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• Our clinical trials may fail to demonstrate the safety and efficacy of any of our product candidates, which would prevent or delay regulatory approval and commercialization.
−Removed: • No CAR T therapy has been approved as a part of first-line consolidation strategy for the treatment of LBCL patients, which presents significant regulatory, commercial, and operational risks, and there is no assurance of success in this unproven setting.
+Added: • Risks related to serious adverse events (SAEs) in the discontinued fludarabine, cyclophosphamide, and ALLO-647 (FCA) arm of our ALPHA3 trial, including the Grade 5 SAE, could lead to regulatory actions, negative perceptions, and potential product liability claims.
+Added: • No CAR T therapy has been approved as a part of first-line consolidation strategy for the treatment of large B-cell lymphoma (LBCL) patients, which presents significant regulatory, commercial, and operational risks, and there is no assurance of success in this unproven setting.
• We may encounter substantial delays in our clinical trials, or may not be able to conduct our trials on the timelines we expect.
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• Gene-editing is a relatively new technology, and if we are unable to use this technology in our intended product candidates, our revenue opportunities will be materially limited.
+Added: • There is uncertainty regarding whether the use of fludarabine and cyclophosphamide (FC) without ALLO-647 will achieve sufficient lymphodepletion to support the efficacy of our allogeneic CAR T product candidate in the ALPHA3 trial.
• We are heavily reliant on our partners, Cellectis and Servier, for access to TALEN gene editing technology for the manufacturing and development of our oncology product candidates.
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The occurrence of any of the following risks could harm our business, financial condition, results of operations and/or growth prospects or cause our actual results to differ materially from those contained in forward-looking statements we have made in this report and those we may make from time to time.
−Removed: You should consider all of the risk factors
−Removed: described below when evaluating our business.
+Added: You should consider all of the risk factors described below when evaluating our business.
The risk factors set forth below that are marked with an asterisk (*) contain changes to the similarly titled risk factors included in, or did not appear as separate risk factors in, Item 1A of our Annual Report, which was filed with the SEC on March 13, 2025.
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For the year ended December 31, 2024, we reported a net loss of $257.6 million.
−Removed: For the three months ended March 31, 2025, we reported a net loss of $59.7 million.
−Removed: As of March 31, 2025, we had an accumulated deficit of $1.9 billion.
+Added: For the six months ended June 30, 2025, we reported a net loss of $110.7 million.
+Added: As of June 30, 2025, we had an accumulated deficit of $1.9 billion.
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.
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Further, if approved, we will require significant additional capital in order to launch and commercialize our product candidates.
−Removed: As of March 31, 2025, we had $335.5 million in cash and cash equivalents and investments.
+Added: As of June 30, 2025, we had $302.6 million in cash and cash equivalents and investments.
Changing circumstances may cause us to consume capital significantly faster than we currently anticipate, and we may need to spend more money than currently expected because of circumstances beyond our control.
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To the extent that we raise additional capital through the sale of equity or convertible debt securities or to the extent that we may issue equity securities in connection with a strategic transaction, the ownership interest of our stockholders will be diluted.
−Removed: If we are unable to raise
−Removed: additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development or commercialization of our product candidates or other research and development initiatives.
+Added: If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we may have to significantly delay, scale back or discontinue the development or commercialization of our product candidates or other research and development initiatives.
Our license agreements may also be terminated if we are unable to meet the payment obligations under the agreements.
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In addition, since we are in the early stages of clinical development, we do not know all the doses to be evaluated in pivotal trials or, if approved, commercially.
−Removed: Finding a suitable dose for our cell therapy product candidates as well as ALLO-647 may delay our anticipated clinical development timelines.
−Removed: These unknowns and other emerging findings from our clinical trials may result in protocol amendments, which may result in additional costs and may also delay our anticipated
−Removed: clinical development timelines.
+Added: Finding a suitable dose for our cell therapy product candidates may delay our anticipated clinical development timelines.
+Added: These unknowns and other emerging findings from our clinical trials may result in protocol amendments, which may result in additional costs and may also delay our anticipated clinical development timelines.
+Added: For example, our decision to terminate the FCA arm (fludarabine, cyclophosphamide, and ALLO-647) in our ALPHA3 trial resulted in a protocol amendment that has resulted in additional costs and could delay our anticipated clinical development
In addition, our expectations with regard to our scalability and costs of manufacturing may vary significantly as we develop our product candidates and understand these critical factors.
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In addition, we are reliant on Foresight Diagnostics to perform MRD testing.
−Removed: 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.
+Added: 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.
The clinical study requirements of the FDA, European Medicines Agency (EMA) and other comparable foreign regulatory authorities and the criteria these regulators use to determine the safety and efficacy of a product candidate are determined according to the type, complexity, novelty and intended use and market of the potential products.
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For example, the regulatory approval process for cema-cel based on our ALPHA3 trial is more complex because the regulatory agencies may require us to pair the approval of cema-cel with a companion diagnostic test.
−Removed: We also face additional challenges in obtaining regulatory approval for ALLO-647, which we use as part of our lymphodepletion regimen, and for which we would seek to obtain approval concurrently with approval of a CAR T cell product candidate.
Approvals by the European Commission and FDA for existing autologous CAR T therapies, such as Kymriah® and Yescarta®, may not be indicative of what these regulators may require for approval of our therapies.
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For instance, allogeneic product candidates may result in graft-versus-host disease (GvHD) or chromosomal abnormalities not experienced with autologous products.
−Removed: Additionally, any Phase 2 trial results, such as in the ALPHA3 trial, may not be representative of Phase 1 results,
−Removed: which were based on limited patients and a patient population in an advanced stage or LBCL, and such Phase 2 trial results may not be accepted by the FDA as pivotal and sufficient for cema-cel approval, requiring us to open additional trials to establish that cema-cel is safe and effective.
−Removed: Even if we collect promising initial clinical data of our product candidates, longer-term data may reveal new adverse events or responses that are not durable.
+Added: Additionally, any Phase 2 trial results, such as in the ALPHA3 trial, may not be representative of Phase 1 results, which were based on limited patients and a patient population in an advanced stage or LBCL, and such Phase 2 trial results may not be accepted by the FDA as pivotal and sufficient for cema-cel approval, requiring us to open additional trials to establish that cema-cel is safe and effective.
+Added: Even if we collect promising initial clinical data of our product candidates, longer-term data
+Added: may reveal new adverse events or responses that are not durable.
Unexpected clinical outcomes would significantly impact our business.
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Results of our clinical trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics.
−Removed: Approved autologous CAR T therapies and those under development have shown frequent rates of CRS, neurotoxicity including immune effector cell-associated neurotoxicity syndrome (ICANS), serious infections, prolonged cytopenia and hypogammaglobulinemia, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), immune effector cell-associated HLH-like syndrome (IEC-HS) and adverse events have resulted in the death of patients.
+Added: Approved autologous CAR T therapies and those under development have shown frequent rates of CRS, neurotoxicity including ICANS, serious infections, prolonged cytopenia and hypogammaglobulinemia, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), immune effector cell-associated HLH-like syndrome (IEC-HS) and adverse events have resulted in the death of patients.
We have observed certain of these adverse events for our allogeneic CAR T product candidates.
