9 unchanged sentences
Risks Relating to Our Financial Position and Need for Additional Capital
−Removed: We have incurred significant net losses since our inception and anticipate that we will incur continued net losses for the foreseeable future.
−Removed: We have incurred significant net losses each year since our inception.
+Added: We have incurred significant operating losses since our inception and anticipate that we will incur continued operating losses for the foreseeable future and we may not be able to achieve or sustain profitability.
+Added: We have incurred significant operating losses each year since our inception.
For the years ended December 31, 2023 and 2022, we incurred net losses of $102.1 million and $99.4 million, respectively.
2 unchanged sentences
We have devoted almost all of our financial resources to research and development, including our preclinical development activities.
−Removed: We expect to continue to incur significant expenses and net losses over the next several years and for the foreseeable future as we seek to advance product candidates through preclinical and clinical development, expand our research and development activities, develop new product candidates, complete preclinical studies and clinical trials, seek regulatory approval and, if we receive approval from the FDA or foreign regulatory authorities, commercialize our products.
+Added: We expect to continue to incur significant expenses and operating losses over the next several years and for the foreseeable future as we seek to advance product candidates through preclinical and clinical development, expand our research and development activities, develop new product candidates, complete preclinical studies and clinical trials, seek regulatory approval and, if we receive approval from the FDA or foreign regulatory authorities, commercialize our products.
Furthermore, the costs of advancing product candidates into each succeeding clinical phase tend to increase substantially over time.
2 unchanged sentences
We anticipate that our expenses will increase substantially if and as we:
−Removed: • progress our ANTLER phase 1 clinical trial for our CB-010 product candidate and our CaMMouflage phase 1 clinical trial for our CB-011 product candidate;
−Removed: • continue our current research programs and our preclinical and clinical development of our other current product candidates, including CB-012 and CB-020, and any other product candidates we identify and choose to develop;
+Added: • progress our clinical trials for our CAR-T product candidates;
+Added: • continue our current research programs and our preclinical and clinical development of our other current product candidates and any other product candidates we identify and choose to develop;
• hire additional clinical, quality control, regulatory, and scientific personnel;
6 unchanged sentences
• add operational, legal, financial, and management information systems and personnel;
−Removed: • experience any delays, challenges or other issues associated with any of the above, including the failure of clinical trials meeting endpoints, the generation of unanticipated preclinical study results or clinical trial data
−Removed: Table of Conte n t s
−Removed: subject to differing interpretations, or the occurrence of potential safety issues or other development or regulatory challenges;
+Added: • experience any delays, challenges or other issues associated with any of the above, including the failure of clinical trials meeting endpoints, the generation of unanticipated preclinical study results or clinical trial data subject to differing interpretations, or the occurrence of potential safety issues or other development or regulatory challenges;
• make royalty, milestone, or other payments under current, and any future, in-license or assignment agreements;
13 unchanged sentences
Because our allogeneic cell therapy product candidates are based on new technologies, they require extensive research and development and have substantial manufacturing costs.
−Removed: In addition, clinical costs to treat cancer patients with our product candidates, including treatment of any potential side effects that may arise, will be significant.
+Added: In addition, clinical costs to treat patients with our product candidates, including treatment of any potential side effects that may arise, will be significant.
As of December 31, 2023, we had cash, cash equivalents, and marketable securities of $372.4 million.
3 unchanged sentences
• costs, progress, and results of our product candidate preclinical studies and clinical trials;
−Removed: • potential delays in our preclinical studies and clinical trials, whether current or planned, due to unforeseen events as well as other factors such as the economic environment or the COVID-19 pandemic or other public health crises;
+Added: • potential delays in our preclinical studies and clinical trials, whether current or planned, due to unforeseen events as well as other factors such as the economic environment or pandemics or other public health crises;
+Added: • potential difficulties and delays in receiving regulatory clearances and/or approvals for our product candidates;
• costs and prioritization of our research and development programs as well as costs to acquire or in-license technologies or other product candidates;
2 unchanged sentences
• timing and outcome of regulatory review of our product candidates;
−Removed: Table of Conte n t s
−Removed: • success of our collaboration with AbbVie and our receipt of reimbursements due thereunder;
−Removed: • our ability to establish and maintain additional collaborations on favorable terms;
+Added: • our ability to establish and maintain collaborations on favorable terms;
• costs of fulfilling our contractual obligations to reimburse certain parties for costs incurred in connection with the prosecution and maintenance of licensed patent rights, including reimbursements owed to The Regents of the University of California;
17 unchanged sentences
To the extent that we raise additional capital through the sale of equity or convertible debt securities, our stockholders’ interests will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our common stockholders.
+Added: Attempting to secure additional financing may also divert our management from our day-to-day activities, which could impair or delay our ability to develop our product candidates.
+Added: Furthermore, if, in the future, one or more banks or financial institutions enter receivership or become insolvent in response to financial conditions affecting the banking system or financial markets, our ability to access our existing cash, cash equivalents, and marketable securities may be threatened and could have a material impact on our business and financial condition.
If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce, or terminate our product development or future commercialization efforts.
−Removed: Alternatively, we could be required to seek collaborators for our product candidates at an earlier stage than would otherwise be desirable or on terms that are less favorable than might otherwise be available.
−Removed: We might need to relinquish or license on unfavorable terms our rights to our product candidates in markets where we otherwise would seek to pursue development and commercialization
−Removed: Table of Conte n t s
−Removed: ourselves, or to license our intellectual property to others who could develop products that will compete with our products.
+Added: Alternatively, we could be required to seek collaborators for our product candidates at an earlier stage than would otherwise be desirable or on terms
+Added: that are less favorable than might otherwise be available.
+Added: We might need to relinquish or license on unfavorable terms our rights to our product candidates in markets where we otherwise would seek to pursue development and commercialization ourselves, or to license our intellectual property to others who could develop products that will compete with our products.
Any of these actions could have a material adverse effect on our business, financial condition, results of operations, and prospects.
22 unchanged sentences
We are early in our development efforts and it will be many years before we commercialize a product candidate, if ever.
−Removed: If we are unable to advance our product candidates through clinical trials, obtain regulatory approval, and ultimately commercialize our product candidates, or experience significant delays in doing so, our business will be materially harmed.
+Added: If we are unable to advance our product candidates through clinical trials, obtain regulatory approval, and ultimately commercialize our product candidates, or we experience significant delays in doing so, our business will be materially harmed.
We are early in the development of our cell therapy product candidates and have focused our research and development efforts to date on various CRISPR genome-editing technologies, including our chRDNA genome-editing technology, as well as identifying our initial CAR-T cell product candidates.
1 unchanged sentence
Our ability to generate product revenue, which we do not expect will occur for many years, if ever, will be a result of the successful development and eventual commercialization of our product candidates, which may never occur.
−Removed: Our product candidates may have adverse side effects or fail to demonstrate safety and efficacy.
+Added: Our product candidates may have expected or unexpected adverse side effects or fail to demonstrate safety and efficacy.
Additionally, our product candidates may have other characteristics that may make them impractical or prohibitively expensive for large-scale manufacturing.
+Added: In certain cases, CROs and clinical trial sites may fail to conduct the clinical trials as planned, may fail to comply with applicable requirements, or may deviate from the clinical trial protocols.
Furthermore, our product candidates may not receive regulatory approval or, if they do, they may not be accepted by the medical community or patients or may not be competitive with other products that become available.
−Removed: We currently have no product revenue and we may never be able to successfully develop or commercialize a marketable product.
−Removed: Table of Conte n t s
+Added: currently have no product revenue and we may never be able to successfully develop or commercialize a marketable product.
We must submit IND applications to the FDA to initiate clinical trials in the United States.
−Removed: In September 2020, we announced that the FDA had cleared our IND application for our first product candidate, CB-010, and, in November 2022, we announced that the FDA had cleared our IND application for our second product candidate, CB-011.
+Added: In September 2020, we announced that the FDA had cleared our IND application for our first product candidate, CB-010, in November 2022, we announced that the FDA had cleared our IND application for our second product candidate, CB-011, and, in October 2023, we announced that the FDA had cleared our IND application for our third product candidate, CB-012.
The filing of future IND applications for our other product candidates is subject to additional preclinical research, research-scale and clinical-scale manufacturing, exploration of possible other genome-editing systems, evaluation of potential targets, and other factors yet to be identified.
3 unchanged sentences
They could impose a clinical hold, which may require us to complete additional preclinical studies or clinical trials.
+Added: The FDA and foreign regulatory authorities may refuse to clear our IND applications.
The success of our product candidates will depend on several factors, including the following:
2 unchanged sentences
• ability to develop and deploy armoring technologies so that our product candidates have a competitive edge;
−Removed: • completion of preclinical studies;
+Added: • successful completion of preclinical studies;
• clearance of IND applications to initiate clinical trials;
9 unchanged sentences
• identification and establishment of a stable supply chain that permits us to procure the necessary materials for our product candidates;
+Added: • legal and regulatory compliance by third parties that provide services to us or on our behalf, including but not limited to CMOs, suppliers, and clinical research organizations (“CROs”), some of which may be subject to regulatory investigations;
+Added: • the ability of CROs and clinical trial sites to conduct our clinical trials;
• maintenance of a continued acceptable safety profile of products post-approval;
• acceptance of product candidates, if and when approved, by patients, the medical community, and third-party payors;
−Removed: • effective competition with other therapies and treatment options;
+Added: • effective competition with other therapies and treatment options, including but not limited to autologous CAR-T cell therapies, small molecules, and antibody treatment;
• establishment and maintenance of healthcare coverage and adequate reimbursement;
• expanding indications and patient populations for our products post-approval.
−Removed: Table of Conte n t s
Our product candidates are cell therapies generated by our novel CRISPR chRDNA genome-editing technologies, which make it difficult to predict the time and cost of developing these product candidates and obtaining regulatory approval.
22 unchanged sentences
CRISPR genome editing generally is relatively new;
−Removed: to date, no genome-editing technologies have been approved in the United States although clinical trials of product candidates based on CRISPR-Cas9 and other genome-editing technologies are underway.
−Removed: As a result, the regulatory approval process for cell therapy product candidates such as ours is uncertain and may be more expensive and take longer than the approval process for product candidates based on better known or more extensively studied technologies.
+Added: to date, only one cell therapy product using CRISPR-Cas9 genome editing has been approved in the United States although clinical trials of additional product candidates based on CRISPR-Cas9 and other genome-editing technologies are underway.
+Added: As a result, the regulatory approval process for cell
+Added: therapy product candidates such as ours is uncertain and may be more expensive and take longer than the approval process for product candidates based on better known or more extensively studied technologies.
As such, it is difficult to accurately predict the developmental challenges we may face as we progress our product candidates through preclinical studies and clinical trials.
3 unchanged sentences
There can be no assurance that any development problems we experience in the future related to our chRDNA technologies or any of our research programs will not cause significant delays or unanticipated costs, or that such development problems can be solved.
−Removed: We may not achieve the desired safety and
−Removed: Table of Conte n t s
−Removed: efficacy of our product candidates.
+Added: We may not achieve the desired safety and efficacy of our product candidates.
Also, we may not sufficiently improve genome-editing specificity and our genome editing may have off-target events.
2 unchanged sentences
We may also experience delays in developing robust, reproducible, and scalable manufacturing processes and transferring those processes to CMOs, which may prevent us from completing our clinical trials or commercializing our products on a timely or profitable basis, if at all.
−Removed: Currently, we have only manufactured our CB-010 and CB-011 product candidates for clinical trials.
−Removed: In addition, since we are in the early stages of clinical development, we do not know the doses to be used in later phase 2 or pivotal trials needed to evaluate the efficacy of our product candidates, which will affect the manufacturing requirements for our product candidates.
−Removed: Finding a suitable dose, such as a maximum tolerated dose or, as applicable, a recommended phase 2 dose, for our cell therapy product candidates may delay our anticipated clinical development timelines and prolong our clinical trials.
+Added: Currently, we have only manufactured our CB-010, CB-011, and CB-012 product candidates for clinical trials.
+Added: In addition, since we are in the early stages of clinical development, we do not know the doses to be used in later phase 2 or pivotal phase 3 clinical trials necessary to evaluate the efficacy of our product candidates, which will affect the manufacturing requirements for our product candidates.
+Added: Finding a suitable dose, such as a MTD or, as applicable, a RP2D, for our cell therapy product candidates may delay our anticipated clinical development timelines and prolong our clinical trials.
Accordingly, our expectations regarding our costs of manufacturing may vary significantly as we develop our product candidates and understand these critical factors.
1 unchanged sentence
Manufacturing of our product candidates is complex and we could experience manufacturing problems during our clinical trials, which could delay or limit commercialization of our product candidates .
−Removed: The manufacturing processes used to produce our cell therapy product candidates are and will be complex, as our product candidates are new products and, to date, only our CB-010 and CB-011 product candidates have been manufactured according to cGMPs.
+Added: The manufacturing processes used to produce our cell therapy product candidates are and will be complex, as our product candidates are new products.
Several factors could cause production interruptions including facility contaminations;
1 unchanged sentence
contamination of healthy donor cells, chRDNA guides, Cas9 and Cas12a proteins, viruses, iPSC master cell banks or working cell banks;
−Removed: natural disasters, including the COVID-19 pandemic and other public health crises;
+Added: natural disasters, including pandemics and other public health crises;
labor shortages and strikes;
13 unchanged sentences
All these factors could be costly to us and otherwise harm our business, financial condition, results of operations, and prospects.
−Removed: Table of Conte n t s
Our business is highly dependent on the success of our product candidates, which will require significant additional preclinical studies and and/or human clinical trials before we can seek regulatory approval and potentially commercialize our product candidates.
1 unchanged sentence
Our business and future success depends on our ability to advance our product candidates through preclinical studies and clinical trials, obtain regulatory approval for, and successfully commercialize, our product candidates.
−Removed: The failure of our product candidates in clinical trials, or the failure of other companies’ allogeneic anti-CD19 CAR-T and allogeneic anti-BCMA CAR-T cell therapies, including for reasons due to safety, efficacy, or the durability of response, may impede our ability to develop not only CB-010 and CB-011 but our other CAR-T and CAR-NK product candidates as well, and may significantly influence physicians’ and regulatory authorities’ opinions with regard to the viability of our entire pipeline of allogeneic cell therapies.
+Added: The failure of our product candidates in clinical trials, or the failure of other companies’ allogeneic anti-CD19 CAR-T and allogeneic anti-BCMA CAR-T cell therapies, including for reasons due to safety, efficacy, or the durability of response, may impede our ability to develop not only CB-010, CB-011, and CB-012 but our other CAR-T and CAR-NK product candidates as well, and may significantly influence physicians’ and regulatory authorities’ opinions with regard to the viability of our entire pipeline of allogeneic cell therapies.
