Table of Contents Our Manufacturing Strategy We have invested resources to optimize our manufacturing process, including the development of improved analytical methods and instrumentation.
For example, we have been developing allogeneic CAR T cell product candidates targeting B-cell maturation antigen (BCMA) for treatment of multiple myeloma (ALLO-715), FLT3 for the treatment of acute myeloid leukemia (ALLO-819), DLL3 for the treatment of small cell lung cancer (ALLO-213), and Claudin 18.2 for the treatment of gastric and pancreatic cancer (ALLO-182).
In March 2021, BMS and partner 2seventy bio, Inc. received FDA approval of Abecma®, an anti-BCMA autologous T cell therapy, for the treatment of adult patients with multiple myeloma who have received at least four prior therapies. Jannsen and partner Legend Bio received approval for Carvykti®, an anti-BCMA autologous T cell therapy, for the same indication in February 2022.
Autologous cell therapies directed at BCMA have been commercialized by BMS and Janssen, a Johnson & Johnson company. In March 2021, BMS and partner 2seventy bio, Inc. received FDA approval of Abecma®, an anti-BCMA autologous T cell therapy, for the treatment of adult patients with multiple myeloma who have received at least four prior therapies.
Intellectual Property 20 Table of Contents Our commercial success depends in part on our ability to obtain and maintain proprietary protection for our product candidates, as well as novel discoveries, product development technologies, and know-how.
Intellectual Property Our commercial success depends in part on our ability to obtain and maintain proprietary protection for our product candidates, as well as novel discoveries, product development technologies, and know-how. Our commercial success also depends in part on our ability to operate without infringing on the proprietary rights of others and to prevent others from infringing our proprietary rights.
The selected Phase 2 regimen (fludarabine/cyclophosphamide lymphodepletion with 90 mg of ALLO-647 (FCA90) followed by a single dose of CAR+ cells) yielded the highest ORR and CR of 67% and 58%, respectively.
The selected Phase 2 regimen (fludarabine/cyclophosphamide lymphodepletion with 90 mg of ALLO-647 (FCA90) followed by a single dose of CAR+ cells) yielded the highest ORR and CR of 67% and 58%, respectively. Five of 12 patients in this group achieved CR that lasted at least 6 months.
Moreover, CD70 expression is elevated on T cells of patients in certain AIDs, suggesting a pathogenic role for CD70+ T cells in AID. Accordingly, we believe progressing allogeneic CAR T cell therapies directed against CD19 and CD70 could be promising in AID indications. ALLO-329 is manufactured to express two independent CARs designed to target CD19 and CD70.
Accordingly, we believe progressing allogeneic CAR T cell therapies directed against CD19 and CD70 could be promising in AID indications. ALLO-329 is manufactured to express two independent CARs designed to target CD19 and CD70.
Additionally, on March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024. 32 Table of Contents Additionally, there has been increasing legislative and enforcement interest in the United States with respect to specialty drug pricing practices.
Additionally, on March 11, 2021, the American Rescue Plan Act of 2021 was signed into law, which eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024.
We believe a critical component to our success will be to leverage and expand our proprietary manufacturing know-how, expertise and capacity. For instance, for our lead product candidate, cema-cel, we were able to identify and select a manufacturing process that was associated with robust clinical performance in Phase 1.
For instance, for our lead product candidate, cema-cel, we were able to identify and select a manufacturing process that was associated with robust clinical performance in Phase 1.
Based on Foresight Diagnostics’ published data, we believe that the Foresight Diagnostics’ assay is highly sensitive and predictive of which patients are likely to relapse. By incorporating the Foresight Diagnostics assay into our ALPHA3 trial design, we believe that we can identify the patient population most at risk for relapse and treat those patients with cema-cel.
By incorporating the Foresight Diagnostics assay into our ALPHA3 trial design, we believe that we can identify the patient population most at risk for relapse and treat those patients with cema-cel.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

214 edited+103 added−48 removed489 unchanged
Biggest changeIf Roche obtains an injunction or otherwise prevails in its lawsuits, we may be required to seek alternative means for gaining access to the PhasED-Seq MRD assay or find an alternative MRD assay to use in the ALPHA3 trial, either of which may not be available to us on commercially reasonable terms or at all, and/or could significantly delay or prevent the completion of the trial or our plans to commercialize cema-cel as part of a 1L consolidation strategy, if approved, which could materially adversely affect our business, operating results and financial condition.
Biggest changeAlthough Foresight announced on August 29, 2025 that it had entered into a limited licensing agreement with the Roche Parties related to Foresight’s patented PhasED-Seq™ technology, and that the agreement closes the litigation between the parties, with all claims against Foresight, its founders, and Stanford University dismissed with prejudice, if such settlement had not been entered into we may have been required to seek alternative means for gaining access to the PhasED-Seq MRD assay or find an alternative MRD assay to use in the ALPHA3 trial, either of which may not have been available to us on commercially reasonable terms or at all, and/or could have significantly delayed or prevented the completion of the trial or our plans to commercialize cema-cel as part of a 1L consolidation strategy, if approved, which could have materially adversely affected our business, operating results and financial condition.
Unremediated high risk or critical vulnerabilities pose material risks to our business that may be exploited and could result in a security incident. Further, we have experienced and may in the future experience delays in developing and deploying remedial measures designed to address any such identified vulnerabilities.
Unremediated high risk or critical vulnerabilities pose material risks to our business that may be exploited and could result in a security incident. Further, we have experienced and may in the future experience delays in developing and deploying remedial measures designed to address any such identified vulnerabilities. Vulnerabilities could be exploited and result in a security incident.
For our oncology product candidates, we use Cellectis’ TALEN gene-editing technology to inactivate a gene coding for TCRα, a key component of the natural antigen receptor of T cells, to cause the engineered T cells to be incapable of recognizing foreign antigens.
For our oncology product candidates, we use Cellectis’ TALEN gene-editing technology to inactivate the gene coding for TCRα, a key component of the natural antigen receptor of T cells, to cause the engineered T cells to be incapable of recognizing foreign antigens.
If, for any reason, we are unable to continue manufacturing our product candidates at CF1, there is a risk that we may need to re-engage our CDMO to manufacture material, which would be costly and there is a risk that the CDMO may be unavailable or may fail in manufacturing, such as due to the CDMO having to retrain its personnel, or train new personnel, to manufacture our material.
If, for any reason, we are unable to continue manufacturing our product candidates at CF1, there is a risk that we may need to re-engage a CDMO to manufacture material, which would be costly and there is a risk that the CDMO may be unavailable or may fail in manufacturing, such as due to the CDMO having to retrain its personnel, or train new personnel, to manufacture our material.
We have previously experienced a delay in our clinical trials due to a clinical hold, and may experience future delays in completing planned clinical trials for a variety of reasons, including delays related to: • obtaining regulatory authorization to begin a trial, if applicable, including regulatory approval of any companion diagnostic, if applicable; • the availability of financial resources to commence and complete the planned trials; • reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • developing and implementing processes and procedures with collaborators relating to the collection and transfer of patient samples and the timely performance of a companion diagnostic on such samples; • obtaining approval at each clinical trial site by an independent IRB or a positive opinion from an Ethics Committee; • obtaining regulatory and other approvals to modify the conduct of a clinical trial; • recruiting suitable patients to participate in a trial; • delays by a collaboration partner in running a companion diagnostic on patient samples; • having patients complete a trial, including having patients enrolled in clinical trials dropping out of the trial prior to treatment, or return for post-treatment follow-up; • clinical trial sites deviating from trial protocol or dropping out of a trial; • addressing any patient safety concerns that arise during the course of a trial; • adding new clinical trial sites; or • manufacturing sufficient quantities of qualified materials under cGMPs, releasing product in accordance with specifications, and delivering product candidates for use in clinical trials.
We have previously experienced a delay in our clinical trials due to a clinical hold, and may experience future delays in completing planned clinical trials for a variety of reasons, including delays related to: • obtaining regulatory authorization to begin a trial, if applicable, including regulatory approval of any companion diagnostic, if applicable; • the availability of financial resources to commence and complete the planned trials; • reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; • developing and implementing processes and procedures with collaborators relating to the collection and transfer of patient samples and the timely performance of a companion diagnostic, if applicable, on such samples; • obtaining approval at each clinical trial site by an independent IRB or a positive opinion from an Ethics Committee; • obtaining regulatory and other approvals to modify the conduct of a clinical trial; • recruiting suitable patients to participate in a trial; • delays by a collaboration partner in running a companion diagnostic on patient samples; • having patients complete a trial, including having patients enrolled in clinical trials dropping out of the trial prior to treatment, or return for post-treatment follow-up; • clinical trial sites deviating from trial protocol or dropping out of a trial; • addressing any patient safety concerns that arise during the course of a trial; • adding new clinical trial sites; or • manufacturing sufficient quantities of qualified materials under cGMPs, releasing product in accordance with specifications, and delivering product candidates for use in clinical trials.
In addition to the factors discussed in this “Risk Factors” section, these factors include: • the commencement, enrollment or results of our clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates; • our decision to initiate a clinical trial, not to initiate a clinical trial or to terminate an existing clinical trial; • adverse results or delays in clinical trials; • any delay in our regulatory filings for our product candidates and any adverse development or perceived adverse development with respect to the applicable regulatory authority’s review of such filings, including without limitation the FDA’s issuance of a “refusal to file” letter or a request for additional information; • our failure to commercialize our product candidates; • adverse regulatory decisions; • changes in laws or regulations applicable to our products, including but not limited to clinical trial requirements for approvals; • adverse developments concerning the manufacture or supply of our product candidates; • our inability to obtain adequate product supply for any approved product or inability to do so at acceptable prices; • our inability to establish collaborations if needed; • additions or departures of key scientific or management personnel; • unanticipated serious safety concerns related to immuno-oncology or related to the use of our product candidates or pre-conditioning regimen; • introduction of new products or services offered by us or our competitors; • changes in the status of one or more of our license or collaboration agreements, including any material disputes, amendments or terminations; • announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors; • our ability to effectively manage our growth; • the size and growth of our initial cancer or autoimmune diseases target markets; • our ability to successfully treat additional types of cancers or at different stages, or to treat autoimmune diseases; • actual or anticipated variations in quarterly operating results; • our cash position; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • publication of research reports about us or our industry, or immunotherapy in particular, or positive or negative recommendations or withdrawal of research coverage by securities analysts; • changes in the market valuations of similar companies; • overall performance of the equity markets; • sales of our common stock by us or our stockholders in the future; • trading volume of our common stock; • changes in accounting practices; • ineffectiveness of our disclosure controls or internal controls; • disagreements with our auditor or termination of an auditor engagement; • disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; • changes in the structure of healthcare payment systems; • significant lawsuits, including patent or stockholder litigation; • significant business disruptions caused by health epidemics or pandemics, or natural or man-made disasters; 80 Table of Contents • general political and economic conditions; and • other events or factors, many of which are beyond our control.
In addition to the factors discussed in this “Risk Factors” section, these factors include: • the commencement, enrollment or results of our clinical trials of our product candidates or any future clinical trials we may conduct, or changes in the development status of our product candidates; • our decision to initiate a clinical trial, not to initiate a clinical trial or to terminate an existing clinical trial; • adverse results or delays in clinical trials; • any delay in our regulatory filings for our product candidates and any adverse development or perceived adverse development with respect to the applicable regulatory authority’s review of such filings, including without limitation the FDA’s issuance of a “refusal to file” letter or a request for additional information; • our failure to commercialize our product candidates; • adverse regulatory decisions; • changes in laws or regulations applicable to our products, including but not limited to clinical trial requirements for approvals; • adverse developments concerning the manufacture or supply of our product candidates; • our inability to obtain adequate product supply for any approved product or inability to do so at acceptable prices; • our inability to establish collaborations if needed; • additions or departures of key scientific or management personnel; • unanticipated serious safety concerns related to immuno-oncology or related to the use of our product candidates or pre-conditioning regimen; • introduction of new products or services offered by us or our competitors; • changes in the status of one or more of our license or collaboration agreements, including any material disputes, amendments or terminations; • announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us or our competitors; • our ability to effectively manage our growth; 83 Table of Contents • the size and growth of our initial cancer or autoimmune diseases target markets; • our ability to successfully treat additional types of cancers or at different stages, or to treat autoimmune diseases; • actual or anticipated variations in quarterly operating results; • our cash position; • our failure to meet the estimates and projections of the investment community or that we may otherwise provide to the public; • publication of research reports about us or our industry, or immunotherapy in particular, or positive or negative recommendations or withdrawal of research coverage by securities analysts; • changes in the market valuations of similar companies; • overall performance of the equity markets; • sales of our common stock by us or our stockholders in the future; • trading volume of our common stock; • changes in accounting practices; • ineffectiveness of our disclosure controls or internal controls; • disagreements with our auditor or termination of an auditor engagement; • disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; • changes in the structure of healthcare payment systems; • significant lawsuits, including patent or stockholder litigation; • significant business disruptions caused by health epidemics or pandemics, or natural or man-made disasters; • general political and economic conditions; and • other events or factors, many of which are beyond our control.
The suppliers may be ill-equipped to support our needs, including generating data required for a BLA and in non-routine circumstances like an FDA or other comparable foreign regulatory authorities inspection or medical crisis, such as widespread contamination. We also face competition for supplies from other cell therapy companies.
The suppliers may be ill-equipped to support our needs, including generating data required for a BLA or an MAA and in non-routine circumstances like an FDA or other comparable foreign regulatory authorities inspection or medical crisis, such as widespread contamination. We also face competition for supplies from other cell therapy companies.
In addition, a new manufacturer would have to be educated in, or develop substantially equivalent processes for, production of our products after receipt of FDA or other comparable foreign regulatory authorities questions, if any. 64 Table of Contents • Our third-party manufacturers might be unable to timely formulate and manufacture our product or core reagents or produce the quantity and quality required to meet our clinical and commercial needs, if any. • Contract manufacturers may not be able to execute our manufacturing procedures appropriately. • Contract manufacturers may be subject to adverse legislative actions. • Manufacturers are subject to ongoing periodic unannounced inspection by the FDA, the Drug Enforcement Administration and corresponding state agencies or other comparable foreign regulatory authorities to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards.
In addition, a new manufacturer would have to be educated in, or develop substantially equivalent processes for, production of our products after receipt of FDA or other comparable foreign regulatory authorities questions, if any. • Our third-party manufacturers might be unable to timely formulate and manufacture our product or core reagents or produce the quantity and quality required to meet our clinical and commercial needs, if any. • Contract manufacturers may not be able to execute our manufacturing procedures appropriately. • Contract manufacturers may be subject to adverse legislative actions. 67 Table of Contents • Manufacturers are subject to ongoing periodic unannounced inspection by the FDA, the Drug Enforcement Administration and corresponding state agencies or other comparable foreign regulatory authorities to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards.