Other adverse events could also emerge in autologous CAR T therapies over time.
−Removed: instance, patients who received an autologous anti-BCMA CAR T cell therapy have experienced neurocognitive and hypokinetic movement disorder with features of Parkinson’s disease that emerged months after treatment and may have been due to BCMA expression within the brain.
+Added: For instance, patients who received an autologous anti-BCMA CAR T cell therapy have experienced neurocognitive and hypokinetic movement disorder with features of Parkinson’s disease that emerged months after treatment and may have been due to BCMA expression within the brain.
Our anti-BCMA product candidates have the risk of causing similar adverse events.
In January 2024 the FDA sent letters to all companies with approved autologous CAR T therapies requesting them to add a black box warning on the label of their autologous CAR T therapies.
−Removed: The FDA is requiring label updates to include a black box warning that T-cell malignancies may occur following treatment with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies.
+Added: The FDA is requiring label updates to include a black box warning that T-cell malignancies may occur following treatment with BCMA- and CD19-directed genetically
+Added: modified autologous T-cell immunotherapies.
The required warnings are specific to autologous therapies.
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Our allogeneic CAR T cell product candidates may also cause unique adverse events related to the differences between the donor and patients, such as GvHD or infusion reactions.
−Removed: In addition, we utilize a lymphodepletion regimen, which generally includes combinations of fludarabine, cyclophosphamide and ALLO-647, that may cause serious adverse events.
+Added: In addition, we utilize a lymphodepletion regimen that caused serious adverse events.
For instance, because some regimens are expected to cause a deep and sometimes prolonged immune suppression, patients will have an increased risk of infection that may be unable to be cleared by the patient and ultimately lead to other serious adverse events or death.
+Added: For example, a patient death occurred in the FCA arm (fludarabine, cyclophosphamide, and ALLO-647) of our ALPHA3 trial.
+Added: This Grade 5 SAE, which occurred on Day 54 post-infusion, involved fulminant hepatic failure caused by disseminated adenovirus infection, potentially worsened by acetaminophen toxicity.
+Added: The depth of immunosuppression likely associated with ALLO-647 is believed to have increased susceptibility to this viral infection.
Our lymphodepletion regimen has caused such adverse events and may also cause prolonged cytopenia and aplastic anemia.
−Removed: We are also exploring various dosing strategies for lymphodepletion in our clinical trials, such as including varying doses of the chemotherapy agents and/or ALLO-647 or eliminating one or more of the agents, which may alter the risk of serious adverse events or have other undesirable outcomes such as a reduction of the efficacy of treatment.
+Added: We have previously explored and may in the future explore various dosing strategies for lymphodepletion in our clinical trials, such as including varying doses of the chemotherapy agents and/or other components, or eliminating one or more of the agents, which may alter the risk of SAEs or have other undesirable outcomes such as a reduction of the efficacy of treatment.
In our and Servier's clinical trials of allogeneic CAR T product candidates, the most common severe or life-threatening adverse events resulted from CRS, serious infections, febrile neutropenia, prolonged cytopenia including prolonged pancytopenia, haemophagocytic lymphohistiocytosis, hypokalemia, multiple organ dysfunction syndrome, neutropenic sepsis and aplastic anemia.
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We may also combine the use of our product candidates with other investigational or approved therapies that may cause separate adverse events or events related to the combination.
−Removed: If unacceptable toxicities arise in the development of our product candidates, we could suspend or terminate our trials or the FDA or comparable foreign regulatory authorities could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications.
+Added: If unacceptable toxicities arise in the development of our product candidates, we could suspend or terminate a development program, a trial or certain arms of a trial, or the FDA or comparable foreign regulatory authorities could order us to cease clinical trials or deny approval of our product candidates for any or all targeted indications.
+Added: For example, as a result of the Grade 5 SAE in the ALPHA3 trial described above, we have terminated the FCA arm of the ALPHA3 trial, and the trial will now move forward as a two arm trial under which patients will be randomized equally (1:1) into either the FC lymphodepletion arm or standard-of-care observation.
+Added: Additionally, we have terminated all further development of ALLO-647.
Any data safety monitoring board may also 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.
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In addition, for any trials that may be completed, we cannot guarantee that the FDA or comparable foreign regulatory authorities will interpret the results as we do, and more trials could be required before we submit our product candidates for approval.
−Removed: 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.
+Added: 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.
Additionally, although the EMA has previously granted Marketing Authorizations for products even when their clinical development programs did not involve any European sites, the regulatory landscape for CAR T products continues to evolve, and the EMA may require us to conduct clinical trials in the EU in order to obtain approval.
To the extent that the results of the trials are not satisfactory to the FDA or comparable foreign regulatory authorities for support of a marketing application, approval of our product candidates may be significantly delayed, or we may be required to expend significant additional resources, which may not be available to us, to conduct additional trials in support of potential approval of our product candidates.
+Added: Risks related to SAEs in the discontinued FCA arm of our ALPHA3 trial, including the Grade 5 SAE, could lead to regulatory actions, negative perceptions, and potential product liability claims.*
+Added: Although the FCA arm of our ALPHA3 clinical trial has been terminated following a Grade 5 SAE, patients who previously received the FCA regimen remain at risk for experiencing further SAEs.
+Added: Both the previously observed Grade 5 SAE and any additional SAEs that may occur could prompt regulatory authorities, including the FDA, to request additional safety data, require enhanced patient monitoring, or impose other conditions or restrictions on our clinical program.
+Added: Such regulatory actions could delay our clinical development timelines, increase operational costs, and impact our ability to efficiently progress our trials.
+Added: Additionally, such SAEs could adversely affect perceptions among physicians and patients, potentially limiting future enrollment in ongoing or planned studies and affecting the market acceptance of our therapies.
+Added: Furthermore, such SAEs may expose us to potential product liability claims, which could materially harm our reputation, financial condition, and business prospects.
No CAR T therapy has been approved as part of a first-line consolidation strategy for the treatment of LBCL patients, which presents significant regulatory, commercial, and operational risks, and there is no assurance of success in this unproven setting.
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The success of our clinical trial and potential approval in this setting is also dependent on factors outside of our control, such as evolving treatment paradigms, competitive developments, and changes in clinical practice.
−Removed: 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.
+Added: If we are unable to
+Added: 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.
−Removed: 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.
+Added: In certain foreign jurisdictions, such as the European Union (EU), we anticipate that the CLARITY assay will be regulated as an in vitro diagnostic medical device.
The timeline for this approval of CLARITY in jurisdictions outside the U.S.
−Removed: 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.
+Added: 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.
Further, we do not own or control the CLARITY assay or its regulatory approval process.
−Removed: 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.
+Added: 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.
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.
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We may not be able to submit INDs or equivalent foreign applications to commence additional clinical trials on the timelines we expect, and even if we are able to, the FDA or other comparable foreign regulatory authorities may not permit us to proceed.*
−Removed: We plan to submit INDs or IND amendments and equivalent foreign applications for additional product candidates or indications in the future.
−Removed: We cannot be sure that submission of an IND or IND amendment or an equivalent foreign application will result in the FDA or other comparable foreign regulatory authorities allowing testing and clinical trials to begin, or that, once begun, issues will not arise that suspend or terminate such clinical trials.