In order to submit IND applications for our other product candidates, we will need to complete many objectives, such as our preclinical research of product candidates still in discovery and advancement of cGMP conditions for our product candidates.
15 unchanged sentences
If we do not accurately evaluate the commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing, or other royalty arrangements when it would have been more advantageous for us to retain sole development and commercialization rights to that product candidate.
−Removed: If we experience delays or difficulties enrolling patients in the clinical trials for our product candidates, including our ANTLER phase 1 clinical trial for our CB-010 product candidate and our CaMMouflage phase 1 clinical trial for our CB-011 product candidate, our ability to advance our product candidates through clinical development and the regulatory process could be delayed or prevented.
+Added: If we experience delays or difficulties enrolling patients in the clinical trials for our product candidates, including our CB-010, CB-011, and CB-012 product candidates, our ability to advance our product candidates through clinical development and the regulatory process could be delayed or prevented.
The timely completion of clinical trials depends, among other things, on our ability to enroll a sufficient number of patients who remain in the trial until its conclusion.
−Removed: We may encounter delays in enrolling or be unable to enroll a sufficient number of patients to complete any of our clinical trials and, even if patients are enrolled, they may withdraw
−Removed: Table of Conte n t s
−Removed: from our clinical trials before completion.
−Removed: For both our ANTLER and our CaMMouflage phase 1 clinical trials, we have entered into contracts with clinical research organizations (“CROs”), as well as clinical trial agreements with the sites participating in our clinical trials.
+Added: We may encounter delays in enrolling or be unable to enroll a
+Added: sufficient number of patients to complete any of our clinical trials and, even if patients are enrolled, they may withdraw from our clinical trials before completion.
+Added: For our current clinical trials, we have entered into contracts with CROs, as well as clinical trial agreements with the sites participating in our clinical trials.
Patient selection and enrollment may be challenging;
−Removed: The clinical protocol for CB-010 excludes many non-Hodgkin lymphoma patients from our ANTLER phase 1 clinical trial, including patients previously treated with anti-CD19-targeted therapy or allogeneic stem cell transplantation, patients with active or chronic GvHD requiring therapy, or patients unwilling to follow extended safety monitoring.
−Removed: The clinical protocol for CB-011 excludes some multiple myeloma patients from our CaMMouflage phase 1 clinical trial, including patients with prior CAR-T cell therapy and/or BCMA-targeted therapy within the last three months.
−Removed: Our ANTLER and CaMMouflage phase 1 clinical trials, as well as any future clinical trials for our other product candidates, will compete for enrollment of patients with other clinical trials for product candidates that are in the same cell therapeutic areas with the same or similar study populations as our product candidates.
+Added: additionally, the protocols for our ongoing clinical trials specifically exclude patients with certain prior treatments as well as other conditions.
+Added: Our current and future clinical trials, will compete for enrollment of patients with other clinical trials for product candidates that are in the same cell therapeutic areas with the same or similar study populations as our product candidates.
Our clinical trials will also compete for enrollment of patients with other clinical trials for product candidates based on non-cellular modalities, such as small molecules and antibodies, that are intended for the same or similar study populations as our product candidates.
20 unchanged sentences
• patient referral practices of physicians;
−Removed: • physicians' ability to monitor patients adequately during and after treatment because of patient healthcare access issues caused by COVID-19, other pandemics, or public health crises;
−Removed: Table of Conte n t s
• proximity and availability of clinical trial sites for prospective patients;
−Removed: • interruptions, delays, or staffing shortages resulting from the COVID-19 pandemic, other pandemics, or public health crises.
+Added: • interruptions, delays, or staffing shortages resulting from pandemics or other public health crises.
Enrollment delays in our clinical trials may result in increased development costs for any product candidates we may develop, which may cause our stock price to decline and limit our ability to obtain additional financing.
−Removed: If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit, or terminate our ANTLER phase 1 clinical trial or our CaMMouflage phase 1 clinical trial or future clinical trials, and postpone or forgo seeking marketing approval, any of which would have an adverse effect on our business, financial condition, results of operations, and prospects.
+Added: If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit, or
+Added: terminate our current clinical trials, or future clinical trials, and postpone or forgo seeking marketing approval, any of which would have an adverse effect on our business, financial condition, results of operations, and prospects.
Clinical trials are expensive, time-consuming, and subject to uncertainty.
9 unchanged sentences
• failure to manufacture sufficient quantities of our product candidates for use in our clinical trials;
−Removed: • failure by third-party suppliers, CMOs, CROs, and clinical trial sites to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
+Added: • failure by CMOs, suppliers, CROs, or clinical trial sites to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;
• imposition of a temporary or permanent clinical hold by us, IRBs for the institutions at which such trials are being conducted, or by the FDA or other regulatory authorities for safety or other reasons, such as a result of a new safety finding in a clinical trial on a similar product by one of our competitors, that presents unreasonable risk to clinical trial participants;
6 unchanged sentences
• inability to establish clinical trial endpoints that applicable regulatory authorities consider clinically meaningful, or, if we seek accelerated approval, that applicable regulatory authorities consider likely to predict clinical benefit;
−Removed: Table of Conte n t s
• regulators withdrawing their approval of a product or imposing restrictions on its distribution;
−Removed: • interruptions, delays, or staffing shortages resulting from the COVID-19 pandemic, other pandemics, or public health crises.
+Added: • interruptions, delays, or staffing shortages resulting from pandemics or other public health crises.
If (i) we are required to extend the duration of any clinical trials or to conduct additional preclinical studies or clinical trials or other testing of our product candidates beyond those that we currently contemplate;
(ii) we are unable to successfully complete preclinical studies or clinical trials of our product candidates or other testing;
−Removed: (iii) the results of these trials, studies, or tests are negative or produce inconclusive results;
+Added: (iii) the results of these
+Added: trials, studies, or tests are negative or produce inconclusive results;
(iv) there are safety concerns;
8 unchanged sentences
• have regulatory agencies remove the product from the market or we voluntarily withdraw the product from the market after obtaining marketing approval.
−Removed: Our clinical trials may fail to adequately demonstrate the safety and efficacy of any of our product candidates and the development of our product candidates may be delayed or unsuccessful, which could prevent or delay regulatory approval and commercialization.
+Added: Our clinical trials may fail to adequately demonstrate the safety and efficacy of any of our product candidates and, if this happens, the development of our product candidates may be delayed or unsuccessful, which could prevent or delay regulatory approval and commercialization.
Our product candidates are in various stages of preclinical and clinical development.
12 unchanged sentences
These data also remain subject to audit and verification procedures that may result in the final data being materially different from the data we previously published.
−Removed: The information that we choose to
−Removed: Table of Conte n t s
−Removed: disclose publicly regarding preclinical studies or clinical trials is typically a summary of extensive information, and others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities, or otherwise regarding a particular product candidate or our product candidates generally.
+Added: The information that we choose to disclose publicly regarding preclinical studies or clinical trials is typically a summary of extensive information, and others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities, or otherwise regarding a particular product candidate or our product candidates generally.
As a result, initial, interim, and preliminary data should be viewed with caution until the final data are available.
4 unchanged sentences
If we are unable to advance our product candidates through clinical trials to seek marketing approval, our business, financial condition, results of operations, and prospects will be materially harmed.
−Removed: If our product candidates cause serious adverse events or undesirable side effects, including injury and death, or have other properties that could delay or prevent regulatory approval, their commercial potential may be limited or extinguished.
+Added: If our product candidates cause serious adverse events or undesirable side effects, including injury and death, or have other properties that could delay or prevent regulatory approval, they would have limited or no commercial potential.
Product candidates we develop may be associated with undesirable or unacceptable side effects, unexpected characteristics, or other SAEs, including death.
Immunotherapy, and its method of action of harnessing the immune system, is powerful and could lead to serious side effects that we only discover in clinical trials.
−Removed: In addition to potential SAEs from the immune system or side effects caused by our CB-010 or our CB-011 product candidate, or any product candidate we may develop and advance into one or more clinical trials, the product candidate administration process and related procedures may also cause undesirable side effects.
−Removed: Patients who enroll in our ANTLER phase 1 clinical trial or our CaMMouflage phase 1 clinical trial undergo a lymphodepletion regimen, including administration of fludarabine and cyclophosphamide, which can lead to SAEs.
+Added: In addition to potential SAEs from the immune system or side effects caused by our product candidates currently in clinical trials, or any product candidate we may develop and advance into one or more clinical trials, the product candidate administration process and related procedures may also cause undesirable side effects.
+Added: Patients who enroll in our current clinical trial undergo a lymphodepletion regimen, including administration of fludarabine and cyclophosphamide, which can lead to SAEs.
Because these regimens will cause a transient and sometimes prolonged blood count suppression, patients have an increased risk of leukopenia, anemia, thrombocytopenia bleeding, or infection, which could ultimately lead to death.
7 unchanged sentences
The FDA or other regulatory agencies may disagree with our regulatory plans and we may fail to obtain regulatory approval of our cell therapy product candidates.
−Removed: If and when our ANTLER phase 1 clinical trial for our CB-010 product candidate is completed and, assuming positive data, we will propose to advance to a pivotal clinical trial, and will propose the same for our CB-011 product candidate when our CaMMouflage phase 1 clinical trial is completed.
+Added: If and when each of our phase 1 clinical trials for our CAR-T product candidates is completed and, assuming positive data, we will propose to the FDA that such product candidate advance to a pivotal phase 3 clinical trial.
Although the FDA has found substantial evidence to support approval outside of the traditional phase 1, phase 2, and phase 3 framework for the approved autologous anti-CD19 and anti-BCMA CAR-T cell therapies, the general approach for FDA approval of a new biologic is for the sponsor to provide dispositive data from at least two adequate and well-controlled clinical trials of the relevant biologic in the applicable patient population.
1 unchanged sentence
We do not have agreement or guidance from the FDA that our regulatory development plans will be sufficient for submission of a BLA.
−Removed: For example, the FDA may require that we conduct a comparative trial against an approved therapy, such as an approved autologous CAR-T cell therapy, which would significantly delay our development
−Removed: Table of Conte n t s
−Removed: timelines and require substantially more resources.
+Added: For example, the FDA may require that we conduct a comparative trial against an approved therapy, such as an approved autologous CAR-T cell therapy, which would significantly delay our development timelines and require substantially more resources.
In addition, the FDA may limit our evaluation to patients who have failed or who are ineligible for autologous therapy, patients who may be difficult to treat, or patients with advanced and aggressive cancer, and our product candidates may fail to improve outcomes for those patients.
7 unchanged sentences
• we may be unable to demonstrate that the clinical and other benefits of our product candidates outweigh the safety risks;
−Removed: • the data collected from clinical trials of our product candidates may not be sufficient to the satisfaction of the FDA or other regulatory authorities to support the submission of a BLA or a similar filing in a foreign jurisdiction or to support commercial reimbursement;
+Added: • the data collected from clinical trials of our product candidates may not be sufficient to the satisfaction of the FDA or other regulatory authorities to support the submission of a BLA or a similar filing in a foreign jurisdiction or to support commercial reimbursement or reimbursement under publicly-funded health systems;
+Added: • new information or data indicating safety concerns with CAR-T cell therapies may result in the FDA or other regulatory authorities declining to approve or requiring additional clinical data for our product candidates;
• the FDA or other authorities will review our manufacturing processes and inspect our CMOs’ facilities and may not approve our manufacturing processes or CMOs’ facilities;
12 unchanged sentences
We have not previously submitted a BLA to the FDA or made a similar submission to any foreign regulatory authority.
−Removed: A BLA must include extensive preclinical and clinical data and supporting information to establish our product candidate’s safety and efficacy
−Removed: Table of Conte n t s
−Removed: for each desired indication.
+Added: A BLA must include extensive preclinical and clinical data and supporting information to establish our product candidate’s safety and efficacy for each desired indication.
The BLA must also include significant information regarding the chemistry, manufacturing, and controls for our product.
3 unchanged sentences
The FDA and other regulatory authorities have substantial discretion in the approval process and may refuse to accept our BLA applications and decide that our data are insufficient and require additional preclinical studies or clinical trials.
−Removed: The same may happen with review of our product candidates by foreign regulatory authorities.
+Added: The same may happen with review of our product
+Added: candidates by foreign regulatory authorities.
In addition, varying interpretations of the data obtained from preclinical studies and clinical trials could delay, limit, or prevent marketing approval of our product candidates.
2 unchanged sentences
We expect the innovative nature of our product candidates to create further challenges in obtaining regulatory approval.
−Removed: For example, the FDA has limited experience with the development of allogeneic T cell and NK cell therapies for cancer.
+Added: For example, the FDA has limited experience with the development of allogeneic T cell and NK cell therapies for cancer and other diseases.
We may also request regulatory approval of future CAR-T or CAR-NK cell therapy product candidates by target, regardless of cancer type or origin, which the FDA may have difficulty accepting if our clinical trials have only involved cancers of certain types or origins.
18 unchanged sentences
The FDA granted RMAT designation for our CB-010 product candidate for r/r LBCL as well as fast track designation for r/r B-NHL.
+Added: The FDA granted fast track designation for our CB-011 product candidate in r/r MM.
Although obtaining each of these designations has specific and different criteria, they are reserved for therapeutic products that are intended for serious diseases, and each designation offers certain benefits to prioritize the review and approval of such therapeutic option, which may include rolling reviews, intensive guidance, or approval based on surrogate endpoint or an intermediate clinical endpoint that is reasonably likely to predict a drug’s clinical benefit.
However, there is no assurance that we will be able to obtain such designations in the future and, even with expedited designation, we may ultimately fail to obtain FDA’s full approval for our product candidates, or the approved indication may be narrower than the indication covered by the designation.
−Removed: Table of Conte n t s
−Removed: We may continue to seek orphan drug designation for our allogeneic CAR-T and CAR-NK cell therapy product candidates across various indications, but we may not be able to obtain such designations or to maintain the benefits associated with orphan drug designation, including market exclusivity, which may cause our revenue, if any, to be reduced.
+Added: We may continue to seek orphan drug designation for our allogeneic CAR-T and CAR-NK cell therapy product candidates across various indications, but we may not be able to obtain such designations or to maintain the benefits
+Added: associated with orphan drug designation, including market exclusivity, which may cause our revenue, if any, to be reduced.
We may submit applications to FDA for additional orphan drug designation for our allogeneic CAR-T and CAR-NK cell therapy product candidates in specific orphan indications in which there is a medically plausible basis for the use of these products.
Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is intended to treat a rare disease or condition, defined as a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.
−Removed: Although we received orphan drug designation from the FDA for our CB-010 product candidate in follicular lymphoma, there is no guarantee that we will obtain additional designations for other indications or for our other product candidates as the FDA may decline future requests if it determines that our product candidates and the proposed indications do not meet the threshold for the orphan drug designation.
+Added: Although we received orphan drug designation from the FDA for our CB-010 product candidate in FL and for our CB-011 product candidate in the treatment of MM, there is no guarantee that we will obtain additional designations for other indications or for our other product candidates as the FDA may decline future requests if it determines that our product candidates and the proposed indications do not meet the threshold for the orphan drug designation.
Even if we obtain additional orphan drug designations, we may not be the first company to obtain FDA approval for the orphan drug indication, in which case exclusive marketing rights would not be available to us.
14 unchanged sentences
Even if we receive marketing approval for a product candidate, the approval may be subject to limitations on the indicated uses for which the product may be marketed or to the conditions of approval or contain requirements for costly post-marketing testing and studies to further assess the safety or efficacy of the product.
−Removed: The FDA also may place other conditions on our approval, including the requirement for a REMS to ensure the safe use of the product by reinforcing
−Removed: Table of Conte n t s
−Removed: medication use behaviors and actions.
+Added: The FDA also may place other conditions on our approval, including the requirement for a REMS to ensure the safe use of the product by reinforcing medication use behaviors and actions.
If the FDA concludes a REMS is needed, we must submit a proposed REMS before our product candidate will be eligible to receive marketing approval.
−Removed: A REMS could include medication guides, physician communication plans, or other elements to ensure safe use, such as restricted distribution methods, patient registries, and other risk minimization tools.
+Added: A REMS could include medication guides, physician communication plans, or other elements to ensure safe use, such as restricted distribution methods, patient registries, and
+Added: other risk minimization tools.
Certain REMS programs can significantly impact and restrict the marketability of our products, even if our products are approved.
23 unchanged sentences
Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate negative publicity and adversely affect our reputation.
−Removed: The occurrence of any
−Removed: Table of Conte n t s
−Removed: event or penalty described above may inhibit our ability to commercialize any product candidates we develop and adversely affect our business, financial condition, results of operations, and prospects.
+Added: The occurrence of any event or penalty described above may inhibit our ability to commercialize any product candidates we develop and adversely affect our business, financial condition, results of operations, and prospects.
We may never obtain approval to commercialize our product candidates outside the United States, which could limit our ability to recognize the full market potential of our product candidates and could materially impair our ability to generate revenues.
12 unchanged sentences
Since the regulatory framework in the United Kingdom covering pharmaceutical products is derived from EU directives and regulations, Brexit could materially impact the future regulatory requirements for product candidates and products in the United Kingdom as there is now potential for the UK regulations to diverge from the EU regulations.
−Removed: In the meantime, the Medicines and Healthcare products Regulatory Agency (the “MHRA”), the medicines and medical devices regulator in the United Kingdom, has published detailed guidance for industry and organizations to follow as of January 1, 2021, which is updated as necessary.
+Added: In the meantime, the Medicines and Healthcare products Regulatory Agency (“MHRA”), the medicines and medical devices regulator in the United Kingdom, has published detailed guidance for industry and organizations to follow as of January 1, 2021, which is updated as necessary.
A number of new marketing authorization routes have been introduced post-Brexit under the UK Human Medicines Regulations 2012 (SI 2012/1916) to allow for quick recognition of products that are approved in the EU and to allow greater flexibility in the UK procedures (such as a “rolling review” that permits the submission of an application in modules).
+Added: As of January 1, 2024, the MHRA is applying its new International Reliance Procedure to medicines approved in other jurisdictions (including by the FDA and EMA) that meet certain criteria to undergo a fast-tracked MHRA review to obtain and/or update a marketing authorization in the UK.
Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, may force us to restrict or delay efforts to seek regulatory approval in the United Kingdom for our product candidates, which could harm our business.
9 unchanged sentences
This is the gene in which a mutation occurs in patients with the inherited blood disorder beta thalassemia.
−Removed: Although this research was purposefully conducted in embryos that were not viable, the work prompted calls for a moratorium or other types of
−Removed: Table of Conte n t s
−Removed: restrictions on genome editing of human eggs, sperm, and embryos.
−Removed: Additionally, in November 2018, a researcher at the Southern University of Science and Technology in Shenzhen, China, reportedly claimed they had created the first human genome-edited babies, which was subsequently confirmed by Chinese authorities and was negatively received by the public, in particular by those in the scientific community.
+Added: Although this research was purposefully conducted in embryos that were not viable, the work prompted calls for a moratorium or other types of restrictions on genome editing of human eggs, sperm, and embryos.
+Added: Additionally, in November 2018, a researcher at the
+Added: Southern University of Science and Technology in Shenzhen, China, reportedly claimed they had created the first human genome-edited babies, which was subsequently confirmed by Chinese authorities and was negatively received by the public, in particular by those in the scientific community.
In the wake of the claim, the World Health Organization established a new advisory committee to create global governance and oversight standards for human genome editing.
19 unchanged sentences
If we are unable or decide not to establish internal sales, marketing, and distribution capabilities, we will need to enter into arrangements with third parties to perform sales, marketing, and distribution services.
−Removed: In such cases, our product revenue or the profitability to us from these revenue streams is likely to be lower than if we were to market and sell any
−Removed: Table of Conte n t s
−Removed: product candidates that we develop ourselves.
+Added: In such cases, our product revenue or the profitability to us from these revenue streams is likely to be lower than if we were to market and sell any product candidates that we develop ourselves.
In addition, we may not be successful in entering into arrangements with third parties to sell and market our product candidates or may be unable to do so on terms that are favorable to us.
−Removed: We likely will have little control over those third parties and they may fail to devote the necessary resources and attention to sell and market our product candidates effectively.
+Added: likely will have little control over those third parties and they may fail to devote the necessary resources and attention to sell and market our product candidates effectively.
If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we may not be successful in commercializing our product candidates, and our business, financial condition, results of operations, and prospects will be materially adversely affected.
−Removed: Our products may not gain market acceptance among physicians, patients, hospitals, cancer treatment centers, and others in the medical community.
+Added: Our products may not gain market acceptance among physicians, patients, hospitals, cancer treatment centers, and others in the medical community, which could significantly harm our business, financial condition, results of operations, and prospects.
The use of CAR-T and CAR-NK cells as potential cancer treatments is a recent development and may not become broadly accepted by physicians, patients, hospitals, cancer treatment centers, and others in the medical community.
16 unchanged sentences
• the effectiveness of our sales and marketing efforts;
+Added: • potential product liability claims.
If our product candidates are approved but fail to achieve market acceptance among physicians, patients, hospitals, cancer treatment centers, or others in the medical community, we will not be able to generate significant revenue.
1 unchanged sentence
The market opportunities for our product candidates may be smaller than we currently believe and limited to those patients who are ineligible for or have failed prior treatment, which may adversely affect our business.
−Removed: Table of Conte n t s
target patient populations of our product candidates are small, we must be able to successfully identify patients and capture a significant market share to achieve profitability and growth.
3 unchanged sentences
Additionally, the potentially addressable patient population for our product candidates may be limited or may not be amenable to treatment with our product candidates.
−Removed: Given the small number of patients who have the eligibility criteria and diseases that we are targeting, it is critical to our ability to become profitable that we successfully identify such patients.
+Added: Given the small number of patients who have the eligibility criteria and diseases that we are or will be targeting, it is critical to our ability to become profitable that we successfully identify such patients.
The effort to identify patients with diseases we seek to treat is in early stages, and we cannot accurately predict the number of patients for whom treatment might be possible.
9 unchanged sentences
Pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if any product candidates we may develop obtain marketing approval.
−Removed: Because our product candidates represent new approaches to the treatment of cancer, we cannot accurately estimate the potential revenue from our product candidates.
+Added: Because our current product candidates represent new approaches to the treatment of cancer, we cannot accurately estimate the potential revenue from our product candidates.
Significant uncertainty exists as to the coverage and reimbursement status of any of our products for which we obtain regulatory approval.
11 unchanged sentences
The implementation of cost containment measures that third-party payors and healthcare providers are instituting and any other healthcare reforms may prevent us from being able to generate, or may reduce, our revenues from the sale of our product candidates, if approved, and our product candidates may not be profitable.
−Removed: Such reforms could have an adverse effect on anticipated revenue from product candidates for which we may obtain regulatory approval and may affect our overall
−Removed: Table of Conte n t s
−Removed: financial condition and ability to develop product candidates.
−Removed: Even if our product candidates are successful in clinical trials and receive marketing approval, we cannot provide any assurances that we will be able to obtain and maintain third-party payor coverage or adequate reimbursement for our product candidates in whole or in part.
+Added: Such reforms could have an adverse effect on anticipated revenue from product candidates for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop product candidates.
+Added: Even if our product candidates are successful in clinical trials
+Added: and receive marketing approval, we cannot provide any assurances that we will be able to obtain and maintain third-party payor coverage or adequate reimbursement for our product candidates in whole or in part.
Enacted and future healthcare legislation may increase the difficulty and cost for us to obtain approval of and commercialize our product candidates and could adversely affect our business.
24 unchanged sentences
The key competitive factors affecting the success of our product candidates are likely to be their efficacy, safety, and availability of reimbursement.
−Removed: Table of Conte n t s
Our focus is on the development of cell therapies using our chRDNA genome-editing technology.
−Removed: We are aware of several companies focused on developing therapies for various indications using CRISPR-Cas9 genome-editing technology including CRISPR Therapeutics AG, Editas Medicine, Inc., and Intellia.
+Added: We are aware of several companies focused on developing therapies for various indications using CRISPR-Cas9 and/or CRISPR-Cas12a genome-editing technology including CRISPR Therapeutics AG, Editas Medicine, Inc., and Intellia.
In addition, several academic groups have developed new genome-editing technologies based on CRISPR-Cas9, such as base editing and prime editing, as well as alternative CRISPR systems, which may have utility in therapeutic development.
3 unchanged sentences
There are also companies developing therapies using non-CRISPR genome-editing technologies, such as transcription activator-like effector nucleases, meganucleases, and zinc finger nucleases.
−Removed: These companies include bluebird bio, Inc., Allogene Therapeutics, Inc., Cellectis S.A., Precision BioSciences, Inc., and Sangamo Therapeutics.
+Added: These companies include Allogene Therapeutics, Inc., Cellectis S.A., Precision BioSciences, Inc., and Sangamo Therapeutics.
In addition to competition from other genome-edited therapies or gene or cell therapies, any product we may develop may also face competition from other types of therapies, such as small molecule, antibody, or protein therapies.
−Removed: Our allogeneic CAR-T and CAR-NK cell therapy product candidates face significant competition from multiple companies, including Allogene Therapeutics, Inc., Atara Biotherapeutics, Inc., Cellectis S.A., Celyad Oncology SA, CRISPR Therapeutics AG, Fate Therapeutics, Inc., Poseida Therapeutics, Inc., Precision BioSciences, and Sangamo Therapeutics.
+Added: Our allogeneic CAR-T and CAR-NK cell therapy product candidates face significant competition from multiple companies, including Allogene Therapeutics, Inc., Adicet Bio, Inc., Atara Biotherapeutics, Inc., Cellectis S.A., Celyad Oncology SA, CRISPR Therapeutics AG, Fate Therapeutics, Inc., Imugene Limited, Legend Biotech Corporation, Poseida Therapeutics, Inc., Precision BioSciences, and Sangamo Therapeutics.
There are over 170 preclinical- and clinical-stage autologous and allogeneic anti-CD19 CAR-T programs, some of which will be competitive with our CB-010 product candidate, and over 60 preclinical- and clinical-stage autologous and allogeneic anti-BCMA CAR-T programs, some of which will be competitive with our CB-011 product candidate.
29 unchanged sentences
and the curtailment or restructuring of our operations.
−Removed: If any of the physicians or other providers or entities with whom we expect to do business are found to not be in compliance with applicable laws, they may be subject to
−Removed: Table of Conte n t s
−Removed: criminal, civil, or administrative sanctions, including exclusions from government-funded healthcare programs and imprisonment, which could affect our ability to operate our business.
+Added: If any of the physicians or other providers or
+Added: entities with whom we expect to do business are found to not be in compliance with applicable laws, they may be subject to criminal, civil, or administrative sanctions, including exclusions from government-funded healthcare programs and imprisonment, which could affect our ability to operate our business.
Furthermore, defending against any these actions can be costly, time-consuming, and may require significant personnel resources.
2 unchanged sentences
export control licensing requirements, as well as other U.S.
−Removed: and foreign trade regulations, sanctions laws, anti-corruption laws, and anti-money laundering laws and regulations including the Foreign Corrupt Practices Act.
+Added: and foreign trade regulations, sanctions laws, anti-corruption laws, and anti-money laundering laws and regulations including the Foreign Corrupt Practices Act, which could expose us to penalties.
We develop product candidates that may be subject to U.S.
6 unchanged sentences
Anti-corruption laws are interpreted broadly.
−Removed: Our business is heavily regulated and therefore involves significant interaction with public officials, including, potentially in the future, officials of non-United States governments.
+Added: Our business is heavily regulated and therefore involves significant interaction with public officials, including, potentially in the future, officials of non-U.S.
Additionally, in many other countries, the healthcare providers who prescribe pharmaceuticals are employed by their government, and the purchasers of pharmaceuticals are government entities;
18 unchanged sentences
This could materially damage our reputation, our ability to attract and retain employees, and our business, financial condition, results of operations, and prospects.
−Removed: We face potential liability related to the privacy of health information we may obtain from the patients in our clinical trials.
+Added: We face potential liability related to the privacy of health information we may obtain from the patients in our clinical trials if we fail to comply with privacy laws.
Most healthcare providers are subject to privacy and security regulations promulgated under HIPAA, as amended by HITECH.
2 unchanged sentences
Consequently, depending on the facts and circumstances, we could face substantial criminal penalties if we knowingly receive individually identifiable health information from a HIPAA-covered healthcare provider or research institution that has not satisfied HIPAA’s requirements for disclosure of individually identifiable health information.
−Removed: In addition, if we receive sensitive personally identifiable information,
−Removed: Table of Conte n t s
−Removed: including health information, we may be subject to state laws requiring notification of affected individuals and state regulators if a breach of personal information occurs, which is a broader class of information than the health information protected by HIPAA.