In addition, even if we believe the results are sufficiently compelling, such as for the ALPHA3 trial, the FDA, EMA, or comparable foreign regulatory authorities could ultimately require longer-term follow-up results, additional data from our clinical trials or additional trials that could delay or prevent our first BLA submission.
In addition, even if we believe the results are sufficiently compelling, such as for the ALPHA3 trial, the FDA, EMA, or comparable foreign regulatory authorities could ultimately require longer-term follow-up results, additional data from our clinical trials or additional trials that could delay or prevent our first BLA or MAA submission.
The occurrence of any of these business disruptions could seriously harm our operations and financial condition and increase our costs and expenses. Our ability to manufacture our product candidates could be disrupted if our operations or those of our suppliers are affected by a man-made or natural disaster or other business interruption.
The occurrence of any of these business disruptions could seriously harm our operations and financial condition and increase our costs and expenses. Our ability to manufacture or distribute our product candidates could be disrupted if our operations or those of our suppliers are affected by a man-made or natural disaster or other business interruption.
If there is no lawful manner for us to transfer personal data from the EEA, UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we may face significant adverse consequences, including the interruption or degradation of our operations (such as by limiting our ability to conduct clinical trial activities in Europe and elsewhere), the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, the inability to transfer data and work with partners, vendors and other third parties, increased exposure to regulatory actions, substantial fines, and injunctions against processing personal data necessary to operate our business.
If there is no lawful manner for us to transfer personal data from the EEA, UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we may face significant adverse consequences, including the interruption or degradation of our operations (such as by limiting our ability to conduct clinical trial activities in Europe and elsewhere), the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, the inability to transfer data and work with partners, vendors and other third parties, increased exposure to regulatory actions, substantial fines and penalties, and injunctions against processing or transferring personal data necessary to operate our business.
Additionally, the standard of care for first-line treatment in LBCL is well-established, and physicians and patients may be reluctant to adopt CAR T therapy in this setting due to concerns over safety, efficacy, cost, or logistical challenges associated administration.
Additionally, the standard of care for first-line treatment in LBCL is well-established, and physicians and patients may be reluctant to adopt CAR T therapy in this setting due to concerns over safety, efficacy, cost, or logistical challenges associated with administration.
Furthermore, our employees and personnel may use generative artificial intelligence technologies to perform their work, and the disclosure and use of personal data in such technologies is subject to various privacy laws and other privacy obligations. Governments have passed and are likely to pass additional laws regulating generative AI.
Furthermore, our employees and personnel may use generative artificial intelligence (AI) technologies to perform their work, and the disclosure and use of personal data in such technologies is subject to various privacy laws and other privacy obligations. Governments have passed and are likely to pass additional laws and regulations regulating generative AI.
A critical aspect to manufacturing allogeneic T cell product candidates involves gene editing the healthy donor T cells in an effort to avoid GvHD and to limit the patient’s immune system from attacking the allogeneic T cells. GvHD results when allogeneic T cells start recognizing the patient’s normal tissue as foreign.
A critical aspect to manufacturing allogeneic CAR T cell product candidates involves gene editing the healthy donor T cells in an effort to avoid GvHD and to limit the patient’s immune system from attacking the allogeneic T cells. GvHD results when allogeneic T cells start recognizing the patient’s normal tissue as foreign.
We operate CF1, a manufacturing facility located in Newark, California, that is designed to support our clinical trials and potential commercial production and worldwide distribution of allogeneic CAR T cell products for blood cancers, solid tumors and autoimmune diseases.
We operate CF1, our manufacturing facility located in Newark, California, that is designed to support our clinical trials and potential commercial production and worldwide distribution of allogeneic CAR T cell products for blood cancers, solid tumors and autoimmune diseases.
Some of these provisions include: • a board of directors divided into three classes serving staggered three-year terms, such that not all members of the board will be elected at one time; • a prohibition on stockholder action through written consent, which requires that all stockholder actions be taken at a meeting of our stockholders; • a requirement that special meetings of stockholders be called only by the chair of the board of directors, the chief executive officer, or by a majority of the total number of authorized directors; • advance notice requirements for stockholder proposals and nominations for election to our board of directors; • a requirement that no member of our board of directors may be removed from office by our stockholders except for cause and, in addition to any other vote required by law, upon the approval of not less than two-thirds of all outstanding shares of our voting stock then entitled to vote in the election of directors; • a requirement of approval of not less than two-thirds of all outstanding shares of our voting stock to amend any bylaws by stockholder action or to amend specific provisions of our certificate of incorporation; and • the authority of the board of directors to issue preferred stock on terms determined by the board of directors without stockholder approval and which preferred stock may include rights superior to the rights of the holders of common stock.
Some of these provisions include: • a board of directors divided into three classes serving staggered three-year terms, such that not all members of the board will be elected at one time; • a prohibition on stockholder action through written consent, which requires that all stockholder actions be taken at a meeting of our stockholders; 85 Table of Contents • a requirement that special meetings of stockholders be called only by the chair of the board of directors, the chief executive officer, or by a majority of the total number of authorized directors; • advance notice requirements for stockholder proposals and nominations for election to our board of directors; • a requirement that no member of our board of directors may be removed from office by our stockholders except for cause and, in addition to any other vote required by law, upon the approval of not less than two-thirds of all outstanding shares of our voting stock then entitled to vote in the election of directors; • a requirement of approval of not less than two-thirds of all outstanding shares of our voting stock to amend any bylaws by stockholder action or to amend specific provisions of our certificate of incorporation; and • the authority of the board of directors to issue preferred stock on terms determined by the board of directors without stockholder approval and which preferred stock may include rights superior to the rights of the holders of common stock.
Events that may prevent successful or timely completion of clinical development include: • inability to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation of clinical studies; • delays in sufficiently developing, characterizing, controlling or optimizing a manufacturing process suitable for clinical trials, including the validation and deployment of release assays; • difficulty sourcing healthy donor material of sufficient quality and in sufficient quantity to meet our development needs; • delays in developing, obtaining regulatory approval for, or implementing suitable assays for screening patients for eligibility for trials with respect to certain product candidates; • the number of patients who consent to be screened for the ALPHA3 trial may be lower than we expect given the current well-established medical practice of frontline therapy for LBCL and the history of slow patient recruitment in other frontline LBCL trials • the screen failure rate for clinical trials of our product candidates may be higher than we anticipate, requiring us to screen larger numbers of patients than originally planned.
Events that may prevent successful or timely completion of clinical development include: • inability to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation of clinical studies; 47 Table of Contents • delays in sufficiently developing, characterizing, controlling or optimizing a manufacturing process suitable for clinical trials, including the validation and deployment of release assays; • difficulty sourcing healthy donor material of sufficient quality and in sufficient quantity to meet our development needs; • delays in developing, obtaining regulatory approval for, or implementing suitable assays for screening patients for eligibility for trials with respect to certain product candidates; • the number of patients who consent to be screened for the ALPHA3 trial may be lower than we expect given the current well-established medical practice of frontline therapy for LBCL and the history of slow patient recruitment in other frontline LBCL trials • the screen failure rate for clinical trials of our product candidates may be higher than we anticipate, requiring us to screen larger numbers of patients than originally planned.
Because our allogeneic T cell product candidates are based on new technologies and will require the creation of inventory of mass-produced, off-the-shelf product, they will require extensive research and development and have substantial manufacturing and processing costs.
Because our allogeneic CAR T cell product candidates are based on new technologies and will require the creation of inventory of mass-produced, off-the-shelf product, they will require extensive research and development and have substantial manufacturing and processing costs.
We expect to incur significant expenditures for the foreseeable future, and we expect these expenditures to increase as we continue our research and development of, and seek regulatory approvals for, product candidates based on our engineered allogeneic T cell platform.
We expect to incur significant expenditures for the foreseeable future, and we expect these expenditures to increase as we continue our research and development of, and seek regulatory approvals for, product candidates based on our engineered allogeneic CAR T cell platform.
In addition, we are reliant on Foresight Diagnostics to perform MRD testing. A delay or failure by Foresight Diagnostics to perform MRD testing may negatively impact our ability to conduct ALPHA3 trial as planned, or prevent us from conducting ALPHA3 trial.
In addition, we are reliant on Foresight Diagnostics to perform MRD testing. A delay or failure by Foresight Diagnostics to perform MRD testing may negatively impact our ability to conduct the ALPHA3 trial as planned, or prevent us from conducting the ALPHA3 trial.
Because cema-cel, ALLO-316, ALLO-715 and ALLO-605, products designed for use in patients with cancer, and ALLO-329, designed for use in patients with autoimmune disease, are or will be among the first allogeneic products to be evaluated in the clinic, the failure of any such product candidates, or the failure of other allogeneic T cell therapies, including for reasons due to safety, efficacy or durability, may impede our ability to develop our product candidates, and significantly influence physicians’ and regulators’ opinions in regard to the viability of our entire pipeline of allogeneic T cell therapies.
Because cema-cel, ALLO-316, and ALLO-715, products designed for use in patients with cancer, and ALLO-329, designed for use in patients with autoimmune disease, are or will be among the first allogeneic products to be evaluated in the clinic, the failure of any such product candidates, or the failure of other allogeneic CAR T cell therapies, including for reasons due to safety, efficacy or durability, may impede our ability to develop our product candidates, and significantly influence physicians’ and regulators’ opinions in regard to the viability of our entire pipeline of allogeneic CAR T cell therapies.
In the future, Foresight Diagnostics may not be able to successfully and timely conduct the ALPHA3 MRD tests, obtain regulatory approval of CLARITY or successfully support commercialization of cema-cel, if approved.
In the future, Foresight Diagnostics and/or Natera may not be able to successfully and timely conduct the ALPHA3 MRD tests, obtain regulatory approval of CLARITY or successfully support commercialization of cema-cel, if approved.
For example, FDA may determine that results from our Phase 2 ALPHA3 trial are not sufficient to establish that cema-cel is safe and effective, and FDA may require additional trials.
For example, the FDA may determine that results from our Phase 2 ALPHA3 trial are not sufficient to establish that cema-cel is safe and effective, and the FDA may require additional trials.
Advancing these novel product candidates creates significant challenges for us, including: • manufacturing our product candidates to our or regulatory specifications and in a timely manner to support our clinical trials, and, if approved, commercialization; • sourcing clinical and, if approved, commercial supplies for the raw materials used to manufacture our product candidates; 59 Table of Contents • understanding and addressing variability in the quality of a donor’s T cells, which could ultimately affect our ability to produce product in a reliable and consistent manner and treat certain patients; • educating medical personnel regarding the potential side effect profile of our product candidates, if approved, such as the potential adverse side effects related to CRS, neurotoxicity, GvHD, IEC-HS, prolonged cytopenia, aplastic anemia and neutropenic sepsis; • using medicines to preempt or manage adverse side effects of our product candidates and such medicines may be difficult to source or costly or may not adequately control the side effects and/or may have other safety risks or a detrimental impact on the efficacy of the treatment; • conditioning patients with chemotherapy and ALLO-647 or other lymphodepletion agents in advance of administering our product candidates, which may be difficult to source, costly or increase the risk of infections and other adverse side effects; • obtaining regulatory approval, as the FDA and other comparable foreign regulatory authorities have limited experience with development of allogeneic T cell therapies for cancer or autoimmune diseases; and • establishing sales and marketing capabilities upon obtaining any regulatory approval to gain market acceptance of a novel therapy.
Advancing these novel product candidates creates significant challenges for us, including: • manufacturing our product candidates to our or regulatory specifications and in a timely manner to support our clinical trials, and, if approved, commercialization; • sourcing clinical and, if approved, commercial supplies for the raw materials used to manufacture our product candidates; • understanding and addressing variability in the quality of a donor’s T cells, which could ultimately affect our ability to produce product in a reliable and consistent manner and treat certain patients; • educating medical personnel regarding the potential side effect profile of our product candidates, if approved, such as the potential adverse side effects related to CRS, neurotoxicity, GvHD, IEC-HS, prolonged cytopenia, aplastic anemia and neutropenic sepsis; • using medicines to preempt or manage adverse side effects of our product candidates and such medicines may be difficult to source or costly or may not adequately control the side effects and/or may have other safety risks or a detrimental impact on the efficacy of the treatment; • conditioning patients with chemotherapy or other lymphodepletion agents in advance of administering our product candidates, which may be difficult to source, costly or increase the risk of infections and other adverse side effects; • obtaining regulatory approval, as the FDA and other comparable foreign regulatory authorities have limited experience with development of allogeneic T cell therapies for cancer or autoimmune diseases; and • establishing sales and marketing capabilities upon obtaining any regulatory approval to gain market acceptance of a novel therapy.
We have limited experience in managing the allogeneic T cell engineering process, and our allogeneic processes may be more difficult or more expensive than the approaches taken by our competitors.
We have limited experience in managing the allogeneic CAR T cell engineering process, and our allogeneic processes may be more difficult or more expensive than the approaches taken by our competitors.
We have concentrated our research, development and manufacturing efforts on our engineered allogeneic T cell therapy and our future success depends on the successful development of this therapeutic approach.
We have concentrated our research, development and manufacturing efforts on our engineered allogeneic CAR T cell therapy and our future success depends on the successful development of this therapeutic approach.
In certain foreign jurisdictions, such as European Union (EU), we anticipate that the CLARITY assay will be regulated as an in vitro diagnostic medical device.
In certain foreign jurisdictions, such as the European Union (EU), we anticipate that the CLARITY TM assay will be regulated as an in vitro diagnostic medical device.
Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and lawsuits. Obligations related to data privacy and security (including consumers’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty. Additionally, these obligations may be subject to differing applications and interpretations, which may be inconsistent or conflict among jurisdictions.
Our use of this technology could result in additional compliance costs, regulatory investigations and actions, and lawsuits. Obligations related to data privacy and security (including individuals’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty. Additionally, these obligations may be subject to differing applications and interpretations, which may be inconsistent or conflict among jurisdictions.
If we or the third parties with whom we work fail, or are perceived to have failed, to address or comply with applicable obligations related to data privacy and security, we could face significant consequences including, but not limited to, government enforcement actions (e.g., investigations, fines, penalties, audits and inspections, and similar); litigation (including class-related claims) and mass arbitration demands; additional 58 Table of Contents reporting requirements and/or oversight; temporary or permanent bans or restrictions on all or some processing of personal data; orders to destroy or not use personal data; and imprisonment of company officials.