+Added: We plan to submit investigational new drug (IND) applications or IND amendments and equivalent foreign applications for current and potentially new product candidates or indications in the future.
+Added: We cannot be sure that submission of an IND or IND amendment or an equivalent foreign application will result in the FDA or other comparable foreign regulatory authorities allowing testing and clinical trials to begin on our anticipated timelines, if at all, or that, once begun, issues will not arise that suspend or terminate such clinical trials.
The manufacturing of allogeneic CAR T cell therapy remains an emerging and evolving field.
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Additionally, even if such regulatory authorities agree with the design and implementation of the clinical trials set forth in an IND, IND amendment or clinical trial application, we cannot guarantee that such regulatory authorities will not change their requirements in the future.
−Removed: In addition, we have an open IND for ALLO-647, which is being used as part of lymphodepletion in certain of our clinical trials.
−Removed: Any regulatory issues related to ALLO-647 or to the development of ALLO-647, if it is used as part of a lymphodepletion regimen in a clinical study, could delay such study and delay the development of our allogeneic CAR T cell product candidates and significantly affect our business.
+Added: In addition, we have an open IND for ALLO-647, which was being used as part of lymphodepletion in certain of our clinical trials.
+Added: Currently, we have no further plans to use ALLO-647 in any current or future clinical trial.
We may encounter substantial delays in our clinical trials, or may not be able to conduct our trials on the timelines we expect.*
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We cannot guarantee that any clinical studies will be conducted as planned or completed on schedule, if at all.
−Removed: Even if our trials begin as planned, issues may arise that could suspend or terminate such clinical trials.
+Added: 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.
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a negative finding from an inspection of our or our collaborator’s clinical study operations or our study sites;
−Removed: developments on trials conducted by competitors for related technology that raises FDA or other comparable foreign regulatory authority concerns about
−Removed: risk to patients of the technology broadly;
+Added: 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;
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For example, emerging safety and efficacy outcomes could lead us to impose, tighten or expand “cutoff” values of CD70 expression to determine enrollment eligibility for TRAVERSE.
−Removed: Assay performance or necessary changes we or our partners make to the assay(s) during development may reduce the pace of enrollment or may lead to alterations in the expected benefit risk profile as compared to results collected prior to the change.
+Added: Assay performance or necessary changes we or our partners make to the assay(s) during development may reduce
+Added: the pace of enrollment or may lead to alterations in the expected benefit risk profile as compared to results collected prior to the change.
The diagnostic assay itself may not perform as expected due to identifiable or obscure factors.
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The number of patients may turn out to be lower than expected.
−Removed: Additionally, the potentially addressable patient population for our product candidates may be limited, such as due to the eligibility criteria of our trials (e.g., MRD+ rates lower than expected), or may not be amenable to treatment with our product candidates, all of which may negatively impact the potential market opportunity for our other product candidates, if approved.
+Added: Additionally, the potentially addressable patient population for our product candidates may be limited, such as due to the eligibility criteria of our trials (e.g., MRD+ rates lower than expected), or
+Added: may not be amenable to treatment with our product candidates, all of which may negatively impact the potential market opportunity for our other product candidates, if approved.
We may fail to successfully manufacture our product candidates, operate our own manufacturing facility, or obtain regulatory approval to utilize or commercialize from our manufacturing facility or at a CDMO, which could adversely affect our clinical trials and the commercial viability of our product candidates.
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Until we complete our clinical trials, we cannot be sure that the manufacturing processes employed by us or the technologies that we incorporate for manufacturing will result in consistent T cell production that will be safe and effective.
−Removed: 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.
+Added: 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.
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.
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Reduced manufacturing operations may limit our ability to timely support our development programs.*
−Removed: We have recently made the decision to reduce activities within our manufacturing operations, and focus our resources on our ongoing clinical programs, which resulted in a reduction in force (RIF).
+Added: In May 2025, we made the decision to reduce activities within our manufacturing operations, and focus our resources on our ongoing clinical programs, which resulted in a reduction in force (Workforce Reduction).
While we believe we currently hold sufficient inventory of cema-cel, ALLO-329, and ALLO-316 to meet our near-term clinical needs, including completing our current ALPHA3, RESOLUTION and TRAVERSE trials, this operational scale-down introduces several risks that could adversely affect our business in both the near and long term.
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We are highly dependent on our management, including our Executive Chair, our President and Chief Executive Officer, our Executive Vice President, Research & Development and Chief Medical Officer, our Senior Vice President and Chief Technical Officer, our Chief Financial Officer, and our General Counsel.
−Removed: The loss of the services of any of our executive officers, other key employees, and other scientific and medical advisors, and our inability to find suitable replacements could result in delays in product development and harm our business.
+Added: The loss of the services of any of our executive officers, other key employees, and
+Added: other scientific and medical advisors, and our inability to find suitable replacements could result in delays in product development and harm our business.
We conduct substantially all of our operations at our facilities in the San Francisco Bay area.
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The value to employees of stock options and RSU awards that vest over time or upon achieving goals have been significantly affected by movements in our stock price that are beyond our control and may at any time be insufficient to counteract more lucrative offers from other companies.
−Removed: We completed an option exchange program in July 2022 to alleviate the significant
−Removed: number of employee options that were underwater at that time.
+Added: We completed an option exchange program in July 2022 to alleviate the significant number of employee options that were underwater at that time.
Our stock price has significantly declined since the option exchange program and a significant number of our employee options remain underwater and may not provide the intended incentive for employees to remain at our company.
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Our success also depends on our ability to continue to attract, retain and motivate highly skilled junior, mid-level and senior managers as well as junior, mid-level and senior scientific and medical personnel.
−Removed: Our reduction in force undertaken to extend our cash runway and focus more of our capital resources on our prioritized research and development programs might not achieve our intended outcome.*
+Added: Our Workforce Reduction undertaken to extend our cash runway and focus more of our capital resources on our prioritized research and development programs might not achieve our intended outcome.*
In May 2025, our board of directors approved an approximately 28% reduction in our employee workforce in connection with a reduction in manufacturing operations and a reprioritization of resources to focus on our clinical programs.
−Removed: The reduction in force may result in unintended consequences and costs, such as the loss of institutional knowledge and expertise, attrition beyond the intended number of employees, decreased morale among our remaining employees, and the risk that we may not achieve the anticipated benefits of the reduction in force.
+Added: The Workforce Reduction may result in unintended consequences and costs, such as the loss of institutional knowledge and expertise, attrition beyond the intended number of employees, decreased morale among our remaining employees, and the risk that we may not achieve the anticipated benefits of the Workforce Reduction.
In addition, while positions have been eliminated, certain functions necessary to our operations remain, and, to the extent required, we might not successfully distribute the duties and obligations of our terminated employees among our remaining employees.
The reduction in workforce could also make it difficult for us to pursue, or prevent us from pursuing, new opportunities and initiatives due to insufficient personnel, or require us to incur additional and unanticipated costs to hire new personnel to pursue such opportunities or initiatives.
−Removed: If we are unable to realize the anticipated benefits from the reduction in force, or if we experience significant adverse consequences from the reduction in force, our business, financial condition and results of operations may be materially adversely affected.