+Added: In addition, if we receive sensitive personally identifiable information, including health information, we may be subject to state laws requiring notification of affected individuals and state
+Added: regulators if a breach of personal information occurs, which is a broader class of information than the health information protected by HIPAA.
We cannot assure you that we, our CROs, our clinical trial sites, and our clinical trial principal investigators with access to personally identifiable and other sensitive or confidential information relating to the patients in our clinical trials will not breach contractual obligations, or that we or they will not experience data security breaches or attempts thereof.
11 unchanged sentences
There also is the threat of consumer class actions related to these laws and the overall protection of personal data.
+Added: Additionally, the CCPA was amended by the California Privacy Rights Act (“CPRA”), which significantly amends the CCPA and imposes additional data protection obligations on covered businesses, including additional consumer rights processes, limitations on data uses, new audit requirements for higher risk data, and opt outs for certain uses of sensitive data.
+Added: It will also create a new California data protection agency authorized to issue substantive regulations, which could result in increased privacy and information security enforcement.
+Added: The majority of the provisions went into effect on January 1, 2023, and additional compliance investment and potential business process changes may be required.
+Added: Similar laws have passed in, or are being considered by, other states.
+Added: The enactment of such laws in other states could result in potentially conflicting requirements, which would make compliance challenging and costly.
+Added: The FTC and many state attorneys general continue to enforce federal and state consumer protection laws against companies for online collection, use, dissemination and security practices that appear to be unfair or deceptive.
+Added: For example, according to the FTC, failing to take appropriate steps to keep consumers’ personal information secure can constitute unfair acts or practices in or affecting commerce in violation of Section 5(a) of the Federal Trade Commission Act.
+Added: The FTC expects a company’s data security measures to be reasonable and appropriate in light of the sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and reduce vulnerabilities.
+Added: We may also be subject to new state laws governing the privacy of consumer health data, including information concerning individual health conditions and treatment.
The data privacy laws in the EU have also been significantly reformed.
−Removed: The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the GDPR.
+Added: The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the EU, including personal health data, is subject to the General Data Protection Regulation, (EU) 2016/679 (the “GDPR”).
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors.
1 unchanged sentence
In addition, the GDPR also imposes strict rules on the transfer of personal data to countries outside the EU, including the United States and, as a result, increases the scrutiny that clinical trial sites located in the European Economic Area should apply to transfers of personal data from such sites to countries that are considered to lack an adequate level of data protection, such as the United States.
−Removed: The GDPR also permits data protection authorities to require destruction of improperly gathered or used personal information or impose substantial fines for violations of the GDPR, which can be up to 4% of global revenues or €20 million, whichever is greater, and it also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.
+Added: The GDPR also permits
+Added: data protection authorities to require destruction of improperly gathered or used personal information or impose substantial fines for violations of the GDPR, which can be up to 4% of global revenues or €20 million, whichever is greater, and it also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR.
In addition, the GDPR provides that EU member states may make their own additional laws and regulations limiting the processing of personal data, including genetic, biometric, or health data.
−Removed: Furthermore, as of January 1, 2021, companies have to comply with the GDPR and also the UK GDPR, which, together with the amended UK Data Protection Act 2018, retains the GDPR in UK national law.
+Added: Furthermore, since the United Kingdom is no longer part of the EU, its data protection regulatory regime will be independent of the EU.
+Added: From January 1, 2021, companies have had to comply with the GDPR and also the United Kingdom GDPR (“UK GDPR”), which, together with the amended United Kingdom Data Protection Act 2018, retains the GDPR in UK national law.
+Added: The relationship between the United Kingdom and the EU in relation to certain aspects of data protection law remains unclear.
+Added: In addition, the longer term economic, legal, political, regulatory, and social framework to be put in place between the United Kingdom and the EU has had, and may continue to have, a material and adverse effect on global economic conditions and the stability of global financial markets and may significantly reduce global market liquidity and restrict the ability of key market participants to operate in certain financial markets.
+Added: Any of these factors could depress economic activity and restrict our access to capital, which could materially and adversely affect our business, financial condition, and results of operations.
Risks Relating to Our Intellectual Property
−Removed: If we do not possess the necessary intellectual property rights covering our CRISPR chRDNA genome-editing technologies and our product candidates, we may not be able to block competitors or to compete effectively in the market.
+Added: If we do not possess the necessary intellectual property rights covering our CRISPR chRDNA genome-editing technologies, our product candidates, and other proprietary technologies, we may not be able to block competitors or to compete effectively in the market.
Our industry is subject to rapid technological change and our success depends in large part on our ability to obtain and maintain intellectual property protection in the United States and other jurisdictions with respect to our CRISPR chRDNA platform technologies and product candidates.
−Removed: We rely upon a combination of patents, owned by us or in-
−Removed: Table of Conte n t s
−Removed: licensed from third parties, and trade secrets to protect our technology and product candidates.
+Added: We rely upon a combination of patents, owned by us or in-licensed from third parties, and trade secrets to protect our technology and product candidates.
We seek to protect our intellectual property by filing patent applications in the United States and in other jurisdictions related to our genome-editing technologies and product candidates that are important to our business.
6 unchanged sentences
and, more generally, could affect the value of our intellectual property or narrow the scope of our owned or in-licensed patents.
−Removed: With respect to both owned and in-licensed intellectual property, we cannot predict whether the patent applications we and our licensors are currently pursuing will issue as patents, whether the claims of any issued patents will provide sufficient protection, or whether, if these patents are challenged by our competitors, they will be found to be invalid, unenforceable, or not infringed.
+Added: With respect to both owned and in-licensed intellectual property, we cannot predict whether the patent applications we and our licensors are currently pursuing will grant as patents, whether the claims of any granted patents will provide sufficient protection, or whether, if these patents are challenged by our competitors, they will be found to be invalid, unenforceable, or not infringed.
The patent prosecution process is expensive, time-consuming, and complex, and we or our licensors may not be able to file, prosecute, maintain, enforce, or license all necessary or desirable patents at a reasonable cost or in a timely manner or in all jurisdictions.
It is also possible that we will fail to identify patentable aspects of our research and development in time to obtain patent protection before public disclosures are made.
−Removed: Although we may enter into non-disclosure or confidentiality agreements with parties who may have access to patentable aspects of our research and development, such as our employees, collaborators, CMOs, consultants, CROs, clinical trial site investigators and personnel, and other third parties, any one of these parties may breach their confidentiality agreements and disclose innovations before we can file a patent application, thereby jeopardizing our ability to seek patent protection.
+Added: Although we may enter into non-disclosure or confidentiality agreements with parties who may have access to patentable aspects of our research and development, such as our employees, collaborators, CMOs, suppliers, consultants, CROs, clinical trial site investigators and personnel, and other third parties, any one of these parties may breach their confidentiality agreements and disclose innovations before we can file a patent application, thereby jeopardizing our ability to seek patent protection.
The USPTO requires compliance with a number of procedural, documentary, fee payment, and other similar provisions during the patent application process.
−Removed: The ultimate outcome of our pending patent applications is uncertain and the coverage claimed in a patent application can be significantly reduced before the patent is issued.
−Removed: Even as our patent applications, or those of our licensors, currently or in the future, issue as patents, they may not issue in a form that will provide us with any meaningful protection, prevent competitors or other third parties from competing with us, dissuade companies from collaborating with us, or otherwise provide us with any competitive advantage.
−Removed: Periodic maintenance fees on issued patents are also required to be paid over the lifetime of the patent.
−Removed: Although an inadvertent lapse can, in many cases, be cured by payment of a late fee or by other means in accordance with applicable laws and regulations, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in the loss of patent rights.
+Added: The ultimate outcome of our pending patent applications is uncertain and the coverage claimed in a patent application can be significantly reduced before the patent is granted.
+Added: Even as our patent applications, or those of our licensors, currently or in the future, grant as patents, they may not grant in a form that will provide us with any meaningful protection, prevent competitors or other third parties from competing with us, dissuade companies from collaborating with us, or otherwise provide us with any competitive advantage.
+Added: Periodic maintenance fees on granted patents are also required to be paid over the lifetime of the patent.
+Added: Although an inadvertent lapse can, in many
+Added: cases, be cured by payment of a late fee or by other means in accordance with applicable laws and regulations, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in the loss of patent rights.
Noncompliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, nonpayment of fees, failure to properly legalize and submit formal documents, and the like.
10 unchanged sentences
No genome-edited products have been commercialized and there is ongoing patent litigation in the autologous CAR-T cell therapy space.
−Removed: Due to the widespread research and development that is taking place in these fields, including by us and our competitors, the
−Removed: Table of Conte n t s
−Removed: intellectual property landscape is in flux and may remain uncertain for the foreseeable future.
+Added: Due to the widespread research and development that is taking place in these fields, including by us and our competitors, the intellectual property landscape is in flux and may remain uncertain for the foreseeable future.
There may be significant litigation and administrative proceedings that could affect our genome-editing technologies and product candidates.
2 unchanged sentences
Numerous U.S.
−Removed: and foreign issued patents and pending patent applications owned by third parties exist in the fields in which we are developing our product candidates.
−Removed: As industry, government, academia, and other biotechnology and pharmaceutical research expands and more patents are issued, the risk increases that our genome-editing technologies or product candidates may give rise to claims of infringement of the patent rights of others.
+Added: and foreign granted patents and pending patent applications owned by third parties exist in the fields in which we are developing our product candidates.
+Added: As industry, government, academia, and other biotechnology and pharmaceutical research expands and more patents are granted, the risk increases that our genome-editing technologies or product candidates may give rise to claims of infringement of the patent rights of others.
We cannot guarantee that our genome-editing technologies, current and future product candidates, or the use or manufacture of such product candidates does not currently or will not in the future infringe third-party patents.
5 unchanged sentences
Numerous third-party U.S.
−Removed: and foreign issued patents and pending patent applications exist in the fields of CRISPR genome editing as well as the field of immuno-oncology, including those relating to CAR constructs and CAR-T and CAR-NK cell therapy compositions and methods of use.
−Removed: Our CB-010 product candidate, which is an allogeneic anti-CD19 CAR-T cell therapy for the treatment of r/r B-NHL, uses Cas9 chRDNAs to insert the CD19-specific CAR into the T cell genome and for an additional edit.
+Added: and foreign granted patents and pending patent applications exist in the fields of CRISPR genome editing as well as the field of immuno-oncology, including those relating to CAR constructs and CAR-T and CAR-NK cell therapy compositions and methods of use.
+Added: Our CB-010 product candidate uses Cas9 chRDNAs to insert the CD19-specific CAR into the T cell genome and for an additional edit.
Numerous parties have intellectual property relating to RNA-guided Cas9 genome editing.
−Removed: See Risk Factors - “Our ability to continue to receive licensing revenue and to enter into new licensing arrangements related to the foundational CRISPR-Cas9 intellectual property will be substantially impaired if such intellectual property is limited by administrative patent proceedings.” Our CB-011 product candidate and our CB-012 product candidate both use Cas12a chRDNAs to insert the CAR into the T cell genome and to make additional edits.
+Added: See Risk Factors - “Our ability to continue to receive licensing revenue and to enter into new licensing arrangements related to the foundational CRISPR-Cas9 intellectual property will be substantially impaired if such intellectual property is limited by administrative patent proceedings or other patent challenges,” in Item 1A of this Annual Report on Form 10-K.
+Added: Our CB-011 product candidate and our CB-012 product candidate both use Cas12a chRDNAs to insert the CAR into the T cell genome and to make additional edits.
We are aware of certain third-party patents assigned to the Broad Institute, Massachusetts Institute of Technology, and the President and Fellows of Harvard University relating to CRISPR-Cas12a genome-editing systems (Cas12a was then referred to as Cpf1), which will expire in late 2035 assuming no PTE or PTA.
Additionally, we are aware of third-party patents assigned to the U.S.
−Removed: government relating to anti-BCMA CARs as well as nucleic acids encoding such CARs, vectors comprising these nucleic acids, and host cells expressing such CARs, which will expire in 2033 assuming no PTE or PTA.
+Added: government relating to anti-BCMA CARs as well as nucleic acids encoding such CARs, vectors comprising these
+Added: nucleic acids, and host cells expressing such CARs, which will expire in 2033 assuming no PTE or PTA.
We are also aware of several third-party patents relating to various CAR compositions, methods of use, and components, including specific co-stimulatory regions.
2 unchanged sentences
patent laws, conducting clinical trials and seeking regulatory approval in the United States for therapeutic products are generally not considered an act of infringement, and similar exemptions are present in other countries.
−Removed: Nevertheless, third parties may allege that the act of filing our BLA or conducting clinical trials is outside of the safe harbor provision for activities reasonably related to the development and submission of information to the FDA for regulatory approval, and third parties may, upon our regulatory filing, assert infringement claims based on existing patents or patents that may be issued prior to our BLA filing, regardless of the merit of such claims.
+Added: Nevertheless, third parties may allege that the act of filing our BLA or conducting clinical trials is outside of the safe harbor provision for activities reasonably related to the development and submission of information to the FDA for regulatory approval, and third parties may, upon our regulatory filing, assert infringement claims based on existing patents or patents that may be granted prior to our BLA filing, regardless of the merit of such claims.
Even if we believe third-party intellectual property claims are without merit, there is no assurance that a court would find in our favor on questions of infringement, validity, enforceability, ownership, or priority.
2 unchanged sentences
patent in federal court, we would need to overcome this presumption of validity, and there can be no assurance that a court of competent jurisdiction would invalidate the patent.
−Removed: A court of competent jurisdiction could hold that these third-party patents are valid, enforceable, and infringed, which could materially and adversely affect our ability to commercialize any product candidates we may develop, including CB-010, CB-011, CB-012, and CB-020, as well as any other product candidates or technologies covered by the asserted third-party patents.
−Removed: If any third-party patents were held by a court of competent jurisdiction to cover our genome-editing technology used in the manufacturing of our product candidates or any product candidate itself or its indication, the holders of those patents may be able to block our ability to commercialize the product candidate unless and until we obtained a license
−Removed: Table of Conte n t s
−Removed: under the applicable patents, or the patents expire, or are held to be not infringed, unpatentable, invalid, or unenforceable.
+Added: A court of competent jurisdiction could hold that these third-party patents are valid, enforceable, and infringed, which could materially and adversely affect our ability to commercialize any product candidates we may develop, including CB-010, CB-011, and CB-012, as well as any other product candidates or technologies covered by the asserted third-party patents.
+Added: If any third-party patents were held by a court of competent jurisdiction to cover our genome-editing technology used in the manufacturing of our product candidates or any product candidate itself or its indication, the holders of those patents may be able to block our ability to commercialize the product candidate unless and until we obtained a license under the applicable patents, or the patents expire, or are held to be not infringed, unpatentable, invalid, or unenforceable.