If we or the third parties with whom we work fail, or are perceived to have failed, to address or comply with applicable obligations related to data privacy and security, we could face significant consequences including, but not limited to, government enforcement actions (e.g., investigations, fines, penalties, audits and inspections, and similar); litigation (including class-related claims) and mass arbitration demands; additional reporting requirements and/or oversight; temporary or permanent bans or restrictions on all or some processing of personal data; orders to destroy or not use personal data; and imprisonment of company officials.
Although the Foresight CLARITY ™ Investigational Use Only (IUO) MRD test, powered by PhasED-Seq, has received IDE approval from the FDA allowing PhasEd-Seq to be used as part of the ALPHA3 trial, there can be no assurance that Foresight Diagnostic will be able to obtain the necessary regulatory approvals to support ALPHA3 clinical trial sites outside the US, or that we would be able to manage logistical challenges associated with timely international shipment of patient samples to Foresight’s US facility for testing, all of which could delay the expansion of our ALPHA3 trial to trial sites outside the US.
Although the Foresight CLARITY™ Investigational Use Only (IUO) MRD test, powered by PhasED-Seq, has received IDE approval from the FDA allowing PhasEd-Seq to be used as part of the ALPHA3 trial, there can be no assurance that Foresight Diagnostic will be able to obtain the necessary regulatory approvals to support ALPHA3 clinical trial sites outside the U.S., or that we would be able to manage logistical challenges associated with timely international shipment of patient samples to Foresight’s U.S. facility for testing, all of which could delay the expansion of our ALPHA3 trial to trial sites outside the U.S.
For instance, our agreements with Cellectis, Servier, Notch, Antion, and Foresight Diagnostics require significant research and development that may not result in the development and commercialization of product candidates. We cannot be certain that, following a strategic transaction or license, we will achieve the results, revenue or specific net income that justifies such transaction.
For instance, our agreements with Cellectis, Servier, Roche (formerly, Notch), Antion, and Foresight Diagnostics require significant research and development that may not result in the development and commercialization of product candidates. We cannot be certain that, following a strategic transaction or license, we will achieve the results, revenue or specific net income that justifies such transaction.
We and the third parties with whom we work are subject to a variety of evolving threats, including but not limited to social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service credential stuffing attacks, credential harvesting, adware, ransomware, supply chain attacks, personnel misconduct or error, attacks 54 Table of Contents enhanced or facilitated by AI, and other similar threats.
We and the third parties with whom we work are subject to a variety of evolving threats, including but not limited to social-engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing attacks, credential harvesting, adware, ransomware attacks, supply-chain attacks, personnel misconduct or error, attacks enhanced or facilitated by AI, and other similar threats.
For example, in November 2024, one of our vendors notified us that they had detected suspicious activity on their network that compromised several email accounts the vendor used to communicate with us. We took appropriate remedial measures, and based on our investigation, we concluded that the incident did not compromise our systems.
For example, in November 2024, one of our vendors notified us that they had detected suspicious activity on their network that compromised several email accounts the vendor used to communicate with us. We took appropriate remedial measures, and based on our investigation, we concluded that the incident did not result in a compromise our systems.
For example, the number of patients who have MRD at the end of front-line treatment in ALPHA3 may be lower than we expect, requiring more patients to be screened; • delays in reaching a consensus with regulatory agencies on study design; • delays in reaching agreement on acceptable terms with prospective CROs and clinical study sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical study sites; • delays in obtaining required IRB approval or approval of other ancillary regulatory committees at each clinical study site; 46 Table of Contents • imposition of a temporary or permanent clinical hold by regulatory agencies for a number of reasons, including after review of an IND application or amendment, or equivalent application or amendment; as a result of a new safety finding that presents uncertain or unreasonable risk to clinical trial participants; a negative finding from an inspection of our or our collaborator’s clinical study operations or our study sites; developments on trials conducted by competitors for related technology that raises FDA or other comparable foreign regulatory authority concerns about risk to patients of the technology broadly; or if the FDA or other comparable foreign regulatory authorities find that the investigational protocol or plan is clearly deficient to meet its stated objectives; • delays in recruiting suitable patients to participate in our clinical studies; • difficulty collaborating with patient groups and investigators; • failure by our CROs, other third parties or us to adhere to clinical study requirements; • failure to perform in accordance with the FDA’s good clinical practices (GCP) requirements or equivalent regulatory guidelines in other countries; • delays or failures in the transfer of manufacturing processes to any CDMO or our own manufacturing facility or any other development or commercialization partner for the manufacture of product candidates; • delays in having patients complete participation in a study or return for post-treatment follow-up; • patients dropping out of a study; • occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits; • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; • changes in the standard of care on which a clinical development plan was based, which may require new or additional trials; • the cost of clinical studies of our product candidates being greater than we anticipate; • clinical studies of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical studies or abandon product development programs; • delays or failure to secure supply agreements with suitable raw material suppliers, or any failures by suppliers to meet our quantity or quality requirements for necessary raw materials; • shortage, interruption, or failure to secure commercially available and/or investigational drug products that are required to conduct clinical trials with our allogeneic CAR T product candidates; and • delays in manufacturing, testing, releasing, validating, or importing/exporting sufficient stable quantities of our product candidates for use in clinical studies or the inability to do any of the foregoing.
For example, the number of patients who have MRD at the end of front-line treatment in ALPHA3 may be lower than we expect requiring more patients to be screened; • delays in reaching a consensus with regulatory agencies on study design; • delays in reaching agreement on acceptable terms with prospective CROs and clinical study sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical study sites; • delays in obtaining required IRB approval or approval of other ancillary regulatory committees at each clinical study site; • imposition of a temporary or permanent clinical hold by regulatory agencies for a number of reasons, including after review of an IND application or amendment, or equivalent application or amendment; as a result of a new safety finding that presents uncertain or unreasonable risk to clinical trial participants; a negative finding from an inspection of our or our collaborator’s clinical study operations or our study sites; developments on trials conducted by competitors for related technology that raises FDA or other comparable foreign regulatory authority concerns about risk to patients of the technology broadly; or if the FDA or other comparable foreign regulatory authorities find that the investigational protocol or plan is clearly deficient to meet its stated objectives; • delays in recruiting suitable patients to participate in our clinical studies; • delays in activating clinical trial sites; • delays in obtaining the necessary regulatory approvals to expand clinical trials to countries outside the United States, including approvals relating to any required companion diagnostic; • difficulty collaborating with patient groups and investigators; • failure by our CROs, other third parties or us to adhere to clinical study requirements; • failure to perform in accordance with the FDA’s good clinical practices (GCP) requirements or equivalent regulatory guidelines in other countries; • delays or failures in the transfer of manufacturing processes to any CDMO or our own manufacturing facility or any other development or commercialization partner for the manufacture of product candidates; • delays in having patients complete participation in a study or return for post-treatment follow-up; • patients dropping out of a study; • occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits; • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; • changes in the standard of care on which a clinical development plan was based, which may require new or additional trials; • the cost of clinical studies of our product candidates being greater than we anticipate; 48 Table of Contents • clinical studies of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical studies or abandon product development programs; • delays or failure to secure supply agreements with suitable raw material suppliers, or any failures by suppliers to meet our quantity or quality requirements for necessary raw materials; • shortage, interruption, or failure to secure commercially available and/or investigational drug products that are required to conduct clinical trials with our allogeneic CAR T product candidates; and • delays in manufacturing, testing, releasing, validating, or importing/exporting sufficient stable quantities of our product candidates for use in clinical studies or the inability to do any of the foregoing.
The success of our strategic transactions, including our acquisition of CAR T cell assets from Pfizer, licenses with Cellectis, Servier, Notch, Antion, our strategic collaboration with Foresight Diagnostics, and our joint venture with HBP and any future strategic transactions depends on the risks and uncertainties involved including: 53 Table of Contents • technical difficulties associated with advancing partnered programs; • unanticipated liabilities related to acquired companies or joint ventures; • difficulties integrating acquired personnel, technologies and operations into our existing business; • retention of key employees; • managerial challenges associated with the oversight of partnered programs; • disagreements regarding each party’s contractual rights and obligations under our partnership agreements; • costs and uncertainties related to managing disputes with any strategic partners; • increases in our expenses and reductions in our cash available for operations and other uses; • inability of our strategic partners to access suitable capital; • disruption in or termination of our relationships with collaborators or suppliers as a result of such a transaction; and • possible write-offs or impairment charges relating to acquired businesses or joint ventures.
The success of our strategic transactions, including our acquisition of CAR T cell assets from Pfizer, licenses with Cellectis, Servier, Roche (formerly, Notch), Antion, our strategic collaboration with Foresight Diagnostics, and our joint venture with HBP and any future strategic transactions depends on the risks and uncertainties involved including: • technical difficulties associated with advancing partnered programs; • unanticipated liabilities related to acquired companies or joint ventures; • difficulties integrating acquired personnel, technologies and operations into our existing business; • retention of key employees; • managerial challenges associated with the oversight of partnered programs; • disagreements regarding each party’s contractual rights and obligations under our partnership agreements; • costs and uncertainties related to managing disputes with any strategic partners; • increases in our expenses and reductions in our cash available for operations and other uses; • inability of our strategic partners to access suitable capital; • disruption in or termination of our relationships with collaborators or suppliers as a result of such a transaction; and • possible write-offs or impairment charges relating to acquired businesses or joint ventures.
Our contract manufacturers would also be subject to the same risks we face in developing our own manufacturing capabilities, as described above. Our current and potential future CDMOs may also be required to shut down in response to health epidemics or pandemics, or they may prioritize manufacturing for therapies or vaccines for other diseases.
Our contract manufacturers would also be subject to the same risks we face in developing our own manufacturing capabilities, as described above. Our potential future CDMOs may also be required to shut down in response to health epidemics or pandemics, or they may prioritize manufacturing for therapies or vaccines for other diseases.
Further, a clinical trial may be suspended or terminated by us, the Institutional Review Boards (IRBs) or Ethics Committees for the institutions in which such trials are being conducted or by the FDA or other comparable foreign regulatory authorities due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other comparable foreign regulatory authorities resulting in the imposition of a clinical hold, safety issues or adverse side effects, failure to demonstrate a benefit from using a product candidate, changes in governmental regulations or administrative actions, lack of adequate funding to continue the clinical trial, or based on a recommendation by any Data Safety Monitoring Committee.
Further, a clinical trial may be suspended or terminated by us, the Institutional Review Boards (IRBs) or Ethics Committees for the institutions in which such trials are being conducted or by the FDA or other comparable foreign regulatory authorities due to a number of factors, including failure to 70 Table of Contents conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or other comparable foreign regulatory authorities resulting in the imposition of a clinical hold, safety issues or adverse side effects, failure to demonstrate a benefit from using a product candidate, changes in governmental regulations or administrative actions, lack of adequate funding to continue the clinical trial, or based on a recommendation by any data safety monitoring board or committee.
Future undesirable or unacceptable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory 42 Table of Contents approval by the FDA or other comparable foreign regulatory authorities.
Future undesirable or unacceptable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in a more restrictive label or the delay or denial of regulatory 43 Table of Contents approval by the FDA or other comparable foreign regulatory authorities.
For additional information regarding our competition, see the section entitled “Business—Competition” included in this Annual Report. We are highly dependent on our key personnel, and if we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy.
For additional information regarding our competition, refer to the section entitled “Business—Competition” included in this Annual Report. We are highly dependent on our key personnel, and if we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy.
Similarly, if any third-party patent were held by a court of competent jurisdiction to cover aspects of our formulations, processes for manufacture or methods of 76 Table of Contents use, including combination therapy or patient selection methods, the holders of any such patent may be able to block our ability to develop and commercialize the product candidate unless we obtained a license or until such patent expires or is finally determined to be held not infringed, unpatentable, invalid or unenforceable.
Similarly, if any third-party patent were held by a court of competent jurisdiction to cover aspects of our formulations, processes for manufacture or methods of use, including combination therapy or patient selection methods, the holders of any such patent may be able to block our ability to develop and commercialize the product candidate unless we obtained a license or until such patent expires or is finally determined to be held not infringed, unpatentable, invalid or unenforceable.
If these third parties do not successfully carry out 63 Table of Contents their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to complete development of, obtain regulatory approval of or successfully commercialize our product candidates.
If these third parties do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to complete development of, obtain regulatory approval of or successfully commercialize our product candidates.
Accordingly, we expect that we will be subject to additional risks related to operating in foreign countries, including: • differing regulatory requirements in foreign countries; • unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements, including recently imposed tariffs which may impact certain of our key raw materials that we import, and which could impact our cost of goods for our product candidates; • differing standards and privacy requirements for the conduct of clinical trials; • geographic variations in genetics, comorbidities, environmental factors, treatment patterns, and healthcare practices may impact the safety profile or efficacy of our product candidates; • increased difficulties in managing the logistics and transportation of storing and shipping product candidates produced in the United States, shipping the product candidate to the patient abroad, and shipping patient samples to the United States for screening tests; • import and export requirements and restrictions; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign taxes, including withholding of payroll taxes; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; • difficulties staffing and managing foreign operations; • workforce uncertainty in countries where labor unrest is more common than in the United States; • differing payor reimbursement regimes, governmental payors or patient self-pay systems, and price controls; • potential liability under the Foreign Corrupt Practices Act of 1977 or comparable foreign regulations; • challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; • challenges with obtaining any local supply of drugs or agents used with our product candidates, which are required by certain local clinical trial sites before conducting any study; and • business interruptions resulting from future health epidemics or pandemics, or natural or man-made disasters, including earthquakes, tsunamis, fires or other medical epidemics, or geo-political actions, including war and terrorism.
Accordingly, we expect that we will be subject to additional risks related to operating in foreign countries, including: • differing regulatory requirements in foreign countries; • unexpected changes in tariffs, trade barriers, price and exchange controls and other regulatory requirements, including recently imposed tariffs which may impact certain of our key raw materials that we import, and which could impact our cost of goods for our product candidates; • differing standards and privacy requirements for the conduct of clinical trials; • jurisdiction-specific regulatory, reimbursement, and clinical adoption dynamics for diagnostic assays used for patient identification and selection; • geographic variations in genetics, comorbidities, environmental factors, treatment patterns, and healthcare practices may impact the safety profile or efficacy of our product candidates; • increased difficulties in managing the logistics and transportation of storing and shipping product candidates produced in the United States, shipping the product candidate to the patient abroad, and shipping patient samples to the United States for screening tests; • import and export requirements and restrictions; • economic weakness, including inflation, or political instability in particular foreign economies and markets; • compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; • foreign taxes, including withholding of payroll taxes; • foreign currency fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to doing business in another country; • difficulties staffing and managing foreign operations; • workforce uncertainty in countries where labor unrest is more common than in the United States; • differing payor reimbursement regimes, governmental payors or patient self-pay systems, and price controls; • potential liability under the Foreign Corrupt Practices Act of 1977 or comparable foreign regulations; • challenges enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad; 53 Table of Contents • challenges with obtaining any local supply of drugs or agents used with our product candidates, which are required by certain local clinical trial sites before conducting any study; and • business interruptions resulting from future health epidemics or pandemics, or natural or man-made disasters, including earthquakes, tsunamis, fires or other medical epidemics, or geo-political actions, including war and terrorism.