+Added: If we are unable to realize the anticipated benefits from the Workforce Reduction, or if we experience significant adverse consequences from the Workforce Reduction, our business, financial condition and results of operations may be materially adversely affected.
The size of our workforce has fluctuated and we will need to manage the size of our organization as we continue to advance our product candidates.*
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There can be no assurance that the services of independent organizations, advisors and consultants will continue to be available to us on a timely basis when needed, or that we can find qualified replacements.
−Removed: We may also be subject to penalties or other liabilities if we mis-classify employees as consultants.
+Added: may also be subject to penalties or other liabilities if we mis-classify employees as consultants.
In addition, if we are unable to effectively manage our outsourced activities or if the quality or accuracy of the services provided by consultants is compromised for any reason, our clinical trials may be extended, delayed or terminated, and we may not be able to obtain regulatory approval of our product candidates or otherwise advance our business.
There can be no assurance that we will be able to manage our existing consultants or find other competent outside contractors and consultants on economically reasonable terms, or at all.
−Removed: If we are not able to effectively expand our organization by hiring and retaining employees and expanding our groups of consultants and contractors, we may not be able to successfully implement the tasks necessary to further develop, manufacture and commercialize our product candidates and, accordingly, may not achieve our research, development,
−Removed: manufacturing and commercialization goals.
+Added: If we are not able to effectively expand our organization by hiring and retaining employees and expanding our groups of consultants and contractors, we may not be able to successfully implement the tasks necessary to further develop, manufacture and commercialize our product candidates and, accordingly, may not achieve our research, development, manufacturing and commercialization goals.
Conversely, if we expand ahead of our business progress, we may take on unnecessary costs.
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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.
−Removed: The joint venture will also require significant operational and financial support in the future by us or third parties, and any future financing of the joint venture would increase our
−Removed: expenses or dilute our ownership in the joint venture.
+Added: The joint venture will also require significant operational and financial support in the future by us or third parties, and any future financing of the joint venture would increase our expenses or dilute our ownership in the joint venture.
We may also face unknown liabilities due to supporting our joint venture, such as due to any misuse of materials supplied to our joint venture.
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Significant political, trade, regulatory developments, and other circumstances beyond our control, including as a result of recently announced tariffs, could have a material adverse effect on our financial condition or results of operations.*
−Removed: Significant political, trade, or regulatory developments in the jurisdictions in which we develop our product candidates, such as those stemming from the change in the U.S.
−Removed: federal government, are difficult to predict and may have a material adverse effect on us.
−Removed: Similarly, changes in U.S.
−Removed: federal policy that affect the geopolitical landscape could give rise to circumstances outside our control that could have negative impacts on our business operations.
−Removed: government has recently announced substantial new tariffs affecting a wide range of products and jurisdictions and has indicated an intention to continue developing new trade policies, including with respect to the pharmaceutical industry.
−Removed: In response, certain foreign governments have announced or implemented retaliatory tariffs and other protectionist measures.
+Added: Significant political, trade, or regulatory developments in the jurisdictions in which we develop our product candidates, such as those stemming from U.S.
+Added: federal policy shifts, are difficult to predict and may have a material adverse effect on us.
+Added: Policy shifts that affect the geopolitical landscape could give rise to circumstances outside our control that could have negative impacts on our business operations.
+Added: In April 2025, the U.S.
+Added: government announced substantial new tariffs and indicated an intention to continue developing new trade policies, including with respect to the pharmaceutical industry.
+Added: In response, certain foreign governments announced or implemented retaliatory tariffs and other protectionist measures.
+Added: Since then, the U.S.
+Added: government has announced various trade deals and ongoing negotiations with other countries/regions that will move down the tariff levels in certain areas.
+Added: In August 2025, however, the U.S.
+Added: government announced new tariffs affecting a wide array of countries, including a baseline tariff of approximately 10–15%, with country-specific rates reaching as high as 25–39%, potentially impacting pharmaceutical imports from regions such as the EU under a new trade agreement.
+Added: As relevant policies are rapidly evolving, it may be difficult to evaluate their potential future impacts, and we will closely monitor these policy changes and their potential impact.
These developments have created a dynamic and unpredictable trade landscape, which may adversely impact our business, results of operations, financial condition and prospects.
+Added: In addition, the Bureau of Industry and Security, U.S.
+Added: Department of Commerce, has initiated an investigation to determine whether pharmaceutical ingredients, including finished drug product, manufactured outside the United States pose a national security risk and should be subject to additional tariffs.
We operate in a global economy, which includes utilizing third-party suppliers in several countries outside the United States.
−Removed: Although we have no near-term needs for raw materials, we have historically relied upon, and may in the future rely on, third parties for third-party contractors to manufacture cGMP raw materials that are used for the manufacturing of our product candidates.
+Added: Although we currently have no near-term needs for raw materials, we have historically relied upon, and may in the future rely on, third parties for third-party contractors to manufacture cGMP raw materials that are used for the manufacturing of our product candidates.
Current or future tariffs may result in increased research and development expenses, including with respect to increased costs associated with raw materials, laboratory equipment and research materials and components.
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In the past few years, numerous U.S.
−Removed: states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights concerning their personal data.
+Added: states have enacted comprehensive privacy laws that impose certain obligations on covered businesses, including providing specific disclosures in privacy notices and affording residents with certain rights
+Added: concerning their personal data.
As applicable, such rights may include the right to access, correct, or delete certain personal data, and to opt-out of certain data processing activities, such as targeted advertising, profiling, and automated decision-making.
The exercise of these rights may impact our business and ability to provide our products and services.
−Removed: Certain states also
−Removed: impose stricter requirements for processing certain personal data, including sensitive information, such as conducting data privacy impact assessments.
+Added: Certain states also impose stricter requirements for processing certain personal data, including sensitive information, such as conducting data privacy impact assessments.
These state laws allow for statutory fines for noncompliance.
27 unchanged sentences
We publish privacy notices and other statements regarding data privacy and security.
−Removed: 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
−Removed: or other adverse consequences.
+Added: 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,
+Added: unfair, misleading, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators or other adverse consequences.
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.
42 unchanged sentences
Our inability to obtain sufficient product liability insurance at an acceptable cost to protect against potential product liability claims could prevent or inhibit the commercialization of products we develop, alone or with corporate collaborators.
−Removed: Our insurance policies may also have various exclusions, and we may be subject to a product liability claim for which we have
+Added: Our insurance policies may also have various exclusions, and we may be subject to a product liability claim for which we have no coverage.
While we have obtained and expect to obtain clinical trial insurance for our clinical trials, we may have to pay amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we may not have, or be able to obtain, sufficient capital to pay such amounts.
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• 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;
−Removed: • 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;
+Added: • 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;
8 unchanged sentences
In our ALPHA2 trial, we observed a chromosomal abnormality, and the FDA placed our clinical trials on hold following this observation.
−Removed: While our investigation concluded that gene editing was not responsible for the chromosomal abnormality and the hold was resolved, we
−Removed: may discover future abnormalities caused by gene editing or other factors that would impact our development plans.
+Added: While our investigation concluded that gene editing was not responsible for the chromosomal abnormality and the hold was resolved, we may discover future abnormalities caused by gene editing or other factors that would impact our development plans.
The gene editing of our product candidates may also not be successful in limiting the risk of GvHD or premature rejection by the patient.