We may not be able to obtain a license to the blocking patents, or the terms of the license may not be commercially viable.
27 unchanged sentences
Accordingly, we may choose not to seek patent protection in certain jurisdictions or countries, and we will not have the benefit of patent protection in such jurisdictions or countries.
−Removed: Table of Conte n t s
We may be subject to claims challenging the inventorship of our patents and other intellectual property.
6 unchanged sentences
Even if we or our licensors are successful in defending against those claims, litigation could result in substantial costs and be a distraction to our management and other employees, and the claims could have a material adverse effect on our business, financial condition, results of operations, and prospects.
−Removed: The terms of our patents may not be sufficient to effectively protect our products and business.
+Added: The terms of our patents may not be sufficient to effectively protect our products and business, and the expiration of our patents may subject us to increased competition.
Although various extensions may be available, the term of a patent, and the protection it affords, is limited.
8 unchanged sentences
A PTE cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent may be extended, and only a patent with claims covering the approved biologic, a method for its approved indication, or a method for manufacturing it may be extended.
−Removed: However, we may not be granted an extension because of, for example, failing to exercise due diligence during the clinical phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents, or otherwise failing to satisfy the applicable requirements.
+Added: However, we may not be
+Added: granted an extension because of, for example, failing to exercise due diligence during the clinical phase or regulatory review process, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents, or otherwise failing to satisfy the applicable requirements.
Moreover, we may not receive PTE or we may receive less time than we requested.
7 unchanged sentences
For small companies, such as ours, this means that we must file our patent applications earlier in our development process rather than relying on proving priority of invention and it is now easier and less costly for third parties to attack our patents, all of which could harm our business, financial condition, results of operations, and prospects.
−Removed: Table of Conte n t s
There is uncertainty regarding the patentability of certain inventions in the biotechnology and pharmaceutical areas.
3 unchanged sentences
Myriad Genetics, Inc., the Supreme Court ruled that a “naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated,” and invalidated Myriad Genetics’ claims on isolated BRCA1 and BRCA2 genes.
−Removed: To the extent that our claims relate to naturally occurring antibodies or proteins, these may be deemed to be directed to natural products or to lack an inventive concept above and beyond an isolated natural product, and a court may decide the claims are invalid under Myriad.
+Added: To the extent that our claims relate to naturally occurring antibodies or proteins, these may be deemed to be directed to natural products or to lack an inventive concept above and beyond an isolated natural product, and a court may decide the claims are invalid under the Myriad decision.
Depending on future actions by the U.S.
1 unchanged sentence
courts, the USPTO, and the relevant law-making bodies, as well as courts and patent offices in other countries, the laws and regulations governing patents could change in unpredictable ways that may weaken our ability to obtain new patents or to enforce our existing patents and patents that we might obtain in the future, which could have a material adverse effect on our existing patent portfolio and those of our licensors.
−Removed: Europe’s Unified Patent Court may present uncertainties for our ability to protect and enforce our patent rights against competitors in Europe.
−Removed: Although this new court is being implemented to provide more certainty and efficiency to patent enforcement throughout Europe, it will also provide our competitors with a new forum to use to centrally challenge our patents, rather than having to seek invalidity or non-infringement decisions on a country-by-country basis.
−Removed: It will be several years before the scope of patent rights that will be recognized by the Unified Patent Court, and the strength of patent remedies that will be provided, is known.
+Added: In Europe, a new unitary patent system took effect on June 1, 2023, which will significantly impact European patents, including those granted before the introduction of such a system.
+Added: Under the unitary patent system, European patent applications will have the option, upon grant of a patent, of becoming a Unitary Patent, which will be subject to the jurisdiction of the Unitary Patent Court (the “UPC”).
+Added: The UPC may present uncertainties for our ability to protect and enforce our patent rights against competitors in Europe.
+Added: Although this new court was implemented to provide more certainty and efficiency to patent enforcement throughout Europe, it also provides our competitors with a new forum to use to centrally challenge our patents, rather than having to seek invalidity or non-infringement decisions on a country-by-country basis.
+Added: It will be several years before the scope of patent rights that will be recognized by the UPC, and the strength of patent remedies that will be provided, is known.
We may be involved in lawsuits or other proceedings to enforce or protect our patents, the patents of our licensors, or our other intellectual property rights, which could be expensive, time-consuming, and unsuccessful.
5 unchanged sentences
In patent litigation in the United States, defendant counterclaims alleging invalidity or unenforceability are commonplace, and there are numerous grounds upon which a third party can assert invalidity or unenforceability of a patent.
−Removed: Thus, suing a third party for patent infringement puts our patents at risk and we may choose not to take such actions, thus allowing a competitor to infringe our patents.
+Added: Thus, suing a third
+Added: party for patent infringement puts our patents at risk and we may choose not to take such actions, thus allowing a competitor to infringe our patents.
Grounds for a validity challenge in a counterclaim could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness, or non-enablement.
11 unchanged sentences
Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources.
−Removed: There can be no assurance that we will have sufficient financial or other
−Removed: Table of Conte n t s
−Removed: resources for such litigation or proceedings, which may continue for several years.
+Added: There can be no assurance that we will have sufficient financial or other resources for such litigation or proceedings, which may continue for several years.
Accordingly, despite our efforts, we may not be able to prevent third parties from infringing or misappropriating or successfully challenging our intellectual property rights.
16 unchanged sentences
Additionally, we may be subject to litigation for breach of these agreements.
−Removed: Moreover, if disputes over intellectual property that we have licensed, or taken assignment of, prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize the product candidates or technologies covered by such patents, which could have a material adverse effect on our business, financial conditions, results of operations, and prospects.
+Added: Moreover, if disputes over intellectual property that we have licensed, or taken assignment of, prevent or impair our ability
+Added: to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize the product candidates or technologies covered by such patents, which could have a material adverse effect on our business, financial conditions, results of operations, and prospects.
In addition, intellectual property rights that we license in the future may include sublicenses under intellectual property owned by third parties, in some cases through multiple tiers.
6 unchanged sentences
Thus, if we do not make such payments, our licensees could be sued by Pioneer, which could result in our licensees suing us for breach of contract.
−Removed: Additionally, under the Pioneer Agreement, we licensed certain Pioneer background CRISPR-Cas9 intellectual property, particularly a patent family owned by Vilnius University and exclusively licensed to Pioneer, that we have
−Removed: Table of Conte n t s
−Removed: sublicensed to several third parties as part of our CRISPR-Cas9 out-licensing program.
+Added: Additionally, under the Pioneer Agreement, we licensed certain Pioneer background CRISPR-Cas9 intellectual property, particularly a patent family owned by Vilnius University and exclusively licensed to Pioneer, that we have sublicensed to several third parties as part of our CRISPR-Cas9 out-licensing program.
Although the Vilnius patent family does not cover our chRDNA genome-editing technologies or product candidates, if we were to materially breach the Pioneer Agreement and not cure the breach, Pioneer could terminate the Pioneer Agreement, which would expose us to possible lawsuits from a number of our sublicensees to the Vilnius University patent family.
24 unchanged sentences
We may need to cease development of a future product candidate covered by such third-party intellectual property rights.
−Removed: Table of Conte n t s
The licensing and acquisition of third-party intellectual property rights is a competitive area, and companies that 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 develop product candidates.
4 unchanged sentences
If we are unable to successfully obtain rights to required third party intellectual property rights, we may not be able to expand our product pipeline, which could have a material adverse effect on our business, financial condition, results of operations, and prospects.
−Removed: Our ability to continue to receive licensing revenue and to enter into new licensing arrangements related to the foundational CRISPR-Cas9 intellectual property will be substantially impaired if such intellectual property is limited by administrative patent proceedings.
+Added: Our ability to continue to receive licensing revenue and to enter into new licensing arrangements related to the foundational CRISPR-Cas9 intellectual property will be substantially impaired if such intellectual property is limited by administrative patent proceedings or other patent challenges.
We have an exclusive license from UC and Vienna in all fields to the CVC IP, having as inventors Drs.
15 unchanged sentences
As a result, although our license from UC/Vienna is exclusive, we do not have any rights from Dr.
−Removed: Charpentier and thus our license to the CVC IP from UC/Vienna is non-exclusive with respect to such co-owned rights.
+Added: Charpentier and thus our license to the CVC IP from UC/
+Added: Vienna is non-exclusive with respect to such co-owned rights.
Furthermore, in the United States, each co-owner is required to be joined as a party to any claim or action we may wish to bring to enforce those patent rights.
5 unchanged sentences
Specifically, the Broad Institute Inc.
−Removed: and Massachusetts Institute of Technology and, in some instances, the President and Fellows of Harvard College (individually and collectively, the “Broad”), owns a patent family (having an earliest filing date of December 12, 2012) that includes issued patents in the United States and Europe that claim certain aspects of CRISPR-Cas9 systems to edit DNA in eukaryotic (i.e., plant and animal) cells, including human cells.
+Added: and Massachusetts Institute of Technology and, in some instances, the President and Fellows of Harvard College (individually and collectively, “Broad”), owns a patent family (having an earliest filing date of December 12, 2012) that includes granted patents in the United States and Europe that claim certain aspects of CRISPR-Cas9 systems to edit DNA in eukaryotic (i.e., plant and animal) cells, including human cells.
In January 2016, the Patent Trial and Appeal Board (“PTAB”) of the USPTO declared an interference (Interference No.
1 unchanged sentence
patent applications (now U.S.
−Removed: 10,266,850) included in the CVC IP and 12 issued U.S.
+Added: 10,266,850) included in the CVC IP and 12 granted U.S.
patents owned jointly by the Broad to determine which set of inventors invented first and, thus, was entitled to patents on the invention in the United States.
The PTAB concluded at the end of the motions phase that the declared interference should be discontinued (and not progress to the priority phase) because the involved claim sets were considered patentably distinct from each other.
−Removed: Following appeal
−Removed: Table of Conte n t s
−Removed: by the CVC group, in September 2018, the U.S.
+Added: Following appeal by the CVC group, in September 2018, the U.S.
Court of Appeals for the Federal Circuit (“CAFC”), affirmed the PTAB’s decision to terminate the interference proceeding without determining which inventors actually invented the use of the CRISPR-Cas9 genome-editing technology in eukaryotic cells.
4 unchanged sentences
In February 2022, the PTAB issued its decision that the Broad inventors were the first to invent the use of CRISPR-Cas9 genome editing in eukaryotic cells;
−Removed: the owners of the CVC IP have appealed this decision to the CAFC and briefing is ongoing.
+Added: the owners of the CVC IP have appealed this decision to the CAFC.
In addition to the Broad, ToolGen, Inc., MilliporeSigma (a subsidiary of Merck KGaA), and Harvard University, each filed patent applications claiming CRISPR-Cas9-related inventions after the CVC IP was first filed (October 23, 2012 in the case of ToolGen patent family;
16 unchanged sentences
We do not know the impact of a decision by the CAFC in the appeal of the ‘115 interference on these suspended interferences.
−Removed: Opposition and appeal proceedings in the EPO are ongoing against patents owned by the Broad, ToolGen, and MilliporeSigma, and various third parties have opposed the three issued CVC European patents.
−Removed: The decision upholding the CVC European patent in amended form has been appealed within the EPO.
−Removed: Additionally, invalidation trials of the CVC IP are ongoing in Japan and China.
−Removed: Such proceedings, including appeals, are often lengthy and can lead to the revocation of a patent in its entirety, the maintenance of the patent as issued, or, depending upon the jurisdiction, the maintenance of a patent in amended form.
−Removed: These CRISPR-Cas9 patents will expire in 2033 without PTA or PTE.
+Added: Opposition and appeal proceedings in the EPO are ongoing against patents owned by the Broad, ToolGen, and MilliporeSigma as well as against the CVC IP.
+Added: Additionally, invalidation trials or appeals thereof of the CVC IP are ongoing in China, India, and Japan.
+Added: Such proceedings are often lengthy and can lead to the revocation of a patent in its entirety, the maintenance of the patent as granted, or, depending upon the jurisdiction, the maintenance of a patent in amended form.
+Added: These CVC IP will expire in 2033 without PTA or PTE.
In light of the uncertainty surrounding the CVC IP, certain third parties have negotiated royalty-stacking provisions in their sublicenses with us, whereby they can deduct from what they owe to us a certain percentage of royalties they pay to other parties with CRISPR-Cas9 patents (such as to the Broad).
−Removed: Furthermore, other third parties have adopted a “wait and see” approach and are not entering into license agreements with us or third parties until all of the uncertainty surrounding inventorship and priority among the groups with CRISPR-Cas9 patents is resolved.
+Added: Furthermore, other third parties have adopted a “wait and see” approach and are not entering into license agreements with us or third parties until all of the uncertainty
+Added: surrounding inventorship and priority among the groups with CRISPR-Cas9 patents is resolved.
If patents in the CVC IP are invalidated, certain of our sublicensees may wish to renegotiate their license agreements with us or may terminate for convenience.
5 unchanged sentences
We also enter into confidentiality and invention assignment agreements with our employees and our agreements with consultants include invention assignment obligations.
−Removed: We seek to preserve the integrity and confidentiality of our data, know-how, and trade secrets by maintaining
−Removed: Table of Conte n t s
−Removed: physical security of our premises and physical and electronic security of our information technology systems.
+Added: We seek to preserve the integrity and confidentiality of our data, know-how, and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems.
Although we have confidence in these individuals, organizations, and systems, agreements or security measures may be breached, and we may not have adequate remedies for any breaches.
11 unchanged sentences
If any of our trade secrets were to be disclosed to or independently developed by a competitor or other third party, our competitive position will be materially and adversely harmed.
−Removed: Intellectual property rights do not necessarily address all potential competitive threats.
+Added: Intellectual property rights do not necessarily address all potential competitive threats and may not adequately protect our business or permit us to maintain our competitive advantage.
The degree of future protection afforded by our intellectual property rights, whether through patents or trade secrets, is uncertain because intellectual property rights have limitations and may not adequately protect our business or permit us to maintain our competitive advantage.
9 unchanged sentences
We may not be able to protect our rights to these trademarks, which we need to build name recognition among potential partners or customers in our markets of interest.
−Removed: At times, competitors may adopt trademarks similar to ours, thereby impeding our ability to build brand identity
−Removed: Table of Conte n t s
−Removed: and possibly leading to market confusion.
+Added: At times, competitors may adopt trademarks similar to ours, thereby impeding our ability to build brand identity and possibly leading to market confusion.