These consequences may include: government enforcement actions (for example, investigations, fines, penalties, audits, and inspections); additional reporting requirements and/or oversight; restrictions on processing sensitive information (including personal data); litigation (including class claims) and mass arbitration; indemnification obligations; negative publicity; reputational harm; monetary fund diversions; interruptions in our operations (including availability of data); financial loss; and other similar harms.
These consequences may include: government enforcement actions (for example, investigations, fines, penalties, audits, and inspections); additional reporting requirements and/or oversight; restrictions on processing sensitive information (including personal data); litigation (including class claims) and mass arbitration; indemnification obligations; negative publicity; reputational harm; monetary fund diversions; diversion of management attention; interruptions in our operations (including availability of data); financial loss; and other similar harms.
Furthermore, the FDA can waive orphan exclusivity if we are unable to manufacture sufficient supply of our product or if a subsequent applicant demonstrates clinical superiority over our product. The FDA granted orphan drug designation to ALLO-605 and ALLO-715 for the treatment of multiple myeloma.
Furthermore, the FDA can waive orphan exclusivity if we are unable to manufacture sufficient supply of our product or if a subsequent applicant demonstrates clinical superiority over our product. The FDA granted orphan drug designation to ALLO-715 for the treatment of multiple myeloma.
Even if our trials begin as planned, issues may arise that could suspend or terminate such clinical trials. A failure of one or more clinical studies can occur at any stage of testing, and our future clinical studies may not be successful.
Even if our trials begin as planned, issues may arise that could suspend or terminate such clinical trials or a portion thereof. A failure of one or more clinical studies can occur at any stage of testing, and our future clinical studies may not be successful.
Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States when there is no reasonable expectation that the cost of developing and making available the drug or biologic in the United States will be recovered from sales in the United States for that drug or biologic.
Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, defined as a disease or condition with a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States when there is no reasonable expectation that the cost of developing 73 Table of Contents and making available the drug or biologic in the United States will be recovered from sales in the United States for that drug or biologic.
The MRD assay represents a novel approach to detecting the presence of minimal disease and the design of our trial is based on certain assumptions regarding the performance of the MRD assay, including assumptions regarding the anticipated MRD+ rate being consistent with published data.
The CLARITY TM MRD assay represents a novel approach to detecting the presence of minimal disease and the design of our trial is based on certain assumptions regarding the performance of the MRD assay, including assumptions regarding the anticipated MRD+ rate being consistent with published data.
If we are unable to successfully develop, obtain approval for, and commercialize our CAR T therapy in this novel setting, our business, financial condition, and results of operations could be adversely affected. 44 Table of Contents The time required for regulatory approval of the CLARITY assay in jurisdictions outside the U.S. may be protracted, which presents regulatory, operational, and commercialization risks.
If we are unable to successfully develop, obtain approval for, and commercialize our CAR T therapy in this novel setting, our business, financial condition, and results of operations could be adversely affected. The time required for regulatory approval of the CLARITY assay in jurisdictions outside the U.S. may be protracted, which presents regulatory, operational, and commercialization risks.
If they experience delays, fail to meet regulatory requirements, or prioritize other programs over the CLARITY assay, our clinical development efforts outside the US could be significantly delayed. We may have limited visibility into the approval timeline and decision-making process, which could hinder our ability to accurately forecast any trial initiation and enrollment.
If they experience delays, fail to meet regulatory requirements, or prioritize other programs over the CLARITY assay, our clinical development efforts outside the U.S. could be significantly delayed. We may have limited visibility into the approval timeline and decision-making process, which could hinder our ability to accurately forecast any trial initiation and enrollment.
Moreover, our reliance on these third parties reduces our control over manufacturing and quality assurance processes. Any performance failure or compliance breach by our named vendors—such as failing to meet regulatory standards or 61 Table of Contents encountering financial or operational difficulties—could adversely affect the ongoing development and potential commercialization of our product candidates.
Moreover, our reliance on these third parties reduces our control over manufacturing and quality assurance processes. Any performance failure or compliance breach by our named vendors—such as failing to meet regulatory standards or encountering financial or operational difficulties—could adversely affect the ongoing development and potential commercialization of our product candidates.
If we, or our collaborators, are required by the FDA, or comparable foreign regulatory authorities, to obtain approval (or clearance, or certification) of a companion diagnostic device in connection with approval of one of our product candidates, and we, or our collaborators, do not obtain, or face delays in obtaining, approval (or clearance, or certification) of a companion diagnostic device, we will not be able to commercialize the product candidate, and our ability to generate revenue will be materially impaired.
If we, or our collaborators, are required by the FDA, or comparable foreign regulatory authorities, to obtain approval (or clearance, or certification) of a companion diagnostic device in connection with approval of one of our product candidates, and we, or our collaborators, do not obtain, or face delays in obtaining, approval (or clearance, or certification) of a 72 Table of Contents companion diagnostic device, we will not be able to commercialize the product candidate, and our ability to generate revenue will be materially impaired.
As a result, there is a risk that 48 Table of Contents Foresight Diagnostics might work with our competitors to enable a competing clinical trial involving the same MRD positive patient population that we plan to enroll in ALPHA3, which would reduce the number of patients who are available to participate in ALPHA3, and potentially delay completion of ALPHA3.
As a result, there is a risk that Foresight Diagnostics might work with our competitors to enable a competing clinical trial involving the same MRD positive patient population that we plan to enroll in ALPHA3, which would reduce the number of patients who are available to participate in ALPHA3, and potentially delay completion of ALPHA3.
We or our independent registered public accounting firm may not be able to conclude on an ongoing basis that we have effective internal control over 81 Table of Contents financial reporting, which could harm our operating results, cause investors to lose confidence in our reported financial information and cause the trading price of our stock to fall.
We or our independent registered public accounting firm may not be able to conclude on an ongoing basis that we have effective internal control over financial reporting, which could harm our operating results, cause investors to lose confidence in our reported financial information and cause the trading price of our stock to fall.
Moreover, we may not be successful in our efforts to establish a strategic partnership or other alternative arrangements for our product candidates because they may be deemed to be at too early of a stage of development for collaborative effort and third parties may not view our product candidates as having the requisite potential to demonstrate safety and efficacy.
Moreover, we may not be successful in our efforts to establish a strategic partnership or other alternative arrangements for our product 55 Table of Contents candidates because they may be deemed to be at too early of a stage of development for collaborative effort and third parties may not view our product candidates as having the requisite potential to demonstrate safety and efficacy.
In addition to the protection afforded by patents, we seek to rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable, processes for which patents are difficult to enforce and any 75 Table of Contents other elements of our product discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents.
In addition to the protection afforded by patents, we seek to rely on trade secret protection and confidentiality agreements to protect proprietary know-how that is not patentable, processes for which patents are difficult to enforce and any other elements of our product discovery and development processes that involve proprietary know-how, information or technology that is not covered by patents.
We are in the early stages of developing our platform and we have experienced significant development challenges, such as with the prior clinical hold by the FDA, and there can be no assurance that any development problems we have now or experience in the future will not cause 40 Table of Contents significant delays or unanticipated costs, or that such development problems can be overcome.
We are in the early stages of developing our platform and we have experienced significant development challenges, such as with the prior clinical hold by the FDA, and there can be no assurance that any development problems we have now or experience in the future will not cause significant delays or unanticipated costs, or that such development problems can be overcome.
If we are unable or decide not to establish internal sales, marketing and distribution capabilities, we will pursue collaborative arrangements regarding the sales and marketing of our products; however, there can be no assurance that we will 50 Table of Contents be able to establish or maintain such collaborative arrangements, or if we are able to do so, that they will have effective sales forces or be on favorable terms.
If we are unable or decide not to establish internal sales, marketing and distribution capabilities, we will pursue collaborative arrangements regarding the sales and marketing of our products; however, there can be no assurance that we will be able to establish or maintain such collaborative arrangements, or if we are able to do so, that they will have effective sales forces or be on favorable terms.
Even if we are successful in defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees. Risks Related to Ownership of Our Common Stock 79 Table of Contents The price of our stock has been and may continue to be volatile, and you could lose all or part of your investment.
Even if we are successful in defending against these claims, litigation could result in substantial cost and be a distraction to our management and employees. Risks Related to Ownership of Our Common Stock The price of our stock has been and may continue to be volatile, and you could lose all or part of your investment.
Introducing any product manufactured at our manufacturing facility into an ongoing clinical trial would be subject to FDA review, and may result in increased costs and delays in conducting such trial, submitting a biologics license application (BLA) and/or gaining FDA or other comparable foreign regulatory authority approval.
Introducing any product manufactured at our manufacturing facility into an ongoing clinical trial would be subject to FDA review, and may result in increased costs and delays in conducting such trial, submitting a biologics license application (BLA) or marketing authorization application (MAA) and/or gaining FDA or other comparable foreign regulatory authority approval.
Regenerative Medicine Advanced Therapy designation and fast track designation may not lead to a faster development or regulatory review or approval process and it does not increase the likelihood that our product candidates will receive marketing approval. We have received Regenerative Medicine Advanced Therapy (RMAT) designation for cema-cel, ALLO-316, and ALLO-715 and fast track designation for ALLO-605, ALLO-316, and ALLO-647.
Regenerative Medicine Advanced Therapy designation and fast track designation may not lead to a faster development or regulatory review or approval process and it does not increase the likelihood that our product candidates will receive marketing approval. We have received Regenerative Medicine Advanced Therapy (RMAT) designation for cema-cel, ALLO-316, and ALLO-715 and fast track designation for ALLO-316 and ALLO-329.
In addition, our product candidates could be delayed in receiving approval or fail to receive regulatory approval for many reasons, including the following: • the inability to resolve any future clinical hold; • the FDA, EMA, or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials; • we may be unable to demonstrate to the satisfaction of the FDA, EMA, or comparable foreign regulatory authorities that our product candidates are safe and effective for any of their proposed indications; • the results of clinical trials may not meet the level of statistical significance required by the FDA, EMA, or comparable foreign regulatory authorities for approval, including due to the heterogeneity of patient populations; • we may be unable to demonstrate that our product candidates’ clinical and other benefits outweigh their safety risks; • the FDA, EMA, or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our product candidates may not be sufficient to the satisfaction of the FDA, EMA, or comparable foreign regulatory authorities to support the submission of a BLA or other comparable submission in foreign jurisdictions or to obtain regulatory approval in the United States or elsewhere; • the FDA, EMA, or comparable foreign regulatory authorities will review extensive CMC data, our manufacturing process and inspect the relevant commercial manufacturing facility and may not approve our manufacturing process or facility; • the approval policies or regulations of the FDA, EU, or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval; and • we may be unable to agree on any required pediatric investigation plan with regulatory authorities prior to any BLA filing.
In addition, our product candidates could be delayed in receiving approval or fail to receive regulatory approval for many reasons, including the following: • the inability to resolve any future clinical hold; • the FDA, EMA, or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials or any changes thereto submitted in protocol amendments; • we may be unable to demonstrate to the satisfaction of the FDA, EMA, or comparable foreign regulatory authorities that our product candidates are safe and effective for any of their proposed indications; • the results of clinical trials may not meet the level of statistical significance required by the FDA, EMA, or comparable foreign regulatory authorities for approval, including due to the heterogeneity of patient populations; • we may be unable to demonstrate that our product candidates’ clinical and other benefits outweigh their safety risks; • the FDA, EMA, or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials; • the data collected from clinical trials of our product candidates may not be sufficient to the satisfaction of the FDA, EMA, or comparable foreign regulatory authorities to support the submission of a BLA or other comparable submission in foreign jurisdictions (e.g., MAA) or to obtain regulatory approval in the United States or elsewhere; • the FDA, EMA, or comparable foreign regulatory authorities will review extensive CMC data, our manufacturing process and inspect the relevant commercial manufacturing facility and may not approve our manufacturing process or facility; • the approval policies or regulations of the FDA, EU, or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval; and • we may be unable to agree on any required pediatric investigation plan with regulatory authorities prior to any BLA or MAA filing.
Because there is no precedent for regulatory approval of a CAR T therapy in this treatment paradigm, we may face unexpected challenges in generating sufficient clinical data to support an approval, and regulatory authorities may impose additional requirements or take longer than anticipated to evaluate our data.
Because there is no precedent for regulatory approval of a CAR T therapy in this treatment paradigm, we may face unexpected challenges in generating sufficient clinical data to 45 Table of Contents support an approval, and regulatory authorities may impose additional requirements or take longer than anticipated to evaluate our data.
Regulators in the United States are increasingly scrutinizing these statements, and if any of our privacy notices or related materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators or other adverse consequences.
Regulators in the United States are increasingly scrutinizing these statements, and if any of our privacy notices or related materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, misleading, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators 61 Table of Contents or other adverse consequences.
Our product candidates require many specialty raw materials, including viral vectors that deliver the CAR sequence and electroporation technology, some of which are manufactured by small companies with limited resources and experience to 65 Table of Contents support a commercial product, and the suppliers may not be able to deliver raw materials to our specifications.
Our product candidates require many specialty raw materials, including viral vectors that deliver the CAR sequence and electroporation technology, some of which are manufactured by small companies with limited resources and experience to support a commercial product, and the suppliers may not be able to deliver raw materials to our specifications.
Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us.
Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs 82 Table of Contents and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke third parties to assert claims against us.
For example, previously we and Servier had different interpretations regarding the respective parties’ respective rights and obligations under the Original Servier Agreement. In May 2024, we entered into the Servier Amendment which clarified each parties rights and obligations.
For example, previously we and Servier had different interpretations regarding the respective parties’ respective rights and obligations under the Original Servier Agreement. In May 2024, we entered into the Servier Amendment which clarified each party's rights and obligations.
An unfavorable outcome could result in a loss of our current patent rights and could require us to cease using the related technology or to attempt to license 77 Table of Contents rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms.
An unfavorable outcome could result in a loss of our current patent rights and could require us to cease using the related technology or to attempt to license rights to it from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms.