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If we are unable to maintain technological advancements consistent with industry standards, our operations and financial condition may be adversely affected.
+Added: There is uncertainty regarding whether the use of FC without ALLO-647 will achieve sufficient lymphodepletion to support the efficacy of our allogeneic CAR T product candidate in the ALPHA3 trial.*
+Added: Our ALPHA3 clinical trial is now proceeding exclusively with a lymphodepletion regimen consisting of FC without ALLO-647, and there is uncertainty regarding whether FC alone will achieve sufficient lymphodepletion to support the efficacy of our allogeneic CAR T therapy, cema-cel.
+Added: Previously, the FCA regimen was anticipated to enhance CAR T cell expansion and persistence by reducing host immune system interference;
+Added: however, the FCA arm was terminated following a Grade 5 SAE.
+Added: Although initial MRD conversion data from the FC arm suggests potential efficacy, this preliminary data is limited, and derived from a small patient cohort.
+Added: Therefore, there remains a risk that the FC lymphodepletion regimen alone may not sufficiently suppress the patient’s immune system to allow adequate expansion, persistence, and efficacy of the CAR T cells, potentially resulting in suboptimal clinical outcomes.
+Added: If the FC regimen proves inadequate, we may be required to amend the study design to enhance lymphodepletion, which could significantly delay the completion of the trial.
+Added: This risk, and any resulting delays, could materially impact our clinical trial success, regulatory approval prospects, and overall business and financial performance.
We are heavily reliant on our partners, Cellectis and Servier, for access to TALEN gene editing technology for the manufacturing and development of our oncology product candidates.*
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Anti-CD52 monoclonal antibodies deplete CD52 expressing T cells in patients while sparing therapeutic allogeneic T cells lacking CD52.
−Removed: By administering an anti-CD52 antibody prior to infusing our oncology product candidates, we believe we have the potential to reduce the likelihood of a patient’s immune system from rejecting the engineered allogeneic T cells for a sufficient period of time to enable a window of persistence during which the engineered allogeneic T cells can actively target and destroy the cancer cells.
−Removed: However, the antibody may not have the benefits that we anticipate and could have adverse effects.
We rely on an agreement with Cellectis for exclusive rights to use TALEN technology for 15 select cancer targets, including BCMA, FLT3, CD70, DLL3, Claudin 18.2 and other targets included in our pipeline.
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Cellectis has challenged and may in the future challenge certain performance by Servier, such as its development of products licensed under the Cellectis-Servier Agreement in acute lymphoblastic leukemia, and any failure by those parties to resolve such matters may have an adverse impact on us.
−Removed: If our agreements were terminated, we would be required to seek other gene editing technology or abandon our cema-cel and ALLO-316 programs, both of which could materially impact our business and financial position.
+Added: There is an ongoing arbitration between Cellectis and Servier regarding this dispute under which Cellectis is seeking to terminate the Cellectis-Servier Agreement, which would automatically terminate our sublicense from Servier.
+Added: Although both the Cellectis-Servier Agreement and our Servier sublicense provide that in the event of termination of the
+Added: Cellectis-Servier Agreement, Cellectis agrees to enter into good faith negotiations with us for a direct license on terms substantially similar in scope and grant, there can be no assurance that we will be able to obtain such a direct license.
+Added: If our agreements were terminated and we were unable to obtain a new license, we would be required to seek other gene editing technology or abandon our cema-cel or ALLO-316 programs, both of which could materially impact our business and financial position.
Further, alternative gene editing technology may not be available to us on reasonable terms, or at all, and advancing other gene editing technology would require significant resources.
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Our reliance on specific vendors named in our INDs subject us to risks if these vendors are unable or unwilling to fulfill their obligations or if we need to change vendors, which could delay or prevent the development of our product candidates and commercialization, if approved.
−Removed: 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.
+Added: 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.
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Under the Servier Agreement, Servier sublicenses to us certain rights it has licensed from Cellectis relating to Cellectis’ TALEN gene editing technology pursuant to the Servier-Cellectis Agreement.
−Removed: In May 2024 we entered into the Servier Amendment which made various amendments to the Original Servier Agreement, and expanded our licensed territory thereunder to include the European Union and the United Kingdom, and also granted us an option, under certain circumstances, to expand the territory further to include China (including Hong Kong) and Japan.
+Added: In May 2024 we entered into the Servier Amendment which made various amendments to the Original Servier Agreement, and expanded our licensed territory thereunder to include the European Union and the United Kingdom, and also
+Added: granted us an option, under certain circumstances, to expand the territory further to include China (including Hong Kong) and Japan.
Although we believe that we and Servier are both in full compliance of our respective obligations under the Servier Agreement, there can be no assurance that we will not have future disputes with Servier regarding our respective rights and obligations under our agreements and any future dispute could jeopardize our CD19 Products license, the loss of which would have a significant adverse impact on our business, financial condition, and prospects.
−Removed: In March 2025 Cellectis filed a Form 20-F with the SEC, stating that Cellectis does not believe that:
+Added: Cellectis has publicly stated that it does not believe that:
(1) the Servier-Cellectis Agreement permits Servier to grant a world-wide sub-license to us;
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Cellectis has initiated an arbitration proceeding against Servier through the Centre de Médiation et d'Arbitrage de Paris, wherein Cellectis is seeking a decision terminating the Servier-Cellectis Agreement, and seeking certain compensation.
+Added: In its Form 6-K filed with the SEC on August 4, 2025, Cellectis noted that the arbitral decision is expected to be rendered on or before December 15, 2025.
Cellectis has asserted that a favorable determination by the arbitral tribunal, if achieved, would return development and commercialization rights for the licensed products back to Cellectis.
1 unchanged sentence
Additionally, although we believe the Servier-Cellectis Agreement grants Servier the right to grant sublicenses without further consent from Cellectis, there is a risk that Cellectis may challenge the expansion of our territory under the Servier Agreement to regions outside the U.S.
−Removed: The Servier Agreement provides us with certain rights to obtain a direct license
−Removed: with Cellectis in the event the Servier-Cellectis Agreement is terminated, however, there can be no assurance that we will be able to obtain such a direct license.
+Added: The Servier Agreement provides us with certain rights to obtain a direct license with Cellectis in the event the Servier-Cellectis Agreement is terminated, however, there can be no assurance that we will be able to obtain such a direct license.
Additionally, although the Servier-Cellectis Agreement grants Servier the right to grant sublicenses without further consent from Cellectis, there is a risk that Cellectis could seek to challenge the expansion of our rights under the Servier Agreement to include the European Union and the United Kingdom.
The termination of the Servier-Cellectis Agreement, our failure to obtain a direct license with Cellectis after such termination, or a successful challenge to the territorial expansion of our rights under the Servier Agreement would have a significant adverse impact on our business, financial condition, and prospects.
−Removed: Our oncology development strategy relies on incorporating an anti-CD52 monoclonal antibody as part of the lymphodepletion preconditioning regimen prior to infusing allogeneic CAR T cell product candidates.
−Removed: Certain of our oncology product candidates utilize an anti-CD52 monoclonal antibody as part of a lymphodepletion regimen to be infused prior to infusing our product candidates.