In addition, there could be potential trademark infringement claims brought by owners of other registered trademarks or trademarks that incorporate variations of our unregistered trademarks.
6 unchanged sentences
thus, we must rely on third-party CMOs to manufacture clinical supplies for our product candidates.
−Removed: We currently rely on five different CMOs to supply materials to an additional CMO who manufactures the necessary CB-010 and CB-011 materials for our phase 1 clinical trials.
−Removed: We anticipate that we may need to engage other suppliers and CMOs for our clinical trials with our CB-012 and CB-020 product candidates.
−Removed: We receive the CRISPR chRDNA guides used for genome editing from one CMO, the Cas proteins (Cas9 in the case of CB-010 and Cas12a in the case of CB-011 and CB-012) from another CMO, the virus used to insert the CAR into the T cell genome from another CMO located outside the United States, and our healthy donor cells from two different sources owned by the same third-party supplier.
+Added: We currently rely on five different CMOs to supply materials to an additional CMO who manufactures the necessary CB-010, CB-011, and CB-012 product candidates for our phase 1 clinical trials.
+Added: We anticipate that we may need to engage other suppliers and CMOs for our clinical trials with our product candidates.
+Added: We receive the CRISPR chRDNA guides used for genome editing from one CMO, the Cas proteins (Cas9 in the case of CB-010 and Cas12a in the case of CB-011 and CB-012) from another CMO, the virus used to insert the CAR into the T cell genome from another CMO located outside the United States, and our healthy donor cells from multiple sources.
The virus CMO receives plasmid from another supplier used in the manufacture of the viral material.
10 unchanged sentences
In addition, we have no direct control over the ability of our CMOs and suppliers to maintain adequate quality control, quality assurance, and corresponding maintenance of records and documents, or to hire and retain trained personnel.
−Removed: If the FDA or a foreign regulatory authority inspects these third-party facilities for compliance with regulations for the manufacture and testing of materials or product candidates and, if these facilities fail inspection and cannot adequately correct deficiencies, we may need to find alternative CMOs, which would significantly impact our ability to develop and obtain regulatory approval for our product candidates, and if approved, to market our products.
−Removed: In addition, if our CMOs and suppliers are unable to timely perform or have operations temporarily halted as a result of inspection or enforcement actions taken by the FDA or other regulatory authorities, or as a result of the COVID-19 pandemic or other public health crises, we may experience manufacturing delays or delays in receiving healthy donor cells used in manufacturing our CB-010 product candidate or may need to find alternative CMOs or suppliers, which in each case would significantly impact our ability to develop, obtain regulatory approval for, and market our product candidates, if approved.
+Added: If the FDA or a foreign regulatory authority inspects these third-party facilities for compliance with regulations for the manufacture and testing of materials or product candidates and, if these
+Added: facilities fail inspection and cannot adequately correct deficiencies, we may need to find alternative CMOs, which would significantly impact our ability to develop and obtain regulatory approval for our product candidates, and if approved, to market our products.
+Added: One of our CMOs is a company with ties to China.
+Added: lawmakers have urged the U.S.
+Added: government to investigate CMOs and CROs that have ties to China to ensure that sensitive U.S.
+Added: biotechnology intellectual property is not transferred to China.
+Added: Any such investigations or other regulatory actions could affect the ability of this CMO to provide services to us in a timely manner.
+Added: In addition, if our CMOs and suppliers are unable to timely perform or have operations temporarily halted as a result of inspection or enforcement actions taken by the FDA or other regulatory authorities, or as a result of pandemics or other public health crises, we may experience manufacturing delays or delays in receiving healthy donor cells used in manufacturing our product candidates or may need to find alternative CMOs or suppliers, which in each case would significantly impact our ability to develop, obtain regulatory approval for, and market our product candidates, if approved.
We do not yet have sufficient information to reliably estimate the cost of the commercial manufacturing of our product candidates, and the actual cost to manufacture and process our product candidates could materially and adversely affect the commercial viability of our product candidates.
−Removed: Our product candidates have not been manufactured at commercial scale, may not be able to achieve commercial manufacturing, and we may be unable to create a product
−Removed: Table of Conte n t s
−Removed: inventory necessary to satisfy demands for any of our product candidates following approval.
+Added: Our product candidates have not been manufactured at commercial scale, may not be able to achieve commercial manufacturing, and we may be unable to create a product inventory necessary to satisfy demands for any of our product candidates following approval.
As a result, we may never be able to develop a commercially viable product.
9 unchanged sentences
• our CMOs may fail to adequately store the various components received from our suppliers and any damage or loss of such materials could materially impact our ability to manufacture and supply our product candidates;
+Added: • our product candidates may be damaged or otherwise made unfit for use in clinical trials during shipment from our CMOs to clinical trial sites;
• we rely on third parties to perform release tests on our product candidates prior to delivery to clinical trial sites.
3 unchanged sentences
In addition, a new CMO would have to be educated in, or develop substantially equivalent processes for, production of our product candidates;
−Removed: • as a result of the current COVID-19 pandemic or other public health crises, our CMOs and suppliers may experience production delays and shutdowns.
−Removed: Our CMO that supplies the virus we use to insert the CAR into our CB-010 CAR-T product candidate is located outside the United States.
+Added: • as a result of pandemics or other public health crises, our CMOs and suppliers may experience production delays and shutdowns.
+Added: Our CMO that supplies the virus we use to insert the CAR into our CAR-T product candidates is located outside the United States.
To date, our virus CMO has not been audited by the FDA, but it has received the cGMP certification for the manufacture of recombinant viral vectors from an EU national regulatory authority.
11 unchanged sentences
• negative consequences from changes in tax laws;
−Removed: Table of Conte n t s
• difficulties in managing international logistics and transportation;
+Added: • the CMO’s potential unfamiliarity with FDA requirements when shipping into the United States;
• workforce uncertainty in countries where labor unrest is more common than in the United States.
8 unchanged sentences
If we are unable to (i) identify and obtain donor material that satisfies specifications, (ii) agree with regulatory authorities on appropriate specifications, or (iii) address variability of donor T cells, there may be insufficient material or we may be unable to initiate or continue clinical trials on the timelines we expect, which could harm our reputation and adversely impact our business and prospects.
−Removed: Although our suppliers are currently able to provide us with donor material, if, in the future, our suppliers are unable to secure donor material due to the COVID-19 pandemic or other public health crises or for other reasons, we may no longer have sufficient donor material to manufacture our cell therapy product candidates.
+Added: Although our suppliers are currently able to provide us with donor material, if, in the future, our suppliers are unable to secure donor material due to pandemics or other public health crises or for any other reasons, we may no longer have sufficient donor material to manufacture our cell therapy product candidates.
+Added: Additionally, our donor-derived product candidates may be subject to rapid recognition by a patient’s immune system, thus limiting their potential efficacy.
We rely and will continue to rely on third parties to conduct our clinical trials.
−Removed: If these third parties do not successfully carry out their contractual duties or do not meet expected deadlines, we may not be able to obtain regulatory approval of, or commercialize, our product candidates.
−Removed: We depend, and will continue to depend, on CROs, clinical trial sites and clinical trial principal investigators, contract laboratories, and other third parties to conduct our ongoing ANTLER and CaMMouflage phase 1 clinical trials and future clinical trials.
+Added: If these third parties do not successfully carry out their contractual duties or do not meet deadlines, we may not be able to obtain regulatory approval of, or commercialize, our product candidates.
+Added: We depend, and will continue to depend, on CROs, clinical trial sites and clinical trial principal investigators, contract laboratories, and other third parties to conduct our ongoing and future clinical trials.
We will rely heavily on these third parties over the course of our clinical trials, and we control only certain aspects of their activities.
Nevertheless, we are responsible for ensuring that each of our studies is conducted in accordance with the protocol and applicable legal, regulatory, and scientific standards and regulations, and our reliance on third parties does not relieve us of our regulatory responsibilities.
−Removed: We and these third parties are required to comply with cGCPs, which are regulations and guidelines enforced by the FDA and comparable foreign regulatory authorities for the conduct of clinical trials on product candidates in clinical development.
+Added: We and these third parties are required to comply with cGCPs, which are regulations and guidelines enforced by the FDA and comparable foreign regulatory authorities for the conduct of clinical trials on product candidates
+Added: in clinical development.
Regulatory authorities enforce cGCPs through periodic inspections and for-cause inspections of clinical trial principal investigators and trial sites.
1 unchanged sentence
Moreover, our business may be implicated if any of these third parties violates federal, state, or foreign fraud and abuse or false claims laws and regulations or healthcare privacy and security laws, or provide us or government agencies with inaccurate, misleading, or incomplete data.
−Removed: Although we intend to design the clinical trials for our product candidates, our CROs will facilitate and monitor our clinical trials.
−Removed: As a result, many important aspects of our clinical development programs, including site and investigator selection, and the conduct and timing and monitoring of the study, will be partly or completely outside our direct control.
−Removed: Our reliance on third parties to conduct clinical trials will also result in less direct control over the collection, management, and quality of data developed through clinical trials than would be the case if we were relying entirely upon our own employees.
+Added: Although we design the clinical trials for our product candidates, our CROs facilitate and monitor our clinical trials.
+Added: As a result, many important aspects of our clinical development programs, including site and investigator selection, and the conduct and timing and monitoring of the study, are partly or completely outside our direct control.
+Added: Our reliance on third parties to conduct and monitor the progress of clinical trials also results in less direct control over the collection, management, and quality of data developed through clinical trials than would be the case if we were relying entirely upon our own employees.
Communicating with third parties can also be challenging, potentially leading to mistakes as well as difficulties in coordinating activities.
1 unchanged sentence
These third parties may also have relationships with other commercial entities, including our competitors, for whom they may also be conducting clinical trials or other drug development activities, which could affect their performance on our behalf.
−Removed: If these third parties do not successfully
−Removed: Table of Conte n t s
−Removed: carry out their contractual duties or obligations or meet expected deadlines, if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements, or if there are other difficulties with such third parties, such as staffing difficulties, changes in priorities, or financial distress, our clinical trials may be extended, delayed, or terminated.
+Added: If these third parties do not successfully carry out their contractual duties or obligations or meet deadlines, if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements, or if there are other difficulties with such third parties, such as staffing difficulties, changes in priorities, or financial distress, our clinical trials may be extended, delayed, or terminated.
+Added: Unauthorized access or manipulation of our clinical trial data in databases maintained or utilized by third parties may adversely affect the validity of the data from our clinical trials and, ultimately, our clinical trials.
+Added: There have been instances in the biotechnology industry of clinical trial investigators acting improperly, including data fabrication and unauthorized manipulation of data.
+Added: In addition, a growing number of cybersecurity incidents are being reported, during which certain organizations gain access to databases that contain clinical trial data and demand a ransom.
+Added: In such instances, it may be difficult to determine whether the validity of our clinical trial data has been compromised, thereby jeopardizing the entire clinical trial.
As a result, we may not be able to complete development of, obtain regulatory approval of, or successfully commercialize our product candidates.
6 unchanged sentences
Failure to do so can result in fines, adverse publicity, and civil and criminal sanctions.
−Removed: Our ANTLER phase 1 clinical trial for our CB-010 product candidate and our CaMMouflage phase 1 clinical trial for our CB-011 product candidate are posted on www.ClinicalTrials.gov.
+Added: Our ANTLER phase 1 clinical trial for our CB-010 product candidate, our CaMMouflage phase 1 clinical trial for our CB-011 product candidate, and our AMpLIFY phase 1 clinical trial for our CB-012 product candidate are posted on www.ClinicalTrials.gov.
For any violations of laws and regulations during the conduct of our preclinical studies and clinical trials, we could be subject to warning letters or enforcement action that may include civil and other penalties, up to and including criminal prosecution.
−Removed: AbbVie has the right to delay timelines or terminate our collaboration and license agreement at its sole discretion, which will affect our ability to receive reimbursements, milestone payments, and royalties.
−Removed: In addition, we may not be able to meet our obligations under the AbbVie collaboration, and the development of our product candidates may be delayed in light of our obligations to AbbVie.
−Removed: In February 2021, we entered into a multi-year collaboration and license agreement under which we will utilize our CRISPR Cas12a chRDNA genome-editing and cell therapy technologies to research and develop two new CAR-T cell therapies for AbbVie.
−Removed: We are responsible for conducting certain preclinical research, development, and manufacturing activities, including assisting in the manufacturing of all phase 1 clinical materials and assisting AbbVie with the preparation and filing of its IND applications.
−Removed: We and AbbVie develop research plans, budgets, and timelines for the two Program Slots;
−Removed: however, ultimately these are under AbbVie’s control and AbbVie may choose to delay certain activities.
−Removed: For example, the parties have agreed that all CMO manufacturing activities be performed no earlier than 2024.
−Removed: Such delays may affect the amount of reimbursement we receive and revenue we recognize from the collaboration.
−Removed: Our ability to receive significant milestone payments is based on AbbVie’s achievement of developmental, regulatory, and sales-based milestones, which is outside of our control and is dependent on AbbVie’s commercially reasonable efforts to develop, commercialize, and manufacture the licensed collaboration products.
−Removed: Any delays by AbbVie will substantially impact the timing of these milestones.
−Removed: Furthermore, AbbVie has the right to terminate the collaboration and license agreement at its sole discretion upon 90 days’ prior written notice to us, which would eliminate all future reimbursements, milestone payments, and royalties and could be perceived negatively by the market.
−Removed: The collaboration involves a number of our employees and resources.
−Removed: We have not previously undertaken a collaboration of this magnitude and focus.
−Removed: Although we may hire additional employees to increase our research and development group, it is not certain that we will be able to timely hire, or retain, qualified employees, in which case the work on our pipeline product candidates may be delayed until we are able to increase our staff such that we can meet our obligations under the AbbVie research plan and continue to develop our own product candidates.
We may form or seek collaborations or strategic alliances in the future for the development and commercialization of one or more of our product candidates or for new product candidates.
1 unchanged sentence
Our product candidate development programs and the potential commercialization of our product candidates will require substantial additional cash to fund expenses.
−Removed: To date, we have not partnered with a third party with respect to any of our product candidates.
−Removed: In the future, we may choose to partner with third parties for one or more of our product
−Removed: Table of Conte n t s
+Added: To date, we have not partnered with a third party with respect to commercializing of any of our product candidates.
+Added: We have entered into agreements with Pfizer with respect to certain information rights and rights of first negotiation with Pfizer regarding a BCMA Product Candidate, including our CB-011
+Added: product candidate.
+Added: In the future, we may choose to partner with third parties for one or more of our product candidates.