We may also need to raise additional capital sooner than we currently anticipate if we choose to expand more rapidly than we presently plan. In any event, we will require additional capital for the further development and commercialization of our product candidates, including funding our internal manufacturing capabilities.
We may also need to raise additional capital sooner than we currently anticipate if we choose to expand more rapidly than we presently plan. In any event, we will require 39 Table of Contents additional capital for the further development and commercialization of our product candidates, including funding our internal manufacturing capabilities.
Applicable data protection laws, privacy policies, data protection obligations and public company disclosure obligations may require us, or we may voluntarily choose, to notify relevant stakeholders, including affected individuals, regulators and investors, of certain security incidents, or to implement other requirements, such as providing credit monitoring.
Applicable data protection laws, privacy policies, data privacy and security obligations and public company disclosure obligations may require us, or we may voluntarily choose, to notify relevant stakeholders, including affected individuals, regulators and investors, of certain security incidents, or to implement other requirements, such as providing credit monitoring and identity theft protection services.
Further, we do not own or control the CLARITY assay or its regulatory approval process. As a result, we are dependent on others to complete the necessary regulatory filings, respond to inquiries from regulators, and obtain regulatory approvals, such as EU CTA approval, in a timely manner.
Further, we do not own or control the CLARITY assay or its regulatory approval process. As a result, we are dependent on others to complete the necessary regulatory filings, respond to inquiries from regulators, and obtain regulatory approvals, such as EU Clinical Trial Application (CTA) approval, in a timely manner.
For instance, the development of autologous CAR T cell therapies continues to rapidly advance, including into earlier lines of treatment of LBCL and treatment of relapsed/refractory (R/R) multiple myeloma, as described under the section entitled "Business—Competition" included in this Annual Report.
For instance, the development of autologous CAR T cell therapies continues to rapidly advance, including into earlier 50 Table of Contents lines of treatment of LBCL and treatment of relapsed/refractory (R/R) multiple myeloma, as described under the section entitled "Business—Competition" included in this Annual Report.
Our joint venture may face manufacturing difficulties, such as from changes in raw materials or processes due to local regulations, or delivering our licensed product candidates in China, Taiwan, South Korea or Singapore, which could prevent any development or commercialization of our licensed product candidates in the region.
Our joint 56 Table of Contents venture may face manufacturing difficulties, such as from changes in raw materials or processes due to local regulations, or delivering our licensed product candidates in China, Taiwan, South Korea or Singapore, which could prevent any development or commercialization of our licensed product candidates in the region.
The timeline for this approval of CLARITY in jurisdictions outside the US may be protracted due to the evolving regulatory landscape for medical devices, particularly in the EU, the complexity of demonstrating clinical utility for novel MRD assays, and potential resourcing constraints, such as within EU regulatory bodies.
The timeline for this approval of CLARITY in jurisdictions outside the U.S. may be protracted due to the evolving regulatory landscape for medical devices, particularly in the EU, the complexity of demonstrating clinical utility for novel MRD assays, and potential resourcing constraints, such as within EU regulatory bodies.
For instance, because our anti-BCMA product candidates may require a higher dose than cema-cel, it is possible that it may be more difficult to scale production of our anti-BCMA product candidates to meet demand. As a result, we may never be able to develop a commercially viable product.
For instance, because our anti-BCMA product candidates may require a higher dose than cema-cel, it is 51 Table of Contents possible that it may be more difficult to scale production of our anti-BCMA product candidates to meet demand. As a result, we may never be able to develop a commercially viable product.
Moreover, experiencing a material cybersecurity incident and any mandatory disclosures could lead to negative publicity, loss of investor or partner confidence in the effectiveness of our cybersecurity measures, diversion of management’s attention, governmental investigations, lawsuits, and the expenditure of significant capital and other resources.
Moreover, 58 Table of Contents experiencing a material cybersecurity incident and any mandatory disclosures could lead to negative publicity, loss of investor or partner confidence in the effectiveness of our cybersecurity measures, diversion of management’s attention, governmental investigations, lawsuits, and the expenditure of significant capital and other resources.
Our investigational new drug (IND) applications name specific third-party vendors to supply certain raw materials, components, technology, and services that are essential to manufacturing our product candidates. We do not have the ability to rapidly secure alternative sources for these materials or services.
Our IND applications name specific third-party vendors to supply certain raw materials, components, technology, and services that are essential to manufacturing our product candidates. We do not have the ability to rapidly secure alternative sources for these materials or services.
Increased negative public opinion or more restrictive government regulations either in the United States or internationally, would have a 71 Table of Contents negative effect on our business or financial condition and may delay or impair the development and commercialization of our product candidates or demand for such product candidates.
Increased negative public opinion or more restrictive government regulations either in the United States or internationally, would have a negative effect on our business or financial condition and may delay or impair the development and commercialization of our product candidates or demand for such product candidates.
This could lead to more severe or prolonged 47 Table of Contents toxicities or even patient deaths, which could result in us or the FDA or other comparable foreign regulatory authorities delaying, suspending, varying, or terminating one or more of our clinical trials, and which could jeopardize regulatory approval.
This could lead to more severe or prolonged toxicities or even patient deaths, which could result in us or the FDA or other comparable foreign regulatory authorities delaying, suspending, varying, or terminating one or more of our clinical trials, and which could jeopardize regulatory approval.
If observed, these differences may require additional clinical exploration and may cause delays in the execution or termination of development campaigns. See the section entitled "Business—Product Pipeline and Development Strategy" included in this Annual Report for information on safety events.
If observed, these differences may require additional clinical exploration and may cause delays in the execution or termination of development campaigns. Refer to the section entitled "Business—Product Pipeline and Development Strategy" included in this Annual Report for information on safety events.
Since patent applications in the United States and most other countries are confidential for a period of time after filing, we cannot be certain that we were the first to file any patent application related to our product candidates.
Since patent applications in the United States and most other countries are confidential for a period of time after filing, we 78 Table of Contents cannot be certain that we were the first to file any patent application related to our product candidates.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeThis team helps to identify and assess risks from cybersecurity threats by monitoring and evaluating our threat environment using various methods including, for example: automated tools, subscribing to reports and services that identify cybersecurity threats and analyzing such reports of threats and actors, conducting scans of our threat environment, evaluating threats reported to us, coordinating with law enforcement as appropriate about certain threats, having third parties conduct threat assessments, conducting vulnerability assessments, and working with third parties to conduct certain tests of our environment. 83 Table of Contents Depending on the environment and systems, we implement and maintain various technical, physical, and organizational measures, processes, standards and policies designed to manage and mitigate material risks from cybersecurity threats to our Information Systems and Data, including, for example: incident detection and response procedures; an incident response policy; a vulnerability management policy; a disaster recovery plan; conducting risk assessments; encrypting certain of our data; maintaining network security controls, segmenting certain data; maintaining access and physical security controls; asset management, tracking, and disposal protocols; systems monitoring; a assessing vendor risk; employee training; penetration testing conducted by third parties; and maintaining cybersecurity insurance.
Biggest changeDepending on the environment and systems, we implement and maintain various technical, physical, and organizational measures, processes, standards and policies designed to manage and mitigate material risks from cybersecurity threats to our Information Systems and Data, including, for example: incident detection and response procedures; an incident response policy; a vulnerability management policy; a disaster recovery plan; conducting risk assessments; encrypting certain of our data; maintaining network security controls, segmenting certain data; maintaining access and physical security controls; asset management, tracking, and disposal protocols; systems monitoring; a assessing vendor risk; employee training; penetration testing conducted by third parties; and maintaining cybersecurity insurance.
Our Vice President IT has over 20 years of experience in IT, data engineering, and data analytics. Our Vice President of IT Security is responsible for hiring appropriate personnel, helping to integrate cybersecurity risk considerations into the Company’s overall IT risk management strategy, communicating key priorities to relevant personnel, overseeing cybersecurity operations, and managing the cybersecurity technologies, processes, and projects.
Our Vice President IT has over 20 years of experience in IT, data engineering, and data analytics. Our Director of IT Security is responsible for hiring appropriate personnel, helping to integrate cybersecurity risk considerations into the Company’s overall IT risk management strategy, communicating key priorities to relevant personnel, overseeing cybersecurity operations, and managing the cybersecurity technologies, processes, and projects.
Our cybersecurity risk assessment and management processes are implemented and maintained by certain Company management, including our Director of IT Security and Vice President of IT. Our Director of IT Security has over 13 years of experience leading IT security and has certifications including CISSP and CCSP.
Our cybersecurity risk assessment and management processes are implemented and maintained by certain Company management, including our Director of IT Security and Vice President of IT. Our Director of IT Security has over 14 years of experience leading IT security and has certifications including CISSP and CCSP.
The Vice President of IT and General Counsel work with the Company’s cross functional incident response team to help the Company mitigate and remediate cybersecurity incidents of which they are notified.
The Vice President of IT and General Counsel work with the Company’s cross functional incident response team to help the Company mitigate and remediate cybersecurity incidents of which they are notified. In addition, the Company’s incident response and vulnerability management policies and procedures include reporting to the audit committee of the board of directors for certain cybersecurity incidents.
Depending on the nature of the services provided, the sensitivity of the Information Systems and Data at issue, and the identity of the provider, our vendor management process may involve different levels of assessment designed to help identify cybersecurity risks associated with a provider and impose contractual obligations related to cybersecurity on the provider.
Depending on the nature of the services provided, the sensitivity of the Information Systems and Data at issue, and the identity of the provider, our vendor management process may involve different levels of assessment designed to help identify cybersecurity risks associated with a provider and impose contractual obligations related to cybersecurity on the provider. 87 Table of Contents For a description of the risks from cybersecurity threats that may materially affect the Company and how they may do so, refer to our risk factors under Part I.
In addition, the Company’s incident response and vulnerability management policies and procedures include reporting to the audit committee of the board of directors for certain cybersecurity incidents. 84 Table of Contents The audit committee receives periodic reports from Data Management, Analytics and Integration and General Counsel concerning the Company’s significant cybersecurity threats and risk and the processes the Company has implemented to address them.
The audit committee receives periodic reports from Data Management, Analytics and Integration and General Counsel concerning the Company’s significant cybersecurity threats and risk and the processes the Company has implemented to address them. The audit committee also receives various reports, summaries or presentations related to cybersecurity threats, risk and mitigation.
Removed
For a description of the risks from cybersecurity threats that may materially affect the Company and how they may do so, see our risk factors under Part I. Item 1A.
Added
This team helps to identify and assess risks from cybersecurity threats by monitoring and evaluating our threat environment using various methods including, for example: automated tools, subscribing to reports and services that identify cybersecurity threats and analyzing such reports of threats and actors, conducting scans of our threat environment, evaluating threats reported to us, coordinating with law enforcement as appropriate about certain threats, having third parties conduct threat assessments, conducting vulnerability assessments, and working with third parties to conduct certain tests of our environment.
Removed
The audit committee also receives various reports, summaries or presentations related to cybersecurity threats, risk and mitigation.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeRegardless of outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources and other factors. Item 4. Mine Safety Disclosures. Not applicable. 85 Table of Contents PART II
Biggest changeRegardless of outcome, litigation can have an adverse impact on us because of defense and settlement costs, diversion of management resources and other factors.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeCumulative Total Return date ended 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 Allogene Therapeutics, Inc. $ 100.00 $ 97.79 $ 57.81 $ 24.37 $ 12.44 $ 8.25 S&P 500 $ 100.00 $ 116.82 $ 148.24 $ 119.42 $ 148.35 $ 184.12 Nasdaq Biotechnology $ 100.00 $ 126.49 $ 126.78 $ 111.98 $ 116.16 $ 114.57 Nasdaq Composite $ 100.00 $ 144.51 $ 175.42 $ 117.35 $ 168.31 $ 216.52 86 Table of Contents Dividend Policy We have never declared or paid any cash dividends on our capital stock.
Biggest changeCumulative Total Return date ended 12/31/2020 12/31/2021 12/31/2022 12/31/2023 12/31/2024 12/31/2025 Allogene Therapeutics, Inc. $ 100.00 $ 59.11 $ 24.92 $ 12.72 $ 8.44 $ 5.43 S&P 500 $ 100.00 $ 127.71 $ 102.88 $ 127.81 $ 157.60 $ 184.78 Nasdaq Biotechnology $ 100.00 $ 99.56 $ 87.93 $ 91.22 $ 89.52 $ 119.12 Nasdaq Composite $ 100.00 $ 122.31 $ 81.32 $ 116.64 $ 151.41 $ 181.97 90 Table of Contents Dividend Policy We have never declared or paid any cash dividends on our capital stock.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Our common stock is listed on The Nasdaq Global Select Market under the symbol “ALLO”. Holders of Common Stock As of March 7, 2025, there were approximately 62 holders of record of our common stock.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Our common stock is listed on The Nasdaq Global Select Market under the symbol “ALLO”. Holders of Common Stock As of March 10, 2026, there were approximately 62 holders of record of our common stock.
The following graph shows the value of an investment of $100 from December 31, 2019 through December 31, 2024, in our common stock, the Standard & Poor’s 500 Index (S&P 500), the Nasdaq Biotechnology Index, and Nasdaq Composite Index.
The following graph shows the value of an investment of $100 from December 31, 2020 through December 31, 2025, in our common stock, the Standard & Poor’s 500 Index (S&P 500), the Nasdaq Biotechnology Index, and Nasdaq Composite Index.

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeResults of Operations Comparison of the Years Ended December 31, 2024 and 2023 The following sets forth our results of operations for the years ended December 31, 2024 and 2023 (dollars in thousands): Year Ended December 31, Change 2024 2023 $ % Collaboration revenue - related party $ 22 $ 95 $ (73) (77) % Operating expenses: Research and development 192,299 242,914 (50,615) (21) % General and administrative 65,205 71,673 (6,468) (9) % Impairment of long-lived asset 15,717 13,245 2,472 19 % Total operating expenses 273,221 327,832 (54,611) (17) % Loss from operations (273,199) (327,737) 54,538 (17) % Other income (expense), net: Interest and other income, net 20,153 18,307 1,846 10 % Interest expense (181) — (181) (100) % Other expenses, net (3,920) (17,835) 13,915 (78) % Total other income (expense), net 16,052 472 15,580 3,301 % Loss before income taxes (257,147) (327,265) 70,118 (21) % Income tax expense (443) — (443) (100) % Net loss $ (257,590) $ (327,265) $ 69,675 (21) % Collaboration revenue - related party Revenue recognized in the years ended December 31, 2024 and 2023 was mainly due to participation in the joint steering committee performance obligation related to the License Agreement entered into with Overland Therapeutics on December 14, 2020.