+Added: Our oncology development strategy previously relied on incorporating an anti-CD52 monoclonal antibody as part of the lymphodepletion preconditioning regimen prior to infusing allogeneic CAR T cell product candidates.*
+Added: Previously, certain of our oncology product candidates utilized an anti-CD52 monoclonal antibody (ALLO-647) as part of a lymphodepletion regimen to be infused prior to infusing our product candidates.
The anti-CD52 antibody may reduce the likelihood of a patient’s immune system rejecting the engineered allogeneic T cells for a sufficient period of time to enable a window of persistence during which such engineered allogeneic T cells can actively target and destroy cancer cells.
However, the antibody may not have the benefits that we anticipate and could have adverse effects.
−Removed: For instance, our lymphodepletion regimen, including using an anti-CD52 antibody, will cause immune suppression that can be of unpredictable depth and duration and that may be associated with an increased risk of infection, such as to common viral or bacterial or opportunistic pathogens, that may be unable to be cleared and ultimately lead to other serious adverse events or death.
+Added: For instance, our lymphodepletion regimen, including using an anti-CD52 antibody, will cause immune suppression that can be of unpredictable depth and duration and that may be associated with an increased risk of infection, such as to common viral or bacterial or opportunistic pathogens, that may be unable to be cleared and ultimately lead to other SAEs or death.
In the prior CALM and PALL trials, a commercially available monoclonal antibody, alemtuzumab, that binds CD52 was used.
3 unchanged sentences
The EMA also recommended that alemtuzumab only be given in a hospital with ready access to intensive care facilities and specialists who can manage serious adverse reactions.
−Removed: The use of our anti-CD52 antibody may result in the same or similar adverse events as alemtuzumab, and we have chosen to administer our product candidates at trial centers experienced at managing patients with advanced malignancies as well as toxicities associated with immunomodulatory therapies, which significantly limits the sites that are eligible to participate in our clinical trials.
−Removed: If the EMA or other regulatory agencies further limit the use of alemtuzumab or anti-CD52 antibodies, our clinical program would be adversely affected.
−Removed: To secure our own readily available source of anti-CD52 antibody, we are developing our own monoclonal anti-CD52 antibody, ALLO-647, which we use in certain of our clinical trials.
−Removed: ALLO-647 may cause serious adverse events that alemtuzumab may cause, including fatal adverse events, infusion related reactions, immune thrombocytopenia, glomerular nephropathies, thyroid disorders, autoimmune cytopenias, autoimmune hepatitis, hemophagocytic lymphohistiocytosis, acquired hemophilia, infections, stroke, and progressive multifocal leukoencephalopathy.
−Removed: In addition, we are exploring various dosing strategies for lymphodepletion in our clinical trials, such as including varying doses of the chemotherapy agents and/or ALLO-647 or eliminating one or more of the agents, which may alter the risk of serious adverse events or have other undesirable outcomes such as a reduction of the efficacy of treatment.
−Removed: Additionally, our experimental lymphodepletion regimens may show different safety profiles when paired with different allogeneic CAR T product candidates such that regimens deemed safe with one CAR T product candidate may be determined to be associated with unacceptable toxicity when combined with another CAR T candidate or with the same candidate in a different patient population.
+Added: The previous use of our anti-CD52 antibody may result in the same or similar adverse events as alemtuzumab.
+Added: To secure our own readily available source of anti-CD52 antibody, we were previously developing our own monoclonal anti-CD52 antibody, ALLO-647, which we used in certain of our clinical trials.
+Added: ALLO-647 may cause SAEs that alemtuzumab may cause, including fatal adverse events, infusion related reactions, immune thrombocytopenia, glomerular nephropathies, thyroid disorders, autoimmune cytopenias, autoimmune hepatitis, hemophagocytic lymphohistiocytosis, acquired hemophilia, infections, stroke, and progressive multifocal leukoencephalopathy.
+Added: For example, a patient death occurred in the recently discontinued FCA arm of our ALPHA3 trial.
+Added: This Grade 5 SAE, which occurred on Day 54 post-infusion, involved fulminant hepatic failure caused by disseminated adenovirus infection, potentially worsened by acetaminophen toxicity.
+Added: The depth of immunosuppression likely associated with ALLO-647 is believed to have increased susceptibility to this viral infection.
+Added: In addition, we may explore various dosing strategies for lymphodepletion in our clinical trials, such as including varying doses of the chemotherapy agents and/or other agents or eliminating one or more of the agents, which may alter the risk of SAEs or have other undesirable outcomes such as a reduction of the efficacy of treatment.
+Added: Additionally, our experimental lymphodepletion regimens may show different safety profiles when paired with different allogeneic CAR T product candidates such that regimens deemed safe with one CAR T product candidate may be determined to be associated with
+Added: unacceptable toxicity when combined with another CAR T candidate or with the same candidate in a different patient population.
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 our Annual Report for information on safety events.
−Removed: If we are unable to successfully develop and manufacture ALLO-647 in the timeframe we anticipate, or at all, such as if regulatory authorities do not agree with our selected dose or approve of the use of ALLO-647 in combination with our allogeneic T cell product candidates, our clinical trial timelines and ability to commercialize certain of our oncology product candidates would be significantly delayed.
Risks Related to Our Reliance on Third Parties
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We rely on third parties to manufacture and store our clinical product supplies, and we may have to rely on third parties to produce and process our product candidates, if approved.*
−Removed: While we utilize CF1 for clinical manufacturing of our CAR T product candidates, we will continue to use CDMOs to manufacture ALLO-647 and several core reagents, and for distribution logistics.
+Added: While we utilize CF1 for clinical manufacturing of our CAR T product candidates, we will continue to use CDMOs to manufacture several core reagents, and for distribution logistics.
There can be no assurance that we will not experience supply or manufacturing issues related to our product candidates or core reagents in the future.
−Removed: We do not have long-term agreements in place with CDMOs for the manufacture of our cell therapies or of ALLO-647.
+Added: We do not have long-term agreements in place with CDMOs for the manufacture of our cell therapies.
If we are unable to contract with CDMOs on acceptable terms or at all, our clinical development program would be delayed and our business would be significantly harmed.
−Removed: For example, in December 2024 Novo Holdings completed its acquisition of Catalent, Inc., and shortly thereafter Novo Nordisk acquired three Catalent fill-finish sites and related assets from Novo Holdings.
−Removed: ALLO-647 is manufactured at one of these sites, and we have been advised by Novo Nordisk that we will need to transfer such manufacturing to a different site.
−Removed: Although we believe that we currently have sufficient ALLO-647 inventory for our near-term requirements, the transfer to a new manufacturing site will be time consuming, costly, and subject to uncertainty.
−Removed: In addition, the transfer will require regulatory approval.
−Removed: We may be unable to complete the manufacturing site transfer in a timely manner, if at all, which could significantly delay our clinical development timelines.
−Removed: If we are unable to establish an alternative manufacturing site or unable to do so in a timely manner, if at all, it could significantly delay our clinical development timelines.
−Removed: We have built CF1 and have transitioned the manufacturing of certain product candidates to our manufacturing facility, and we are reliant on CF1 as our sole manufacturing site for certain of our product candidates.
−Removed: Manufacturing product candidates in our own facility requires that we meet certain regulatory conditions, which may delay or extend our clinical trial timelines.
−Removed: 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.