If we are unable to negotiate and enter into partnerships, we may have to curtail the development of the product candidate for which we are seeking to collaborate, reduce or delay its development program or one or more of our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense.
19 unchanged sentences
• we may lose certain valuable rights under circumstances identified in our collaborations, including if we undergo a change in control;
−Removed: Table of Conte n t s
• disputes may arise between our collaborator and us that may cause the collaborator to act in a manner adverse to us and could result in the delay or termination of the research, development, or commercialization of our product candidates or that result in costly litigation or arbitration that diverts our management’s attention and resources;
21 unchanged sentences
Many of our employees were previously, and our consultants are or were previously, employed at universities or research institutions, or at other biotechnology or pharmaceutical companies.
−Removed: Although we try to ensure that our employees, consultants, and third parties performing services for us do not use the confidential information of former employers or other companies in their work for us, we may be subject to claims that we or these individuals have used or disclosed confidential information or intellectual property, including trade secrets, of any such individual’s current or
−Removed: Table of Conte n t s
−Removed: former employer or other third party.
+Added: Although we try to ensure that our employees, consultants, and third parties performing services for us do not use the confidential information of former employers or other companies in their work for us, we may be subject to claims that we or these individuals have used or disclosed confidential information or intellectual property, including trade secrets, of any such individual’s current or former employer or other third party.
Litigation may be necessary to defend against these claims.
−Removed: If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.
+Added: If we fail in defending
+Added: any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.
Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to our management and employees.
4 unchanged sentences
Kanner, Ph.D., our chief scientific officer;
+Added: Tim Kelly, M.S./M.B.A., our chief technology officer;
Ruhi Khan, M.B.A., our chief business officer;
1 unchanged sentence
O’Byrne, M.B.A., our chief financial officer;
−Removed: and Syed Rizvi, M.D., our chief medical officer, as well as other members of our senior leadership team and our scientists.
+Added: and Reigin Zawadzki, our chief people officer;
+Added: as well as other members of our senior leadership team and our research and development team.
Certain of our scientists have greatly contributed to our intellectual property and are critical as we move our CRISPR Cas12a chRDNA technology platform forward.
10 unchanged sentences
To induce employees to remain at our company, in addition to salary and cash incentives, we provide equity awards that vest over time, the value of which may be significantly affected by movements in our stock price that are beyond our control and may be insufficient to counteract more lucrative offers from other companies.
−Removed: In addition, we rely on consultants and advisors, including our co-founders and scientific advisory board, or SAB, to assist us in formulating our research and development and commercialization strategy.
+Added: In addition, we rely on consultants and advisors, including our co-founders and SAB, to assist us in formulating our research and development and commercialization strategy.
Our consultants and advisors, including Drs.
8 unchanged sentences
• identifying, recruiting, integrating, maintaining, motivating, and integrating additional employees;
−Removed: Table of Conte n t s
• managing our internal development efforts effectively, including clinical trials and FDA or foreign regulatory authority review for our product candidates, while complying with our contractual obligations to third parties;
6 unchanged sentences
Our future financial performance and our ability to commercialize our product candidates, if approved, and compete effectively will depend, in part, on our ability to effectively manage the continuing development and expansion of our company.
−Removed: Our internal computer systems, or those of our third-party vendors, collaborators, consultants, or third parties performing services for us, may fail or suffer security breaches, which could result in a material disruption of the development of our product candidates and program research, compromise sensitive information related to our business, or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business .
−Removed: Our internal computer systems and those of our current and any future third-party vendors, collaborators, consultants, and third parties performing services for us, as well as our clinical sites and regulatory authorities, are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, and telecommunication and electrical failures.
−Removed: In addition, the COVID-19 pandemic has intensified our dependence on information technology systems as some of our critical business activities are currently being conducted remotely.
+Added: Our internal computer systems, or those of third parties with which we interact, may fail or suffer security breaches, which could result in a material disruption of the development of our product candidates and research programs, compromise sensitive information related to our business, or prevent us from accessing critical information, potentially exposing us to liability or otherwise adversely affecting our business.
+Added: Our internal computer systems, and those of third parties with which we interact, including our clinical sites, governmental agencies, CMOs, suppliers, CROs, clinical sites, and the like, are vulnerable to damage from computer viruses, ransomware, malware, data corruption, cyber-based attacks, phishing attacks, unauthorized access, natural disasters, terrorism, war, and telecommunication and electrical failures.
+Added: Attacks on information technology systems are increasing in their frequency, levels of persistence, sophistication and intensity, and they are being conducted by increasingly sophisticated and organized groups and individuals with a wide range of motives and expertise.
+Added: The prevalent use of mobile devices and unauthorized applications also increases the risk of data security incidents.
+Added: In addition, the increase in the number of our employees, and continued hybrid working environment, has intensified our dependence on internet technology systems as some of our critical business activities are currently being conducted remotely, which may create additional opportunities for cybercriminals to exploit vulnerabilities.
+Added: Furthermore, because the techniques used to obtain unauthorized access to, or to sabotage, systems change frequently and often are not recognized until launched against a target, we may be unable to anticipate these techniques or implement adequate preventative measures.
+Added: We may also experience security breaches that may remain undetected for an extended period.
+Added: Even if identified, we may be unable to adequately investigate or remediate incidents or breaches due to attackers increasingly using tools and techniques that are designed to circumvent controls, to avoid detection, and to remove or obfuscate forensic evidence.
Although we have not experienced any such material system failure, accident, or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a disruption of our product candidate development and our business operations, whether due to a loss of our trade secrets or other confidential information or other similar disruptions.
For example, the loss of clinical trial data from our current or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.
−Removed: To the extent that any disruption or security breach were to result in the theft or destruction of intellectual property, data, or other misappropriation of assets;
+Added: To the extent that any disruption or security breach were to result in the theft, loss, or destruction of intellectual property, data, or other misappropriation of assets;
financial loss;
−Removed: or otherwise compromise our confidential information, including trade secrets, and disrupt our operations, our competitive position could be harmed, and the further development and commercialization of our product candidates could be delayed.
+Added: or otherwise compromise our confidential information, including trade secrets, and disrupt our operations, our competitive position could be harmed, and the further development and commercialization of our product candidates could be delayed, any of which could materially adversely affect our business, financial condition, results of operations, and growth prospects.
We could be subject to risks caused by misappropriation, misuse, leakage, falsification, or intentional or accidental release or loss of information maintained in the information systems and networks of our company, our third-party vendors, and clinical sites, including personal information of our employees and, potentially, our clinical study patients, and company and vendor confidential data.
In addition, third parties may attempt to penetrate our systems or those of our vendors or fraudulently induce our personnel or the personnel of our vendors to disclose sensitive information to gain access to data and systems.
−Removed: We may experience threats to our data and systems, including malicious codes and viruses, phishing, and other cyber-attacks.
+Added: We may experience threats to our data and systems, including malicious codes and viruses, phishing, and other cyberattacks.
The number and complexity of these threats continue to increase over time.
3 unchanged sentences
Although we develop and maintain systems and controls designed to prevent these events from occurring, and we have a process to identify and mitigate threats, the development and maintenance of these systems, controls, and processes is costly and requires ongoing monitoring and updating as technologies change and efforts to overcome security measures become increasingly sophisticated.
−Removed: Table of Conte n t s
Moreover, despite our efforts, the possibility of these events occurring cannot be eliminated entirely.
29 unchanged sentences
Moreover, there is increasing stakeholder pressure on companies to diligence environmental, social, and governance matters in the supply chain.
−Removed: Negative publicity regarding production methods, alleged practices, or workplace or related conditions of any of our suppliers, CMOs, CROs, or third parties who perform services for us could adversely affect our reputation.
+Added: Negative publicity regarding production methods, alleged practices, or workplace or related conditions of any of our CMOs, suppliers, CROs, clinical sites, or third parties who perform services for us could adversely affect our reputation.
We could be forced to locate alternatives, which could increase our costs and result in delayed supply of components for, and manufacturing of, our product candidates, or other disruptions to our operations.
−Removed: Table of Conte n t s
Our insurance policies are expensive and only protect us from some business risks, which may leave us exposed to certain uninsured liabilities.
31 unchanged sentences
• a decline in our stock price.
−Removed: Table of Conte n t s
As a public company, we are obligated to develop and maintain proper and effective internal controls over financial reporting, and any failure to maintain the adequacy of these internal controls may adversely affect investor confidence in our company and, as a result, the value of our common stock.
−Removed: We are required, pursuant to Section 404 of the Sarbanes-Oxley Act of 2002 (the “Sarbanes-Oxley Act”), to furnish a report by management on, among other things, the effectiveness of our internal controls over financial reporting.
+Added: We are required, pursuant to Section 404 of the Sarbanes-Oxley Act of 2002 (“Sarbanes-Oxley Act”), to furnish a report by management on, among other things, the effectiveness of our internal controls over financial reporting.
This assessment includes disclosure of any material weaknesses identified by our management in our internal controls over financial reporting.
1 unchanged sentence
If we or our independent registered public accounting firm determines we have a material weakness in our internal controls over financial reporting, investors could lose confidence in the accuracy and completeness of our financial reports, the market price of our common stock could decline, and we could be subject to sanctions or investigations by the SEC or other regulatory authorities.
+Added: Internal control deficiencies could also result in a restatement of our financial results in the future.
Failure to remedy any material weakness or significant deficiency in our internal controls over financial reporting, or to implement or maintain other effective control systems required of public companies, could also restrict our future access to the capital markets.
8 unchanged sentences
We have also generated, and expect to continue to generate in the future, significant federal and state research and development tax credit carryforwards, and, beginning in 2022, we began to generate orphan drug credit carryforwards that are available to potentially offset federal and state income taxes, respectively, in future years, if any.
−Removed: Under the Tax Cuts and Jobs Act of 2017 (“TCJA”), as modified by the Coronavirus Aid, Relief and Economic Security Act (the “CARES Act”), our federal NOLs incurred in taxable years beginning after December 31, 2017 may be carried forward indefinitely.
+Added: Under the Tax Cuts and Jobs Act of 2017 (“TCJA”), as modified by the Coronavirus Aid, Relief and Economic Security Act (“CARES Act”), our federal NOLs incurred in taxable years beginning after December 31, 2017 may be carried forward indefinitely.
Additionally, for tax years beginning after December 31, 2020, the deductibility of federal NOLs incurred in taxable years beginning after December 31, 2017 is limited to 80% of our taxable income.
2 unchanged sentences
As a result, they may be unavailable to offset future taxes.
−Removed: In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended (the “Tax Code”), and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50 percentage point change, by value, in its equity ownership by certain stockholders over a rolling three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may be limited.
+Added: In addition, under Sections 382 and 383 of the Internal Revenue Code of 1986, as amended (“Tax Code”), and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50 percentage point change, by value, in its equity ownership by certain stockholders over a rolling three-year period, the corporation’s ability to use its pre-change NOL carryforwards and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may be limited.
We have experienced prior ownership changes in 2014, 2016, and most recently in July 2021 upon our IPO.
1 unchanged sentence
We have recorded a full valuation allowance for deferred tax assets, including NOLs and tax credits as of December 31, 2023.
−Removed: The issuance of common stock in the future, or shifts in the ownership of our common stock among certain stockholders, either separately or in combination, over time may result in a limitation under Sections 382 and 383 of the Code.
+Added: The issuance of common stock in the future, or shifts in the ownership of our common stock among certain stockholders, either separately or in combination, over time may result in a limitation under Sections
+Added: 382 and 383 of the Code.
In addition, at the state level, there may be periods during which the use of NOL carryforwards is suspended or otherwise limited, which could accelerate or permanently increase state taxes owed.
−Removed: For example, California imposed limits on the use of California state NOLs and tax credits to offset California taxable income in years beginning
−Removed: Table of Conte n t s
−Removed: after 2019 and before 2022.
+Added: For example, California imposed limits on the use of California state NOLs and tax credits to offset California taxable income in years beginning after 2019 and before 2022.
If an ownership change occurs and we earn taxable income in future years, the limitation on our ability to use our NOLs and other tax attribute carryforwards could adversely affect our future operating results by increasing our future income tax liabilities.
See Note 15 to the consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information.
−Removed: The COVID-19 pandemic or other pandemics or public health crises may adversely impact our business, financial condition, and results of operations, including our preclinical studies and clinical trials, and may cause substantial disruption in the financial markets and adversely impact economies worldwide.
−Removed: We may experience disruptions related to the COVID-19 pandemic or other pandemics or public health crises that could severely impact our business, preclinical studies, clinical trials, and commercialization activities, including:
+Added: Pandemics or other public health crises, such as the prior COVID-19 pandemic, may adversely impact our business, financial condition, and results of operations, including our preclinical studies and clinical trials, and may cause substantial disruption in the financial markets and adversely impact economies worldwide.
+Added: We may experience disruptions related to pandemics or other public health crises that could severely impact our business, preclinical studies, clinical trials, and commercialization activities, including:
• halting or suspending enrollment in our clinical trials;
• delays or difficulties in enrolling and retaining patients in our clinical trials;
−Removed: • interruption of key clinical trial activities, such as clinical trial site data monitoring and efficacy, safety and translational data collection, processing and analyses, due to limitations on travel imposed or recommended by federal, state, or local governments, employers and others or interruption of clinical trial subject visits, which may impact the collection and integrity of subject data and clinical study endpoints;
−Removed: • requirements to change the ways in which our preclinical studies and clinical trials are conducted due to governmental regulations as part of a response to the COVID-19 pandemic or other pandemics or other public health crises, which may result in unexpected costs, delays, or discontinuation of our preclinical studies and clinical trials altogether;
−Removed: • increased adverse events and deaths in our clinical trials due to COVID-19-related or other pandemic-related infections, which may result in increased complications due to immunosuppression from our lymphodepletion regimen;
−Removed: • increased rates of patients withdrawing from our clinical trials following enrollment as a result of contracting COVID-19 or being forced to quarantine due to other public health crises;
+Added: • interruption of key clinical trial activities, such as clinical trial site data monitoring and efficacy, safety and translational data collection, and processing and analyses, due to limitations on travel imposed or recommended by federal, state, or local governments, employers and others or interruption of clinical trial subject visits, which may impact the collection and integrity of subject data and clinical study endpoints;
+Added: • requirements to change the ways in which our preclinical studies and clinical trials are conducted due to governmental regulations as part of a response to pandemics or other public health crises, which may result in unexpected costs, delays, or discontinuation of our preclinical studies and clinical trials altogether;
+Added: • increased adverse events and deaths in our clinical trials due to pandemic-related infections;
+Added: • increased rates of patients withdrawing from our clinical trials following enrollment as a result of contracting certain diseases or being forced to quarantine due to other public health crises;
• diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials;
• interruption or delays in the operations of the FDA and comparable foreign regulatory agencies and necessary interactions with such regulatory agencies due to limitations in employee resources, limitations on travel, forced furlough of government employees, or diversion of resources, which would impact review and approval timelines;
−Removed: • interruption of, or delays in receiving, supplies of components for our product candidates from our suppliers, including the supply of healthy donor cells, and delays or suspension in manufacturing by our CMOs due to staffing shortages, production slowdowns or stoppages, and disruptions in delivery systems, or due to prioritization of production for COVID-19-specific (or other pandemic-related) therapies or vaccines;
+Added: • interruption of, or delays in receiving, supplies of components for our product candidates from our suppliers, including the supply of healthy donor cells, and delays or suspension in manufacturing by our CMOs due to staffing shortages, production slowdowns or stoppages, and disruptions in delivery systems, or due to prioritization of production for pandemic-related therapies or vaccines;
• limitations on employee resources that would otherwise be focused on advancing our business, including because of sickness of employees or their families, including our executive officers and other key employees, the desire of employees to avoid contact with large groups of people, an increased reliance on working from home, or mass transit disruptions;
• significant disruptions and volatility in the financial markets.