Biggest changeResults of Operations Comparison of the Years Ended December 31, 2025 and 2024 The following sets forth our results of operations for the years ended December 31, 2025 and 2024: 97 Table of Contents Year Ended December 31, Change (dollars in thousands) 2025 2024 $ % Collaboration revenue - related party $ — $ 22 $ (22) (100) % Operating expenses: Research and development 150,152 192,299 (42,147) (22) % General and administrative 56,781 65,205 (8,424) (13) % Impairment of long-lived asset 2,382 15,717 (13,335) (85) % Total operating expenses 209,315 273,221 (63,906) (23) % Loss from operations (209,315) (273,199) 63,884 (23) % Other income (expense), net: Interest and other income, net 19,289 20,153 (864) (4) % Interest expense (1,075) (181) (894) 494 % Other income (expense), net 215 (3,920) 4,135 (105) % Total other income (expense), net 18,429 16,052 2,377 15 % Loss before income taxes (190,886) (257,147) 66,261 (26) % Income tax expense — (443) 443 (100) % Net loss $ (190,886) $ (257,590) $ 66,704 (26) % Collaboration revenue - related party Revenue recognized in the year ended December 31, 2024 was mainly due to participation in the joint steering committee performance obligation related to the License Agreement entered into with Overland Therapeutics on December 14, 2020.
The non-cash charges consisted primarily of stock-based compensation of $51.7 million, impairment of long-lived assets of $15.7 million, depreciation and amortization of $13.6 million, non-cash rent expense of $5.3 million, impairment of equity investment and equity method investment of $2.0 million, and share of losses from equity method investments of $1.7 million, partially offset by net amortization and accretion on investment securities of $8.3 million.
The non-cash charges consisted primarily of stock-based compensation of $51.7 million, impairment of long-lived assets of $15.7 million, depreciation and amortization of $13.6 million, non-cash rent expense of $5.3 million, impairment of equity investment of $2.0 million, and share of losses from equity method investments of $1.7 million, partially offset by net amortization and accretion on investment securities of $8.3 million.
Investing Activities During the year ended December 31, 2024, net cash provided by investing activities of $75.7 million was related to cash inflows from maturities of investments of $432.5 million and cash provided by investment sales of $5.4 million, partially offset by the purchase of investments of $361.5 million and purchases of property and equipment of $0.7 million.
During the year ended December 31, 2024, net cash provided by investing activities of $75.7 million was related to cash inflows from maturities of investments of $432.5 million and cash provided by investment sales of $5.4 million, partially offset by the purchase of investments of $361.5 million and purchases of property and equipment of $0.7 million.
Our operations have been financed primarily by net proceeds from the sale and issuance of our convertible preferred stock, the issuance of convertible promissory notes, net proceeds from our IPO, our at-the-market (ATM) offerings, our June 2020 underwritten public offering, an upfront cash payment of $40.0 million received in December 2020 pursuant to our License Agreement with Overland Therapeutics, and our May 2024 registered offering.
Our operations have been financed primarily by net proceeds from the sale and issuance of our convertible preferred stock, the issuance of convertible promissory notes, net proceeds from our IPO, our at-the-market (ATM) offerings, our June 2020 underwritten public offering, upfront cash payment of $40.0 million received in December 2020 pursuant to our License Agreement with Overland Therapeutics, and our May 2024 registered offering.
The payment obligations under the license agreements are contingent upon future events such as our achievement of specified development, regulatory and commercial milestones and we will be required to make development milestone payments and royalty payments in connection with the sale of products developed under these agreements.
The payment obligations under the license agreements are contingent upon future events such as our achievement of specified development, regulatory and/or commercial milestones and we will be required to make development milestone payments and royalty payments in connection with the sale of products developed under these agreements.
Interest Expense Interest expense related to the California Institute of Regenerative Medicine (CIRM) award is accrued upon cash receipt. Other Expenses, net Other expenses, net consist of non-operating income and expenses, including primarily our share of net losses for the period from, and impairment of, our equity method investments and impairment of our equity investments.
Interest Expense Interest expense related to the California Institute of Regenerative Medicine (CIRM) award is accrued upon cash receipt. Other Income (Expense), net Other income (expense), net, consist of non-operating income and expenses, including primarily our share of net losses for the period from, and impairment of, our equity investments.
In total, we have agreed to fund approximately $37.3 million in MRD assay development costs, milestone payments for U.S., and certain international regulatory submissions and assay utilization costs to process clinical samples. Components of Results of Operations Revenues As of December 31, 2024, our revenue has been exclusively generated from the License Agreement with Overland Therapeutics.
In total, we have agreed to fund approximately $37.3 million in MRD assay development costs, milestone payments for U.S., and certain international regulatory submissions and assay utilization costs to process clinical samples. Components of Results of Operations Revenues As of December 31, 2025, our revenue has been exclusively generated from the License Agreement with Overland Therapeutics.
Recent Accounting Pronouncements Please refer to Note 2 to our consolidated financial statements for a discussion of new accounting standards and updates that may impact us.
Recent Accounting Pronouncements Refer to Note 2 to our consolidated financial statements for a discussion of new accounting standards and updates that may impact us.
The most significant research and development expenses relate to costs incurred for the development of our most advanced product candidates and include: • expenses incurred under agreements with our collaboration partners and third-party contract organizations, investigative clinical trial sites that conduct research and development activities on our behalf, and consultants; • costs related to production of clinical materials, including fees paid for raw materials and to contract manufacturers; • laboratory and vendor expenses related to the execution of preclinical and clinical trials; • employee-related expenses, which include salaries, benefits and stock-based compensation; • facilities and other expenses, which include expenses for rent and maintenance of facilities, depreciation and amortization expense and supplies; and 91 Table of Contents • other significant research and development costs including overhead costs.
The most significant research and development expenses relate to costs incurred for the development of our most advanced product candidates and include: • expenses incurred under agreements with our collaboration partners and third-party contract organizations, investigative clinical trial sites that conduct research and development activities on our behalf, and consultants; • costs related to production of clinical materials, including fees paid for raw materials and to contract manufacturers; • laboratory and vendor expenses related to the execution of preclinical and clinical trials; • employee-related expenses, which include salaries, benefits and stock-based compensation; • facilities and other expenses, which include expenses for rent and maintenance of facilities, depreciation and amortization expense and supplies; and • other significant research and development costs including overhead costs.
Our operating lease obligations primarily consist of lease payments on our research, lab and office facilities in South San Francisco, California, as well as lease payments on our cell manufacturing facility in Newark, California. For additional information regarding our lease obligations, see Note 7 to our consolidated financial statements included elsewhere in this Annual Report.
Our operating lease obligations primarily consist of lease payments on our research, lab and office facilities in South San Francisco, California, as well as lease payments on our cell manufacturing facility in Newark, California. For additional information regarding our lease obligations, refer to Note 7 on our consolidated financial statements included elsewhere in this Annual Report.
(Notch), pursuant to which Notch granted us an exclusive, worldwide, royalty-bearing, sublicensable license under certain of Notch’s intellectual property to develop, make, use, sell, import, and otherwise commercialize therapeutic 89 Table of Contents gene-edited T cell and/or natural killer cell products from induced pluripotent stem cells directed at certain CAR targets for initial application in NHL, B-cell precursor acute lymphoblastic leukemia (ALL) and multiple myeloma.
(Notch), pursuant to which Notch granted us an exclusive, worldwide, royalty-bearing, sublicensable license under certain of Notch’s intellectual property to develop, make, use, sell, import, and otherwise commercialize therapeutic gene-edited T cell and/or natural killer cell products from induced pluripotent stem cells directed at certain CAR targets for initial application in NHL, B-cell precursor acute lymphoblastic leukemia (ALL) and multiple myeloma.
We have completed enrollment in an expansion cohort in a Phase 1b clinical trial (TRAVERSE) of ALLO-316, an allogeneic CAR T cell product candidate targeting CD70, in adult patients with advanced or metastatic clear cell renal cell carcinoma (RCC).
We have completed enrollment of 20 treated patients in an expansion cohort in a Phase 1b clinical trial (TRAVERSE) of ALLO-316, an allogeneic CAR T cell product candidate targeting CD70, in adult patients with advanced or metastatic clear cell renal cell carcinoma (RCC).
In May 2024, we entered into an Amendment and Settlement Agreement (the Servier Amendment) with Servier under which we: (1) expanded our territory under the Original Servier Agreement to include the European Union and the United Kingdom, and provides for an option to further expand our territory to include China and Japan, (2) waived certain of our rights to elect to convert certain of our license rights to a worldwide license, (3) revised our future milestone payments to coincide with Servier’s milestone payments to Cellectis under the Servier-Cellectis Agreement, (4) agreed to pre-pay a future €20 million milestone payment into an escrow account, and (5) increased the United States tiered royalty rates to a range from the low tens to the mid teen percentages, and agreed to an ex-U.S. royalty rate of 10%.
In May 2024, we entered into an Amendment and Settlement Agreement (the Servier Amendment) with Servier under which we: (1) expanded our territory under the Original Servier Agreement to include the European Union and the United Kingdom, and provided for an option to further expand our territory to include China and Japan, (2) waived certain of our rights 93 Table of Contents to elect to convert certain of our license rights to a worldwide license, (3) revised our future milestone payments to coincide with Servier’s milestone payments to Cellectis under the Servier-Cellectis Agreement, (4) agreed to pre-pay a future €20 million milestone payment into an escrow account, and (5) increased the United States tiered royalty rates to a range from the low tens to the mid teen percentages, and agreed to an ex-U.S. royalty rate of 10%.
See Note 6 to our consolidated financial statements appearing elsewhere in this Annual Report for more information related to our recognition of revenue and the License Agreement. In the future, we may generate revenue from a combination of product sales, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements or a combination of these approaches.
Refer to Note 6 on our consolidated financial statements appearing elsewhere in this Annual Report for more information related to our recognition of revenue and the License Agreement. In the future, we may generate revenue from a combination of product sales, marketing and distribution arrangements and other collaborations, strategic alliances and licensing arrangements or a combination of these approaches.
Contractual Obligations and Commitments Material Cash Commitments and Requirements Our commitments primarily consist of obligations under our agreements with Pfizer, Cellectis, Servier, Notch and Foresight. Under these agreements we are required to make milestone payments upon successful completion of certain regulatory and sales milestones on a target-by-target and country-by-country basis.
Contractual Obligations and Commitments Material Cash Commitments and Requirements Our commitments primarily consist of obligations under our agreements with Pfizer, Cellectis, Servier and Foresight. Under these agreements we are required to make milestone payments upon successful completion of certain development, regulatory and/or sales milestones on a target-by-target and country-by-country basis.
For a more detailed description of these agreements, see Note 6 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
For a more detailed description of these agreements, refer to Note 6 on our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
If, and when, we do raise additional capital through public or private equity offerings, the ownership interest of our existing stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our stockholders’ rights.
If, and when, we do raise additional capital through public or private equity offerings, the ownership interest of our existing stockholders will be diluted, and the terms of these securities may 99 Table of Contents include liquidation or other preferences that adversely affect our stockholders’ rights.
On February 19, 2025, we entered into an Amended and Restated Strategic Collaboration Agreement with Foresight Diagnostics which expands our collaboration to include the development of Foresight Diagnostics’ MRD assay as a companion diagnostic for use with cema-cel as part of a possible EU and/or UK clinical development program, and as part of an expansion of ALPHA3 to Canadian and Australian clinical trial sites in support of our US clinical development program.
On February 19, 2025, we entered into an Amended and Restated Strategic Collaboration Agreement with Foresight Diagnostics which expands our collaboration to include the development of Foresight Diagnostics’ MRD assay for use with cema-cel as part of a possible EU and/or UK clinical development program, and as part of an expansion of ALPHA3 to Canadian and Australian clinical trial sites in support of our U.S. clinical development program.
Financing Activities During the year ended December 31, 2024, net cash provided by financing activities of $116.7 million was related to net proceeds from the issuance of common stock through our May 2024 registered offering of $105.3 million, net proceeds from the issuance of common stock through ATM transactions of $6.8 million, proceeds from the CIRM award of $2.3 million, proceeds from the sale of common stock through our employee stock purchase plan of $1.5 million, and proceeds from the issuance of common stock upon exercise of stock options of $0.8 million.
During the year ended December 31, 2024, net cash provided by financing activities of $116.7 million was related to net proceeds from the issuance of common stock through our May 2024 registered offering of $105.3 million, net proceeds from the issuance of common stock through ATM transactions of $6.8 million, proceeds from the CIRM award of $2.3 million, 100 Table of Contents proceeds from the sales of common stock through our employee stock purchase plan of $1.5 million, and proceeds from the issuance of common stock upon the exercise of stock options of $0.8 million.
In connection with the Organizational Restructuring, on May 24, 2024, we and Allogene Overland PRC entered into a First Amendment to Exclusive License Agreement (the License Amendment) to amend and supplement certain provisions of the License Agreement.
In connection with the Organizational Restructuring, on May 24, 2024, we and Allogene Overland PRC entered into a First Amendment to Exclusive License Agreement (the License Amendment) to amend and supplement certain provisions of 94 Table of Contents the License Agreement.
Collaboration and License Agreement with Antion 90 Table of Contents On January 5, 2022, we entered into an exclusive collaboration and global license agreement (Antion Collaboration and License Agreement) with Antion Biosciences SA (Antion) for Antion’s miRNA technology (miCAR), to advance multiplex gene silencing as an additional tool to develop next generation allogeneic CAR T products.
Collaboration and License Agreement with Antion On January 5, 2022, we entered into an exclusive collaboration and global license agreement (Antion Collaboration and License Agreement) with Antion Biosciences SA (Antion) for Antion’s miRNA technology (miCAR), to advance multiplex gene silencing as an additional tool to develop next generation allogeneic CAR T products.
The net change in operating assets and liabilities was primarily due to deposit placed in escrow related to the Servier Amendment of $20.8 million, decrease in operating lease liabilities of $6.3 million, decrease in accounts payable of $0.5 million, increase in 95 Table of Contents prepaid expenses and other current assets of $0.5 million and decrease in accrued and other current liabilities of $1.3 million, partially offset by decrease in other long-term assets of $4.3 million, and increase in other long-term liabilities of $0.3 million.
The net change in operating assets and liabilities was primarily due to deposit placed in escrow related to the Servier Amendment of $20.8 million, decrease in operating lease liabilities of $6.3 million, decrease in accrued and other current liabilities of $1.3 million, decrease in accounts payable of $0.5 million, and increase in prepaid expense and other current assets of $0.5 million, partially offset by decrease in other long-term assets of $4.3 million and increase in other long-term liabilities of $0.3 million.