+Added: We have built CF1 and have transitioned the manufacturing of our product candidates to our manufacturing facility, and we are reliant on CF1 as our sole manufacturing site for our product candidates.
+Added: Manufacturing product candidates in our
+Added: own facility requires that we meet certain regulatory conditions, which may delay or extend our clinical trial timelines.
+Added: 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.
Any disruptions to CF1’s operations, whether due to regulatory non-compliance, supply chain constraints, equipment failures, natural disasters, or other unforeseen circumstances, could have a material adverse effect on our ability to manufacture our products and meet clinical or commercial demand.
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Our contract manufacturers would also be subject to the same risks we face in developing our own manufacturing capabilities, as described above.
−Removed: 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.
+Added: 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.
In addition, our CDMOs have certain responsibilities for storage of raw materials and in the past have lost or failed to adequately store our raw materials.
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Unlike autologous CAR T companies, we are reliant on receiving healthy donor material to manufacture our product candidates.
−Removed: Healthy donor T cells vary in type and quality, and this variation makes producing standardized product candidates more difficult and makes the development and commercialization pathway of those product candidates more uncertain.
+Added: Healthy donor T cells vary in type and quality, and this variation makes producing standardized product candidates
+Added: more difficult and makes the development and commercialization pathway of those product candidates more uncertain.
We have developed a screening process designed to enhance the quality and consistency of T cells used in the manufacture of our CAR T cell product candidates, but the manufacturing runs we have completed and tested in the clinic are limited across our product candidates.
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As a result of any such contamination or injury, we may incur liability or local, city, state or federal authorities may curtail the use of these materials and interrupt our business operations.
−Removed: In the event of an accident, we could be held liable for damages or penalized with fines, and the liability could exceed our
+Added: In the event of an accident, we could be held liable for damages or penalized with fines, and the liability could exceed our resources.
We do not have any insurance for liabilities arising from medical or hazardous materials.
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These various regulatory review committees and advisory groups and new or revised guidelines that they promulgate from time to time may lengthen the regulatory review process, require us to perform additional studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval limitations or restrictions.
−Removed: Because the regulatory landscape for our CAR T cell immunotherapy product candidates is new, we may face even more cumbersome and complex regulations than those emerging for gene therapy products and cell therapy products.
+Added: Because the regulatory landscape for our CAR T cell immunotherapy product candidates is new, we may face even more cumbersome and complex regulations than
+Added: those emerging for gene therapy products and cell therapy products.
Furthermore, even if our product candidates obtain required regulatory approvals, such approvals may later be withdrawn as a result of changes in regulations or the interpretation of regulations by applicable regulatory agencies.
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• the inability to resolve any future clinical hold;
−Removed: • the FDA, EMA, or comparable foreign regulatory authorities may disagree with the design or implementation of our clinical trials;
+Added: • 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;
6 unchanged sentences
• we may be unable to agree on any required pediatric investigation plan with regulatory authorities prior to any BLA filing.
−Removed: We may be unable to obtain regulatory approval for ALLO-647 in a timely manner or at all, which could delay any approval or commercialization of our allogeneic T cell product candidates.
−Removed: As we are concurrently developing ALLO-647 to be used as part of the lymphodepletion regimen for certain of our allogeneic CAR T cell product candidates, mapping a co-development path for dual approval of ALLO-647 and any of our CAR T cell product candidates and coordinating concurrent review with different divisions of competent regulatory authorities create additional regulatory uncertainty for us and may delay the development of our product candidates.
−Removed: As an example, coordinating concurrent review with the divisions of the FDA creates such regulatory uncertainty and may delay the development of our product candidates.
−Removed: We expect the Center for Drug Evaluation and Research division of the FDA to exercise authority over the regulatory approval of ALLO-647 while the CBER division will oversee the regulatory approval of our allogeneic CAR T cell product candidates.
−Removed: In addition, the FDA is requiring us to demonstrate the overall contribution of ALLO-647 to the benefit to risk ratio of the lymphodepletion regimen for cema-cel.
−Removed: We plan to assess ALLO-647 through part one of the ALPHA3 trial.
−Removed: Some clinical trial sites may elect not to participate, and we cannot be certain when or whether we will be able to successfully enroll the ALPHA3 trial in a timely manner or that the outcome of this study will support FDA approval of both cema-cel and ALLO-647.
−Removed: Any delays to ALLO-647 approval could delay any approval or commercialization of our allogeneic CAR T cell product candidates.
−Removed: We anticipate that the EMA, or comparable foreign regulatory authorities will impose equivalent obligations as part of the marketing authorization process in their territory.
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.*
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Any delay or failure by us or third-party collaborators to develop or obtain regulatory approval (or clearance, or certification) of a companion diagnostic could delay or prevent approval or continued marketing of our related product candidates.
−Removed: We, or our collaborators, may also experience delays in developing a sustainable,
−Removed: reproducible, and scalable manufacturing process for the companion diagnostic or in transferring that process to commercial partners or negotiating insurance reimbursement plans, all of which may prevent us from completing our clinical trials or commercializing our product candidates, if approved, on a timely or profitable basis, if at all.
+Added: We, or our collaborators, may also experience delays in developing a sustainable, reproducible, and scalable manufacturing process for the companion diagnostic or in transferring that process to commercial partners or negotiating insurance reimbursement plans, all of which may prevent us from completing our clinical trials or commercializing our product candidates, if approved, on a timely or profitable basis, if at all.
Our ALPHA3 trial design requires the use of an MRD assay, and we are conducting the trial with the use of Foresight Diagnostics’ PhasED-Seq™ Circulating Tumor DNA Platform.
4 unchanged sentences
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.*
−Removed: We have received Regenerative Medicine Advanced Therapy (RMAT) designation for cema-cel, ALLO-316, and ALLO-715 and fast track designation for ALLO-316, ALLO-329, and ALLO-647.
+Added: 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.
There is no assurance that we will be able to obtain RMAT designation or fast track designation for any of our additional product candidates.
−Removed: RMAT designation and fast track designation do not change the FDA’s standards for product approval, and there is no assurance that such designation will result in expedited review or approval or that the approved indication will not be narrower than the indication covered by the designation.
+Added: RMAT designation and fast track designation do not change the FDA’s standards for product approval, and there is no assurance that such designation will result in expedited review or approval or that the approved indication will not be narrower than the indication covered by the
Additionally, RMAT designation and fast track designation can be revoked if the criteria for eligibility cease to be met as clinical data emerges.
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We plan to seek orphan drug designation for additional product candidates in specific orphan indications in which there is a medically plausible basis for the use of these products, but may never receive such designations.
−Removed: Some of our product candidates target indications
−Removed: that are not orphan indications.
+Added: Some of our product candidates target indications that are not orphan indications.
In addition, even with orphan drug designation, exclusive marketing rights in the United States may be limited if we seek approval for an indication broader than the orphan designated indication and may be lost if the FDA later determines that the request for designation was materially defective or if we are unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition, or if a subsequent applicant demonstrates clinical superiority over our products, if approved.
21 unchanged sentences
The market exclusivity period prevents a successful generic or biosimilar applicant from commercializing its product in the European Union until 10 years have elapsed from the initial marketing authorization of the reference product in the EU.