−Removed: The extent to which the COVID-19 pandemic or other public health crises may impact our business, research, preclinical studies and clinical trials, productivity of our employees, supply chains, and access to capital or business development activities will depend on future developments, which are highly uncertain at this time.
−Removed: To the extent the COVID-19 pandemic or other public health crisis adversely affects our business, financial condition, results of operations, and prospects, it may also have the effect of amplifying many of the other risks described in this Risk Factors section, such as those relating to the timing and results of our current and future clinical trials and our financing needs.
−Removed: See the Impact of the COVID-19 Pandemic in the Management’s Discussion and Analysis of Financial Condition and Results of Operations
−Removed: Table of Conte n t s
−Removed: section in Part II, Item 7 of this Annual Report on Form 10-K for more information about the impact of COVID-19 on our business.
+Added: The extent to which pandemics or other public health crises may impact our business, research, preclinical studies and clinical trials, productivity of our employees, supply chains, and access to capital or business development activities will depend on future developments, which are highly uncertain at this time.
+Added: To the extent pandemics or other public health crisis adversely affects our business, financial condition, results of operations, and prospects, it may also have the effect of amplifying many of the other risks described in this Risk Factors section, such as those relating to the timing and results of our current and future clinical trials and our financing needs.
Business disruptions could seriously harm our future revenue and financial condition and increase our costs and expenses.
−Removed: In addition to the business disruptions caused by public health crises or potential cybersecurity attacks, our operations, and those of our suppliers, CMOs, CROs, and clinical trial sites, could be subject to disruptions, including those caused by earthquakes, power shortages or outages, telecommunications failures, water shortages or outages, floods, hurricanes, typhoons, fires, extreme weather conditions, epidemics and pandemics, and other natural or man-made disasters or business interruptions.
+Added: In addition to the business disruptions caused by public health crises or potential cybersecurity attacks, our operations, and those of our CMOs, suppliers, CROs, and clinical trial sites, could be subject to disruptions, including those caused by earthquakes, power shortages or outages, telecommunications failures, water shortages or outages, floods, hurricanes, typhoons, fires, extreme weather conditions, epidemics and pandemics, and other natural or man-made disasters or business interruptions.
The occurrence of any of these business disruptions could seriously harm our business, financial condition, results of operations, and prospects, and increase our costs and expenses.
−Removed: Our ability to manufacture our product candidates could be disrupted if our operations or those of our suppliers, CMOs, CROs, or clinical trial sites are affected by a natural or man-made disaster or other business interruption.
+Added: Our ability to manufacture our product candidates could be disrupted if our operations or those of our CMOs, suppliers, CROs, or clinical trial sites are affected by a natural or man-made disaster or other business interruption.
Our corporate headquarters are located in California near major earthquake faults and fire zones.
11 unchanged sentences
If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions for our product candidates, which could have a material adverse effect on our business.
+Added: Adverse developments affecting the financial services industry could adversely affect our current and projected business operations and our financial condition and results of operations.
+Added: Adverse developments that affect financial institutions, such as events involving liquidity that are rumored or actual, have in the past and may in the future lead to bank failures and market-wide liquidity problems.
+Added: For example, on March 10, 2023, Silicon Valley Bank (“SVB”) was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation (“FDIC”) as receiver.
+Added: Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp.
+Added: were each put into receivership.
+Added: Although the U.S.
+Added: Department of Treasury, FDIC, and Federal Reserve Board have implemented a program to provide up to $25 billion of loans to financial institutions secured by certain of such government securities held by financial institutions to mitigate the risk of potential losses on the sale of such instruments, widespread demands for customer withdrawals or other liquidity needs of financial institutions for immediate liquidity may exceed the capacity of such program, there is no guarantee that such programs will be sufficient.
+Added: Additionally, it is uncertain whether the U.S.
+Added: Department of Treasury, FDIC, and Federal Reserve Board will provide access to uninsured funds in the future in the event of the closure of other banks or financial institutions, or that they would do so in a timely fashion.
+Added: Although we have not experienced any adverse impact to our liquidity or to our current and projected business operations, financial condition, or results of operations as a result of the matters relating to these banks, uncertainty remains over liquidity concerns in the broader financial services industry, and our industry as a whole may be adversely impacted in ways that we cannot predict at this time.
+Added: Although we assess our banking relationships as we believe necessary or appropriate, our access to cash in amounts adequate to finance our current and projected future business operations could be significantly impaired by factors that affect the financial institutions with which we have banking relationships.
+Added: These factors could include, among others, events such as liquidity constraints or failures, the ability to perform obligations under various types of financial, credit or liquidity agreements or arrangements, disruptions or instability in the financial services industry or financial markets, or concerns or negative expectations about the prospects for companies in the financial services industry.
+Added: These factors could also include factors involving financial markets or the financial services industry generally.
+Added: The results of events or concerns that involve one or more of these factors could include a variety of material and adverse impacts on our current and projected business operations and our financial condition and results of operations.
+Added: These could include, but may not be limited to, delayed access to deposits or other financial assets or the uninsured loss of deposits or other financial assets, termination of cash management arrangements, and/or delays in accessing or actual loss of funds subject to cash management arrangements.
+Added: In addition, widespread investor concerns regarding the U.S.
+Added: or international financial systems could result in less favorable commercial financing terms, including higher interest rates or costs and tighter financial and operating covenants, or systemic limitations on access to credit and liquidity sources, thereby making it more difficult for us to acquire financing on acceptable terms or at all.
+Added: Any decline in available funding or access to our cash and liquidity resources could, among other risks, adversely impact our ability to meet our operating expenses, financial obligations or fulfill our other obligations, result in breaches of our financial and/or contractual obligations or result in violations of federal or state wage and hour laws.
+Added: Any of these impacts, or any other impacts resulting from the factors described above or other related or similar factors not described above, could have material adverse impacts on our liquidity and our current and/or projected business operations and financial condition and results of operations.
+Added: We maintain our cash at financial institutions, often in balances that exceed federally insured limits.
+Added: We maintain the majority of our cash and cash equivalents in accounts at banking institutions in the United States that we believe are of high quality.
+Added: Cash held in these accounts often exceed the FDIC insurance limits.
+Added: If such banking institutions were to fail, we could lose all or a portion of amounts held in excess of such insurance limitations.
+Added: As noted above, the FDIC recently took control of certain banks.
+Added: In the event of failure of any of the financial institutions where we maintain our cash and cash equivalents, there can be no assurance that we would be able to access uninsured funds in a timely manner or at all.
+Added: Any inability to access or delay in accessing these funds could adversely affect our business and financial position.
Unfavorable global economic conditions could adversely affect our business, financial condition, or results of operations.
Our business, financial condition, results of operations, or prospects could be adversely affected by general conditions in the global economy and in the global financial markets.
−Removed: A severe or prolonged economic downturn, including as a result of the COVID-19 pandemic, the ongoing war in Ukraine, interest rate fluctuations, rising inflation, recession, or other global financial or geopolitical crises, could result in a variety of risks to our business, including weakened demand for our product candidates, if approved, or our ability to raise additional capital when needed on acceptable terms, if at all.
−Removed: A weak or declining economy could also strain our suppliers and CMOs, possibly resulting in supply or manufacturing disruption.
+Added: A severe or prolonged economic downturn, including as a result of pandemics or other public health crises, the ongoing war between Russia and Ukraine and the ongoing conflict in the Middle East, interest rate fluctuations, rising inflation, recession, or other global financial, geopolitical crises or macroeconomic factors, could result in a variety of risks to our business, including weakened demand for our product candidates, if approved, or our ability to raise additional capital when needed on acceptable terms, if at all.
+Added: Recent global events such as supply chain constraints have led to higher inflation, which, if sustained, could have a negative impact on our product development and operations.
+Added: If inflation or other factors were to significantly increase our business costs, our ability to develop our current pipeline and new therapeutic product candidates may be negatively affected.
+Added: Global conflicts or a weak or declining economy may increase the likelihood disruptions of our clinical trials or manufacturing and supply of our product candidates.
+Added: We are currently conducting our ANTLER clinical trial at sites in Israel and, although we have not experienced delays or interruptions to date, given the conflict in the Middle East, we may experience disruptions at these sites in the future.
+Added: Additionally, any supply disruptions could make it more difficult for us to find favorable pricing and reliable sources for the materials we need, which would increase pressure on our costs and increase the risk that we may be unable to acquire the necessary materials to successfully manufacture our product candidates.
+Added: Current capital market conditions, including the impact of inflation, have increased borrowing rates and can be expected to significantly increase the cost of capital as compared to prior periods and could also affect our ability to raise capital on favorable terms, or at all, in order to fund our operations.
+Added: Similarly, these macroeconomic factors could affect the ability of our third-party suppliers and CMOs to manufacture clinical trial materials for our product candidates.
+Added: Furthermore, we currently conduct some clinical trials outside of the United States, and unfavorable global conditions could affect these trials.
Any of the foregoing could harm our business and we cannot anticipate all of the ways in which such conditions could adversely impact our business.
6 unchanged sentences
• results of preclinical studies, clinical trials, or regulatory approvals of product candidates of our competitors, or announcements about new research programs or product candidates of our competitors;
−Removed: Table of Conte n t s
• adverse regulatory decisions, including failure to receive regulatory approval of one or more of our product candidates;
7 unchanged sentences
• acceptance or lack of acceptance of allogeneic products;
−Removed: • inability to meet the obligations under our collaboration agreement with AbbVie;
−Removed: • inability to obtain additional collaboration partners;
+Added: • inability to obtain collaboration partners;
• the recruitment and retention of key personnel;
8 unchanged sentences
• market conditions in the pharmaceutical and biotechnology sectors;
−Removed: • general economic, industry, and market conditions;
+Added: • general economic and political conditions such as recessions, inflationary pressures, interest rates, fuel prices, elections, drug pricing policies, international currency fluctuations, acts of war or terrorism, geopolitical events and public health crises;
• the other factors described in this Risk Factors section.
We are subject to securities class action litigation, which may result in substantial costs and a diversion of management's attention and resources, which could harm our business.
−Removed: In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities, and we are litigating a class action complaint in the United States District Court for the Northern District of California, filed by a purported stockholder against us and certain of our directors and officers.
+Added: In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities, and we are currently litigating a class action complaint in the U.S.
+Added: District Court for the Northern District of California, filed by purported stockholders against us and certain of our directors, officers, and underwriters.
See Legal Proceedings in Item 3 of this Annual Report on Form 10-K for additional information.
2 unchanged sentences
Defending against the current litigation and any future litigation could result in substantial costs and a diversion of management’s attention and resources, which could harm our business.
−Removed: Table of Conte n t s
If securities analysts do not publish research or reports about our business or if they publish negative evaluations of our stock, the price of our stock could decline.
6 unchanged sentences
As of March 5, 2024, we had 90,314,501 shares of common stock outstanding.
−Removed: Most of these shares can be sold at any time unless held by one of our affiliates, in which case the resale of those securities will be subject to volume limitations and other restrictions under Rule 144 of the Securities Act.
+Added: Most of these shares can be sold at any time unless held by one of our affiliates, in which case the resale of those securities will be subject to volume limitations and other restrictions under Rule 144 of the Securities Act of 1933, as amended (the “Securities Act”).
We have also registered all shares of common stock that we may issue under our equity compensation plans or that are issuable upon exercise of outstanding options or other equity awards.
5 unchanged sentences
These exemptions include not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act;
−Removed: not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements;
+Added: not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board (“PCAOB”) regarding mandatory audit firm rotation or a supplement to the auditor’s report providing additional information about the audit and the financial statements;
reduced disclosure obligations regarding executive compensation;
10 unchanged sentences
If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.
−Removed: Table of Conte n t s
We have incurred, and will continue to incur, increased costs as a result of operating as a public company, and our management will continue to devote substantial time to compliance initiatives and corporate governance practices.
25 unchanged sentences
As a result, investors seeking cash dividends should not invest in our common stock.
−Removed: Table of Conte n t s
Provisions in our amended and restated certificate of incorporation, our amended and restated bylaws, and Delaware law may have anti-takeover effects that could discourage an acquisition of us by others, even if an acquisition would be beneficial to our stockholders.
21 unchanged sentences
In the event that our common stock is delisted from Nasdaq and is not eligible for quotation or listing on another market or exchange, trading of our common stock could be conducted only in the over-the-counter market or on an electronic bulletin board established for unlisted securities such as the Pink Sheets or the OTC Bulletin Board.
−Removed: If this were to occur, it could become more difficult to dispose of, or obtain accurate price quotations for, our common stock and there would likely also be a reduction
−Removed: Table of Conte n t s
−Removed: in our coverage by securities analysts and the news media, which could cause the price of our common stock to decline further.
+Added: If this were to occur, it could become more difficult to dispose of, or obtain accurate price quotations for, our common stock and there would likely also be a reduction in our coverage by securities analysts and the news media, which could cause the price of our common stock to decline
Furthermore, if we were to be delisted from Nasdaq, our common stock would cease to be recognized as “covered securities” and we would be subject to regulation in each state in which we offer our securities.
19 unchanged sentences
If a court were to find the exclusive forum provision in our amended and restated certificate of incorporation to be inapplicable or unenforceable in an action, we may incur further significant additional costs associated with resolving the dispute in other jurisdictions, all of which could seriously harm our business.
−Removed: Unresolved Staff Comments.
−Removed: Not applicable
−Removed: Table of Conte n t s
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.