As of December 31, 2024 and 2023, we had $69.2 million and $108.7 million, respectively, of total unrecognized stock-based compensation. Impairment of Long-lived Assets Our long-lived assets, including right-of-use assets, are reviewed for impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable.
As of December 31, 2025 and 2024, we had $40.5 million and $69.2 million, respectively, of total unrecognized stock-based compensation. Impairment of Long-lived Assets Our long-lived assets, including right-of-use assets, are reviewed for impairment whenever events or changes in circumstances indicate that the carrying amount of an asset may not be recoverable.
Pursuant to the Foresight Agreement, the parties have agreed to collaborate on a non-exclusive basis in the development of Foresight Diagnostics’ MRD assay as an in vitro diagnostic to identify the MRD+ patient population to be enrolled in our ALPHA3 trial of cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A) for treatment of large B cell lymphoma (LBCL).
Pursuant to the Foresight Agreement, the parties have agreed to collaborate on a non-exclusive basis in the development of Foresight Diagnostics’ CLARITY TM MRD assay as an in vitro diagnostic to identify the MRD+ patient population to be enrolled in our ALPHA3 trial of cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A) for treatment of LBCL.
As of December 31, 2024, we were unable to estimate the timing or likelihood of achieving the milestones or making future product sales. For additional information regarding our agreements, see Note 6 to our consolidated financial statements included elsewhere in this Annual Report.
As of December 31, 2025, we were unable to estimate the timing or likelihood of achieving the milestones or making future product sales. For additional information regarding our agreements, refer to Note 6 on our consolidated financial statements included elsewhere in this Annual Report.
Operating Expenses Research and Development To date, our research and development expenses have related primarily to discovery efforts, preclinical and clinical development, and manufacturing of our product candidates. Research and development expenses for the year ended December 31, 2024 included costs associated with our clinical and preclinical stage pipeline candidates and research into newer technologies.
Operating Expenses 95 Table of Contents Research and Development To date, our research and development expenses have related primarily to discovery efforts, preclinical and clinical development, and manufacturing of our product candidates. Research and development expenses for the year ended December 31, 2025 included costs associated with our clinical and preclinical stage pipeline candidates and research into newer technologies.
In November 2019, we entered into a sales agreement with Cowen and Company, LLC (Cowen), as amended on November 2, 2022 and November 2, 2023, under which we may from time to time issue and sell shares of our common stock through Cowen in ATM offerings.
In November 2019, we entered into a sales agreement with TD Securities (U.S.A.) LLC (f/k/a Cowen and Company, LLC) (TD Cowen), as amended on November 2, 2022 and November 2, 2023, under which we may from time to time issue and sell shares of our common stock through TD Cowen in ATM offerings.
The gr ant date fair value of the stock-based awards is generally recognized on a straight-line basis over the requisite service period, which is generally the vesting period of the respective awards. 97 Table of Contents For the years ended December 31, 2024, and 2023, stock-based compensation was $51.7 million, and $66.0 million, respectively.
The gr ant date fair value of the stock-based awards is generally recognized on a straight-line basis over the requisite service period, which is generally the vesting period of the respective awards. For the years ended December 31, 2025, and 2024, stock-based compensation was $37.6 million, and $51.7 million, respectively.
We believe that the assumptions and estimates associated with accrued research and development expenditures, stock-based compensation and impairment of long-lived assets have the most significant impact on our consolidated financial statements. Therefore, we consider these to be our critical accounting policies and estimates.
We believe that the assumptions and estimates associated with accrued research and development expenditures, stock-based compensation and impairment of long-lived assets have the most significant impact on our consolidated financial statements.
The $13.9 million decrease was primarily due to lower share of net losses in our equity method investments of $9.0 million and lower impairment losses of $5.0 million related to our equity method investment and equity investment. Liquidity and Capital Resources To date, we have incurred significant net losses and negative cash flows from operations.
The $4.1 million increase was primarily due to lower impairment loss of $2.0 million related to our equity investment and lower share of net losses in our equity method investments of $1.7 million. Liquidity and Capital Resources To date, we have incurred significant net losses and negative cash flows from operations.
We believe that the aggregate of our current cash, cash 94 Table of Contents equivalents and investments available for operations will be sufficient to fund our operations for at least the next 12 months from the date this Annual Report on Form 10-K is filed with the SEC.
As of December 31, 2025, we had $258.3 million in cash, cash equivalents and investments. We believe that the aggregate of our current cash, cash equivalents and investments available for operations will be sufficient to fund our operations for at least the next 12 months from the date this Annual Report on Form 10-K is filed with the SEC.
MRD assays) in order to reach our enrollment targets; • the countries in which the trials are conducted; • the length of time required to enroll eligible patients; • the total number of cells that patients receive; • the drop-out or discontinuation rates of patients; • potential additional safety monitoring or other studies requested by regulatory agencies, including to resolve any future clinical hold; • the duration of patient follow-up; and • the efficacy and safety profile of the product candidates.
MRD assays) in order to reach our enrollment targets; • the countries in which the trials are conducted; • the length of time required to enroll eligible patients; • the total number of cells that patients receive; • the drop-out or discontinuation rates of patients; • potential additional safety monitoring or other studies requested by regulatory agencies, including to resolve any future clinical hold; • the duration of patient follow-up; and • the efficacy and safety profile of the product candidates. 96 Table of Contents In addition, the probability of success for each product candidate will depend on numerous factors, including safety, efficacy, competition, manufacturing capability and commercial viability.
Of the $123.9 million of the external expenses for the year ended December 31, 2023, $43.2 million was related to our cema-cel program. Research and development expenses were $192.3 million and $242.9 million for the years ended December 31, 2024 and 2023, respectively.
Of the $101.2 million of the external expenses for the year ended December 31, 2024, $36.4 million was related to our cema-cel program. Research and development expenses were $150.2 million and $192.3 million for the years ended December 31, 2025 and 2024, respectively.
Accrued Research and Development Costs We accrue liabilities for estimated costs of research and development activities conducted by our collaboration partners and third-party service providers, which include the conduct of preclinical and clinical studies, and contract manufacturing activities.
Therefore, we consider these to be our critical accounting policies and estimates. 101 Table of Contents Accrued Research and Development Costs We accrue liabilities for estimated costs of research and development activities conducted by our collaboration partners and third-party service providers, which include the conduct of preclinical and clinical studies, and contract manufacturing activities.
During the years ended December 31, 2024 and 2023, we sold an aggregate of 2,539,134 and 20,894,565 shares of common stock, respectively, in ATM offerings resulting in net proceeds of $6.8 million and $91.1 million, respectively.
During the years ended December 31, 2025 and 2024, we sold an aggregate of 13,430,193 and 2,539,134 shares of common stock, respectively, in ATM offerings resulting in net proceeds of $22.3 million and $6.8 million, respectively.
We have a deep pipeline of allogeneic chimeric antigen receptor (CAR) T cell product candidates targeting multiple promising antigens in a host of hematological malignancies, solid tumors and autoimmune diseases. Last year we announced our 2024 Platform Vision under which we are now focusing on three core programs.
We have a deep pipeline of allogeneic chimeric antigen receptor (CAR) T cell product candidates targeting multiple promising antigens in a host of hematological malignancies, solid tumors and autoimmune diseases. We are focusing our resources on three core programs: ALPHA3, RESOLUTION and TRAVERSE clinical trials.
The net decrease of $50.6 million was primarily due to a decrease in personnel related costs of $32.5 million, of which $11.5 million was decreased stock-based compensation expense, external costs related to the advancement of our product candidates of $12.4 million due to the timing of process development activities and manufacturing runs and facilities, depreciation, and other expense of $5.8 million.
The net decrease of $42.1 million was primarily due to a decrease in development costs of $20.9 million related to the advancement of our product candidates due to the timing of process development activities and manufacturing runs, personnel related costs of $15.3 million, of which $7.5 million was decreased stock-based compensation expense, and facilities, depreciation, and other expenses of $6.0 million.
The net change in operating assets and liabilities was primarily due to decrease in accounts payable of $7.5 million, decrease in accrued and other current liabilities of $6.8 million, decrease in operating lease liabilities of $6.0 million, increase in other long-term assets of $1.5 million and decrease in other long-term liabilities of $0.6 million, partially offset by decrease in prepaid expense and other current assets of $1.1 million.
The net change in operating assets and liabilities was primarily due to a decrease in operating lease liabilities of $7.5 million, increase in the deposit placed in escrow related to the Servier Amendment of $2.7 million, decrease in accrued and other current liabilities of $2.5 million, increase in other long-term assets of $1.3 million, and decrease in accounts payable of $1.2 million, partially offset by a decrease in prepaid expenses and other current assets of $3.2 million and increase in other long-term liabilities of $1.1 million.
Of the $101.2 million of the external expenses for the year ended December 31, 2024, $36.4 million was related to our cema-cel program. Our research and development expenses included $119.0 million of internal expenses and $123.9 million of external expenses for the year ended December 31, 2023.
Of the $74.6 million of the external expenses for the year ended December 31, 2025, $23.4 million was related to our cema-cel program. Our research and development expenses included $91.1 million of internal expenses and $101.2 million of external expenses for the year ended December 31, 2024.
Additionally, in February 2025, we entered into an Amended and Restated Strategic Collaboration Agreement with Foresight Diagnostics which expands our collaboration to enable the development of Foresight Diagnostics’ MRD assay as a companion diagnostic in the EU, UK, Canada and Australia in support of Allogene’s clinical development of cema-cel. Since inception, we have had significant operating losses.
Additionally, in February 2025, we entered into an Amended and Restated Strategic Collaboration Agreement with Foresight Diagnostics (which was acquired by Natera in December 2025 and continues to operate as a standalone subsidiary), which expands our collaboration to enable the development of Foresight Diagnostics’ MRD assay in the EU, UK, Canada and Australia in support of our clinical development of cema-cel.
We received net proceeds of $105.2 million, after deducting underwriting discounts and commissions and offering expenses payable by us. Capital Resources Our primary use of cash is for operating expenses, which consist primarily of clinical manufacturing and research and development expenditures related to our lead product candidates, other research efforts, and to a lesser extent, general and administrative expenditures.
Capital Resources Our primary use of cash is for operating expenses, which consist primarily of clinical manufacturing and research and development expenditures related to our lead product candidates, other research efforts, and to a lesser extent, general and administrative expenditures.
During the year ended December 31, 2023, net cash provided by investing activities of $163.3 million was related to cash inflows from maturities of investments of $597.8 million and cash provided by investment sales of $5.6 million, partially offset by the purchase of investments of $438.6 million and purchases of property and equipment of $1.5 million.
Investing Activities During the year ended December 31, 2025, net cash provided by investing activities of $95.6 million was related to cash inflows from maturities of investments of $234.2 million partially offset by the purchase of investments of $138.3 million and purchases of property and equipment of $0.4 million.
License Agreement with Allogene Overland Biopharm (PRC) Co., Limited On December 14, 2020, we entered into a License Agreement with Allogene Overland Biopharm (CY) Limited (Allogene Overland) (the License Agreement), a joint venture established by us and Overland Pharmaceuticals (CY) Inc.
In August 2025 the Company extended the term of the agreement for an additional year. License Agreement with Overland Therapeutics, Inc. On December 14, 2020, we entered into a License Agreement with Allogene Overland Biopharm (CY) Limited (Allogene Overland) (the License Agreement), a joint venture established by us and Overland Pharmaceuticals (CY) Inc.
On October 6, 2020, we announced we entered into a strategic five-year collaboration agreement with MD Anderson for the preclinical and clinical investigation of allogeneic CAR T cell product candidates. We and MD Anderson are collaborating on the design and conduct of preclinical and clinical studies with oversight from a joint steering committee.
On October 6, 2020, we announced we entered into a strategic five-year collaboration agreement with MD Anderson for the preclinical and clinical investigation of allogeneic CAR T cell product candidates. In August 2025 we extended the term of the agreement for an additional year.
Impairment of long-lived asset During the year ended December 31, 2024, we recorded impairments as the carrying values of sublet property asset groups were not recoverable due to the market conditions. During the year ended December 31, 2024, we recognized total impairment charge of $15.7 million.
During the year ended December 31, 2024, we recorded long-lived asset total impairment charges of $15.7 million as the carrying values of sublet property asset groups were not recoverable due to market conditions. Interest and Other Income, Net Interest and other income, net was $19.3 million and $20.2 million for the years ended December 31, 2025 and 2024, respectively.
The development of our other product candidates is currently focused on pre-clinical studies, including studies of BCMA and DLL3 CARs with and without our CD70 Dagger® protein, and various manufacturing improvements that may be applicable to such product candidates, we continue to explore opportunities to partner with collaborators on product candidates across our pipeline. 88 Table of Contents In May 2024, we entered into an Amendment and Settlement Agreement (the Servier Amendment) under which we expanded the geographic territory for our CD19 license to include the European Union and the United Kingdom.
The development of our other product candidates is currently focused on pre-clinical studies, including studies of BCMA and DLL3 CARs with and without our CD70 Dagger® protein technology, and 92 Table of Contents various manufacturing improvements that may be applicable to such product candidates. We continue to explore opportunities to partner with collaborators on product candidates across our pipeline.
During the year ended December 31, 2023, cash used in operating activities of $237.7 million was attributable to a net loss of $327.3 million, substantially offset by non-cash charges of $110.8 million and a net change of $21.3 million in our net operating assets and liabilities.
During the year ended December 31, 2024, cash used in operating activities of $200.3 million was attributable to a net loss of $257.6 million and a decrease of $24.8 million in our net operating assets and liabilities, partially offset by non-cash charges of $82.1 million.
The specified dollar limit on the amount of common stock that may be sold under the sales agreement was removed pursuant to the November 2, 2023 amendment to the sales agreement. In May 2024, we completed an underwritten offering pursuant to which we issued and sold 37,931,035 shares of our common stock.
The specified dollar limit on the amount of common stock that may be sold under the sales agreement was removed pursuant to the November 2, 2023 amendment to the sales agreement.
General and administrative costs are expensed as incurred, and we accrue for services provided by third parties related to the above expenses by monitoring the status of services provided and receiving estimates from our service providers, and adjusting our accruals as actual costs become known. 92 Table of Contents Other Income (Expense), Net: Interest and Other Income, Net Interest and other income, net primarily consists of interest earned on our cash and cash equivalents and investments, as well as investment gains and losses recognized during the period.
General and administrative costs are expensed as incurred, and we accrue for services provided by third parties related to the above expenses by monitoring the status of services provided and receiving estimates from our service providers, and adjusting our accruals as actual costs become known.