−Removed: The overall ten-year period may, occasionally, be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic
−Removed: indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
+Added: The overall ten-year period may, occasionally, be extended for a further year to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.
However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical/biological entity, and products may not qualify for data exclusivity.
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We expect downward pressure on pharmaceutical pricing to continue.
−Removed: Further, coverage policies and third-party reimbursement rates may change at
+Added: Further, coverage policies and third-party reimbursement rates may change at any time.
Even if favorable coverage and reimbursement status is attained for one or more products for which we receive regulatory approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
4 unchanged sentences
Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors, which may adversely affect our future profitability.
+Added: The current administration is pursuing policies to reduce regulations and expenditures across government including at the U.S.
+Added: Department of Health and Human Services (HHS), the FDA, the Centers for Medicare & Medicaid Services and related agencies.
+Added: These actions, presently directed by executive orders or memoranda from the Office of Management and Budget, may propose policy changes that create additional uncertainty for our business.
+Added: These actions include, for example, directing HHS and other agencies to lower prescription drug costs through a variety of initiatives, including by improving upon the Medicare Drug Price Negotiation Program and establishing “Most-Favored-Nation” pricing for pharmaceutical products.
+Added: If implemented, a “Most-Favored-Nation” pricing policy that is determined to apply to us and any of our products that receives regulatory approval based on a reference to the lowest ex-U.S.
+Added: list price for such products, could significantly reduce the U.S.
+Added: list price for such products and likewise reduce our annual market opportunity in the United States.
Our business could be negatively impacted by environmental, social and corporate governance (ESG) matters or our reporting of such matters.*
There is an increasing focus from certain investors, employees, partners, and other stakeholders concerning ESG matters, and in many cases with conflicting views.
−Removed: While we have had internal efforts directed at ESG matters, we may be perceived by certain stakeholders as not acting responsibly in connection with these matters, which could negatively impact us.
+Added: While we have had internal efforts directed at ESG matters, we may be
+Added: perceived by certain stakeholders as not acting responsibly in connection with these matters, which could negatively impact us.
The SEC recently adopted rules designed to enhance and standardize climate-related disclosures, which were stayed pending judicial review, and the SEC subsequently voted to cease its defense of the climate-related disclosure rules, effectively halting their implementation.
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Any disclosure to or misappropriation by third parties of our confidential proprietary information could enable competitors to quickly duplicate or surpass our technological achievements, thus eroding our competitive position in our market.
−Removed: Under the Servier Agreement, we have an exclusive license to develop and commercialize certain anti-CD19 allogeneic CAR T cell product candidates, including cema-cel, and we hold the commercial rights to these product candidates in the United States, the European Union and the United Kingdom.
+Added: Under the Servier Agreement, we have an exclusive license to develop and commercialize certain anti-CD19 allogeneic CAR T cell product candidates, including cema-cel, and we hold the commercial rights to these product candidates
+Added: in the United States, the European Union and the United Kingdom.
We also have an exclusive worldwide license from Cellectis to its TALEN gene-editing technology for the development of allogeneic T cell product candidates directed against 15 different cancer antigens.
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Furthermore, even if they are unchallenged, our patents and patent applications may not adequately protect our intellectual property or prevent others from designing their products to avoid being covered by our claims.
−Removed: If the breadth or strength of protection provided by the patents and patent applications we hold with respect to our product candidates is
−Removed: threatened, it could dissuade companies from collaborating with us to develop, and threaten our ability to commercialize, our product candidates.
+Added: If the breadth or strength of protection provided by the patents and patent applications we hold with respect to our product candidates is threatened, it could dissuade companies from collaborating with us to develop, and threaten our ability to commercialize, our product candidates.
Further, if we encounter delays in our clinical trials, the period of time during which we could market our product candidates under patent protection would be reduced.
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Confidentiality agreements with employees and third parties, including any strategic partners, may not prevent unauthorized disclosure or use of trade secrets and other proprietary information.
−Removed: 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.
+Added: 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
+Added: technology that is not covered by patents.
Trade secrets, however, may be difficult to protect.
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As part of the lawsuit, Roche seeks to obtain ownership of certain Stanford patents covering the PhasED-Seq technology that are licensed to Foresight Diagnostics.
−Removed: Foresight Diagnostics has stated that it believes that Roche’s allegations are meritless and that it intends to vigorously defend against the case, and in October 2024 Foresight Diagnostics and Stanford filed motions seeking to have the lawsuits dismissed.
−Removed: If 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
−Removed: commercialize cema-cel as part of a 1L consolidation strategy, if approved, which could materially adversely affect our business, operating results and financial condition.
+Added: Foresight Diagnostics has stated that it believes that Roche’s allegations are meritless and that it intends to vigorously defend against the case.
+Added: In August 2025, the parties filed a joint stipulation indicating that Roche and Foresight have entered into a term sheet to resolve the litigation for all parties.
+Added: The term sheet obligates the parties to negotiate and finalize a definitive settlement agreement by August 29, 2025.
+Added: The parties have asked the Court to stay the litigation pending final resolution.
+Added: If 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.
In addition, we are aware of several U.S.
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If any third-party patents were held by a court of competent jurisdiction to cover the manufacturing process of our product candidates, constructs or molecules used in or formed during the manufacturing process, or any final product itself, the holders of any such patents may be able to block our ability to commercialize the product candidate unless we obtained a license under the applicable patents, or until such patents expire or they are finally determined to be held not infringed, unpatentable, invalid or unenforceable.
−Removed: 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.
+Added: 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
+Added: determined to be held not infringed, unpatentable, invalid or unenforceable.
In either case, such a license may not be available on commercially reasonable terms or at all.
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The licensing and acquisition of third-party intellectual property rights is a competitive area, and companies, which may be more established, or have greater resources than we do, may also be pursuing strategies to license or acquire third-party intellectual property rights that we may consider necessary or attractive in order to commercialize our product candidates.
−Removed: established companies may have a competitive advantage over us due to their size, cash resources and greater clinical development and commercialization capabilities.
+Added: More established companies may have a competitive advantage over us due to their size, cash resources and greater clinical development and commercialization capabilities.
We may be involved in lawsuits to protect or enforce our patents or the patents of our licensors, which could be expensive, time-consuming and unsuccessful.
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Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions.
−Removed: The legal systems of certain countries, particularly certain developing countries where Overland
−Removed: Therapeutics or its affiliates may do business, do not favor the enforcement of patents, trade secrets and other intellectual property protection, particularly those relating to biopharmaceutical products, which could make it difficult for us or Overland Therapeutics or any of its affiliates to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally.
+Added: The legal systems of certain countries, particularly certain developing countries where Overland Therapeutics or its affiliates may do business, do not favor the enforcement of patents, trade secrets and other intellectual property protection, particularly those relating to biopharmaceutical products, which could make it difficult for us or Overland Therapeutics or any of its affiliates to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally.
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.
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If any of the analysts who cover us issue an adverse or misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if the clinical trials and operating results fail to meet the expectations of analysts, our stock price would likely decline.
−Removed: If one or more analysts cease coverage of us or fail to
−Removed: publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.
+Added: If one or more analysts cease coverage of us or fail to publish reports on us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.
Unregistered Sales of Equity Securities and Use of Proceeds.
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.