During the year ended December 31, 2023, net cash provided by financing activities of $95.7 million was related to net proceeds from the issuance of common stock through ATM transactions of $91.1 million, proceeds from the sales of common stock through our employee stock purchase plan of $2.5 million, and proceeds from the issuance of common stock upon the exercise of stock options of $2.1 million.
Financing Activities During the year ended December 31, 2025, net cash provided by financing activities of $30.2 million was related to net proceeds from the issuance of common stock through ATM transactions of $22.4 million, proceeds from the CIRM award of $6.9 million, and proceeds from the sale of common stock through our employee stock purchase plan of $0.9 million.
Cash Flows The following table summarizes our cash flows for the periods indicated: Year Ended December 31, 2024 2023 (in thousands) Net cash (used in) provided by: Operating activities $ (200,300) $ (237,733) Investing activities 75,688 163,289 Financing activities 116,675 95,695 Net increase (decrease) in cash, cash equivalents and restricted cash $ (7,937) $ 21,251 Operating Activities During the year ended December 31, 2024, cash used in operating activities of $200.3 million was attributable to a net loss of $257.6 million, substantially offset by non-cash charges of $82.1 million and a net change of $24.8 million in our net operating assets and liabilities.
Cash Flows The following table summarizes our cash flows for the periods indicated: Year Ended December 31, 2025 2024 (in thousands) Net cash (used in) provided by: Operating activities $ (149,246) $ (200,300) Investing activities 95,559 75,688 Financing activities 30,157 116,675 Net decrease in cash, cash equivalents and restricted cash $ (23,530) $ (7,937) Operating Activities During the year ended December 31, 2025, cash used in operating activities of $149.2 million was attributable to a net loss of $190.9 million and a decrease of $10.9 million in our net operating assets and liabilities, partially offset by non-cash charges of $52.5 million.
The non-cash charges consisted primarily of stock-based compensation of $66.0 million, depreciation and amortization of $14.2 million, impairment of long-lived assets of $13.2 million, share of losses from equity method investments of $10.7 million, impairment of equity investment and equity method investment of $7.0 million, net amortization and accretion on investment securities of $6.8 million, and non-cash rent expense of $6.6 million.
The non-cash charges consisted primarily of stock-based compensation of $37.6 million, depreciation and amortization of $12.4 million, non-cash rent expense of $4.4 million, and impairment of long-lived assets of $2.4 million, partially offset by net amortization and accretion on investment securities of $4.2 million.
We made an upfront payment of $3.0 million to MD Anderson in the year ended December 31, 2020 and made an additional upfront payment of $3.0 million to MD Anderson in October 2023.
Payment of this funding is contingent on mutual agreement to study orders in order for any study to be included under the alliance. We made an upfront payment of $3.0 million to MD Anderson in the year ended December 31, 2020 and made additional upfront payments of $3.0 million to MD Anderson in October 2023 and June 2025.
Strategic Collaboration Agreement with Foresight Diagnostics On January 3, 2024, we entered into a Strategic Collaboration Agreement (the Foresight Agreement) with Foresight Diagnostics, Inc. (Foresight Diagnostics).
Strategic Collaboration Agreement with Foresight Diagnostics On January 3, 2024, we entered into a Strategic Collaboration Agreement (the Foresight Agreement) with Foresight Diagnostics, Inc. (Foresight Diagnostics). In December 2025, Foresight Diagnostics was acquired by Natera and continues to operate as a standalone subsidiary.
Interest and Other Income, Net Interest and other income, net was $20.2 million and $18.3 million for the years ended December 31, 2024 and 2023, respectively. The $1.9 million increase was primarily due to higher yields and a corresponding increase in the interest earned on our cash, cash equivalents and investments.
The $0.9 million decrease was primarily due to lower yields and a corresponding decrease in the interest earned on our cash, cash equivalents and investments. Interest expense Interest expense was related to the CIRM award proceeds received for the years ended December 31, 2025 and 2024.
In January 2025, we announced that the FDA has cleared our investigational new drug (IND) application for a Phase 1 rheumatology basket study of ALLO-329 (RESOLUTION trial). Our RESOLUTION trial will evaluate the safety and efficacy of ALLO-329 across multiple autoimmune diseases, including systemic lupus erythematosus (SLE) (including lupus nephritis), idiopathic inflammatory myopathies, and systemic sclerosis.
In January 2025, we announced that the FDA had cleared our investigational new drug (IND) application for a Phase 1 rheumatology basket study of ALLO-329 (RESOLUTION trial), which we initiated in the second quarter of 2025.
Our net loss was $257.6 million for the year ended December 31, 2024. As of December 31, 2024, we had an accumulated deficit of $1.8 billion. As of December 31, 2024, we had $373.1 million in cash and cash equivalents and investments and we expect our cash runway to fund operations into the second half of 2026.
As of December 31, 2025, we had an accumulated deficit of $2.0 billion. As of December 31, 2025, we had $258.3 million in cash and cash equivalents and investments and we expect our cash runway to fund operations into the first quarter of 2028.
Research and Development Expenses The following table shows the primary components of our research and development expenses for the periods presented: 93 Table of Contents Year Ended December 31, 2024 2023 Change Personnel $ 79,993 $ 112,457 $ (32,464) Development costs 62,264 74,644 (12,380) Facilities and depreciation 40,941 44,684 (3,743) Other 9,101 11,129 (2,028) Total research and development expenses 192,299 242,914 (50,615) Our research and development expenses included $91.1 million of internal expense and $101.2 million of external expenses for the year ended December 31, 2024.
Research and Development Expenses The following table shows the primary components of our research and development expenses for the periods presented: Year Ended December 31, 2025 2024 Change (in thousands) Personnel $ 64,677 $ 79,993 $ (15,316) Development costs 41,411 62,264 (20,853) Facilities and depreciation 37,001 40,941 (3,940) Other 7,063 9,101 (2,038) Total research and development expenses 150,152 192,299 (42,147) Our research and development expenses included $75.5 million of internal expense and $74.6 million of external expenses for the year ended December 31, 2025.
The net decrease of $6.5 million was primarily due to a decrease in personnel related costs of $5.3 million, of which $2.7 million was decreased stock-based compensation expense, and a decrease in legal and professional services of $1.2 million.
General and Administrative Expenses 98 Table of Contents General and administrative expenses were $56.8 million and $65.2 million for the years ended December 31, 2025 and 2024, respectively. The net decrease of $8.4 million was primarily due to a decrease in personnel related costs of $7.4 million, of which $6.6 million was decreased stock-based compensation expense.
While we have additional programs in our pipeline, our clinical development priorities are focused on cema-cel (1L Consolidation), ALLO-316 and ALLO-329.
On April 27, 2025, we announced that ALLO-329 had received three Fast Track Designations (FTD) from the FDA for the treatment of adult patients with SLE, IIM, and SSc. While we have additional programs in our pipeline, our clinical development priorities are focused on cema-cel (1L consolidation), ALLO-316 and ALLO-329.
Later this year, we plan to seek scientific advice from European and UK regulatory authorities to assist us with finalizing our regulatory strategy for the EU and the UK.
We have met with European Union (EU) regulatory authorities and have received scientific advice to assist us with finalizing our regulatory strategy for opening the trial in the EU, and operational feasibility assessments for both the EU and United Kingdom (UK) are ongoing.
In June 2024, we initiated a pivotal Phase 2 clinical trial (ALPHA3) for cema-cel as part of a first line (1L) treatment plan for newly diagnosed and treated LBCL patients who are likely to relapse and need further therapy, and we now have 40 sites activated.
In June 2024, we initiated a pivotal Phase 2 clinical trial (ALPHA3) evaluating cemacabtagene ansegedleucel (cema-cel, previously ALLO-501A) as part of a first-line (1L) consolidation treatment for patients newly diagnosed with large B-cell lymphoma (LBCL) who, despite initial treatment success, remain at high risk for relapse.
Interest expense Interest expense was related to the CIRM award proceeds received for the year ended December 31, 2024. No such interest expense was recorded for the year ended December 31, 2023. Other expenses, net Other expenses, net were $3.9 million and $17.8 million for the years ended December 31, 2024 and 2023, respectively.
Other Income (Expense), net Other income was $0.2 million for the year ended December 31, 2025 and other expense was $3.9 million for the year ended December 31, 2024.
On October 29, 2024, we announced that we had received Regenerative Medicine Advanced Therapy (RMAT) designation for ALLO-316 for adult patients with advanced or metastatic RCC. We have implemented a protocol amendment that incorporates a diagnostic and treatment algorithm into the study design.
The Phase 1b expansion cohort evaluated ALLO-316 administered as a single dose of 80 million CAR T cells following a standard lymphodepletion regimen (fludarabine 30 mg/m²/day and cyclophosphamide 500 mg/m²/day for three days). On October 29, 2024, we announced that we had received Regenerative Medicine Advanced Therapy (RMAT) designation for ALLO-316 for adult patients with advanced or metastatic RCC.
For more information, see “Risk Factors— Servier’s discontinuation of its involvement in the development of CD19 Products and Servier's disputes with Cellectis, or future disputes with us, may have adverse consequences." Collaboration and License Agreement with Notch On November 1, 2019, we entered into a Collaboration and License Agreement (the Notch Agreement) with Notch Therapeutics Inc.
Collaboration and License Agreement with Roche (formerly Notch) On November 1, 2019, we entered into a Collaboration and License Agreement (the Notch Agreement) with Notch Therapeutics Inc.
Removed
We are currently focused on developing cemacabtagene ansegedleucel (cema-cel, previously ALLO-501A) in large B-cell lymphoma (LBCL).
Added
A trial-in-progress poster highlighting ALPHA3 was presented at the 2025 Annual Meeting of the American Society of Clinical Oncology (ASCO, June 1, 2025). We now have over 60 activated trial sites in the United States and Canada. Additional sites in Australia and South Korea are progressing toward activation in mid-2026.
Removed
The design of the ALPHA3 1L consolidation trial builds upon the results demonstrated in the Phase 1 ALPHA2 trial and leverages an investigational diagnostic test developed by Foresight Diagnostics, Inc. that we believe will identify patients who have achieved remission by standard disease assessment but who have minimal residual disease (MRD) at the completion of 1L chemoimmunotherapy.
Added
The ALPHA3 trial design expands on findings from our Phase 1 ALPHA2 study and incorporates an investigational diagnostic developed by Foresight Diagnostics, Inc., which was acquired by Natera, Inc. (Natera) in December 2025 and continues to operate as a standalone subsidiary.
Removed
The ALPHA3 trial is designed to study the impact of treating MRD positive patients with cema-cel. The study will randomize approximately 240 patients who achieve a complete response or partial response to 1L therapy, but who are MRD positive. Patients will be randomized to receive either consolidation with cema-cel or the current standard of care, which is observation.
Added
This diagnostic test identifies patients who, despite achieving remission according to standard evaluations, remain at risk due to minimal residual disease (MRD) following 1L chemoimmunotherapy. Patients eligible for enrollment include those who achieve either a complete response or a near-complete partial response to initial treatment and would otherwise be monitored through observation as the current standard of care.
Removed
The study design, which has event free survival (EFS) as its primary endpoint, initially includes two lymphodepletion arms: – FCA: standard fludarabine and cyclophosphamide plus ALLO-647 – FC: standard fludarabine and cyclophosphamide without ALLO-647 87 Table of Contents One of these lymphodepletion arms will be discontinued following a planned interim analysis designed to identify the most appropriate regimen for this patient population.
Added
The trial’s primary endpoint is event-free survival (EFS).
Removed
An initial safety and futility interim analysis will occur once 12 patients in each arm have been enrolled and followed for MRD conversion.
Added
Initially, the trial was designed to randomize approximately 240 MRD-positive patients into one of three arms: (1) cema-cel therapy following lymphodepletion with standard fludarabine and cyclophosphamide (FC arm), (2) cema-cel therapy 91 Table of Contents following lymphodepletion with fludarabine, cyclophosphamide, and ALLO-647 (an anti-CD52 monoclonal antibody) (FCA arm), or (3) standard-of-care observation (control arm).
Removed
If both treatment arms perform better than the control arm according to the futility criteria, but neither treatment arm shows a trend toward superiority relative to the other in this interim analysis, additional patients may be enrolled and analyzed before we select the final lymphodepletion regimen.
Added
On August 1, 2025, we announced that we selected standard fludarabine and cyclophosphamide (FC) as the lymphodepletion regimen. This lymphodepletion regimen selection was made in conjunction with the ALPHA3 Data and Safety Monitoring Board (DSMB) and Steering Committee and following consultation with the U.S. Food and Drug Administration (FDA). The FCA arm is now closed to further enrollment.
Removed
The selection of the lymphodepletion regimen is anticipated around mid-2025, depending on the interim analyses results and overall trial progress.
Added
This decision, made ahead of the scheduled futility analysis, was prompted by a Grade 5 adverse event in the FCA arm that has been attributed to the use of ALLO-647. The event occurred on Day 54 post-infusion from hepatic failure, believed to have resulted from disseminated adenovirus infection in the setting of immune suppression.
Removed
Efficacy analyses are expected to occur in 2026, and will include the Independent Data Safety Monitoring Board (IDSMB) interim EFS analysis in the first half of 2026 and the data readout of the primary EFS analysis is expected around year-end 2026. A biologics license application (BLA) submission is targeted for 2027.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeAs of December 31, 2024, 2024, we had $20.8 million of deposit placed in escrow. As of December 31, 2024, we had no receivables and $0.1 million of current liabilities denominated in foreign currency. 98 Table of Contents
Biggest changeAs of December 31, 2025, we 102 Table of Contents had $23.5 million of deposit placed in escrow. As of December 31, 2025, we had $0.2 million receivables and $0.1 million of current liabilities denominated in foreign currency. 103 Table of Contents
A 10% change in the interest rates in effect on December 31, 2024 would not have had a material effect on the fair market value of our cash equivalents and available-for-sale securities.
A 10% change in the interest rates in effect on December 31, 2025 would not have had a material effect on the fair market value of our cash equivalents and available-for-sale securities.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk. Interest Rate Risk Our cash, cash equivalents and investments of $373.1 million as of December 31, 2024, consist of bank deposits, money market funds and available-for-sale securities. Such interest-earning instruments carry a degree of interest rate risk; however, historical fluctuations in interest income have not been significant for us.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk. Interest Rate Risk Our cash, cash equivalents and investments of $258.3 million as of December 31, 2025, consist of bank deposits, money market funds and available-for-sale securities. Such interest-earning instruments carry a degree of interest rate risk; however, historical fluctuations in interest income have not been significant for us.

Other ALLO 10-K year-over-year comparisons