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What changed in Caribou Biosciences, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Caribou Biosciences, Inc.'s 2023 and 2024 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2024 report.

+736 added−797 removedSource: 10-K (2025-03-10) vs 10-K (2024-03-11)

Top changes in Caribou Biosciences, Inc.'s 2024 10-K

736 paragraphs added · 797 removed · 516 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

213 edited+125 added−188 removed167 unchanged
Biggest changeCB-010 has received regenerative medicine advanced therapy (“RMAT”) designation for r/r LBCL, fast track designation for relapsed or refractory B cell non-Hodgkin lymphoma (“r/r B-NHL”), and orphan drug designation for follicular lymphoma (“FL”) from the U.S. Food and Drug Administration (“FDA”). CB-010 is being evaluated in our ongoing ANTLER phase 1 clinical trial in patients with r/r B-NHL.
Biggest changeWe are advancing our pipeline of allogeneic CAR-T cell therapies with the following four clinical development programs targeting the treatment of hematologic malignancies and autoimmune diseases: • CB-010: an allogeneic anti-CD19 CAR-T cell therapy, being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (“r/r B-NHL”) in our ANTLER phase 1 clinical trial • CB-010: also being evaluated in patients with lupus nephritis (“LN”) and in patients with extrarenal lupus (“ERL”) in our GALLOP phase 1 clinical trial • CB-011: an allogeneic anti-BCMA CAR-T cell therapy, being evaluated in patients with relapsed or refractory multiple myeloma (“r/r MM”) in our CaMMouflage phase 1 clinical trial • CB-012: an allogeneic anti-CLL-1 CAR-T cell therapy, being evaluated in patients with relapsed or refractory acute myeloid leukemia (“r/r AML”) in our AMpLify phase 1 clinical trial CB-010 has received regenerative medicine advanced therapy (“RMAT”) designation for relapsed or refractory large B cell lymphoma (“r/r LBCL”) as well as fast track designations for r/r B-NHL and refractory systemic lupus erythematosus (“SLE”) from the U.S.
We seek to protect these trade secrets and other confidential information, in part, by entering into confidentiality agreements with parties who have access to them. We also enter into confidentiality and invention assignment agreements with our employees and our agreements with consultants include invention assignment obligations. Competition We currently compete across the fields of genome editing and cell therapy.
We seek to protect these trade secrets and other confidential information, in part, by entering into confidentiality agreements with parties who have access to them. We also enter into confidentiality and invention assignment agreements with our employees and our agreements with consultants include invention assignment obligations. Competition We currently compete across the fields of cell therapy and genome editing.
Memorial Sloan Kettering Cancer Center On November 13, 2020, we entered into an Exclusive License Agreement with MSKCC (“MSKCC Agreement”), under which we exclusively licensed from MSKCC know-how, biological materials, and related patent families to fully human scFvs targeting CLL-1 (also known as CD371) for use in T cells, NK cells, and genome-edited iPSCs for allogeneic CLL-1-targeted cell therapy.
Memorial Sloan Kettering Cancer Center On November 13, 2020, we entered into an Exclusive License Agreement with MSKCC (as amended, “MSKCC Agreement”), under which we exclusively licensed from MSKCC know-how, biological materials, and related patent families to fully human scFvs targeting CLL-1 (also known as CD371) for use in T cells, NK cells, and genome-edited iPSCs for allogeneic CLL-1-targeted cell therapy.
Later discovery of previously unknown problems with our product, including adverse events of unanticipated severity or frequency, issues with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, imposition of post-marketing studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS program.
Later discovery of previously unknown problems with our product, including adverse events of unanticipated severity or frequency, issues with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information, imposition of post-marketing studies or clinical trials to assess new safety risks, or imposition of distribution or other restrictions under a REMS.
Orphan Drug Designation Orphan drug designation may be available for drugs that are intended for rare diseases or conditions, defined as (i) a disease or condition that affects fewer than 200,000 individuals in the United States or (ii) a disease or condition that affects more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making available a biologic for the disease or condition will be recovered from sales of the product in the United States.
Orphan Drug Designation Orphan drug designation is available for drugs that are intended for rare diseases or conditions, defined as (i) a disease or condition that affects fewer than 200,000 individuals in the United States or (ii) a disease or condition that affects more than 200,000 individuals in the United States and for which there is no reasonable expectation that the cost of developing and making available a biologic for the disease or condition will be recovered from sales of the product in the United States.
Moreover, a patent can only be restored once, and thus, if a single patent is applicable to multiple products, it can only be extended based on one product. Similar provisions are available in Europe and certain other foreign jurisdictions to extend the term of a patent that covers an approved product.
Moreover, a patent can only be restored once and, if a single patent is applicable to multiple products, it can only be extended based on one product. Similar provisions to extend the term of a patent that covers an approved product are available in Europe and certain other foreign jurisdictions .
The potential payments are based on multiples of the fair market value of our common stock compared with a split-adjusted initial share price of $5.1914 per share, as subject to future adjustments for stock splits, during a specified time period described below.
The potential payments are based on multiples of the fair value of our common stock compared with a split-adjusted initial stock price of $5.1914 per share, as subject to future adjustments for stock splits, during a specified time period described below.
The MSKCC Agreement includes certain diligence milestones that we must meet; provided, however, that these may be extended upon payment of additional fees. MSKCC is entitled to certain success payments if our stock value increases by certain multiples.
The MSKCC Agreement includes certain diligence milestones that we must meet; provided, however, that these may be extended by us upon payment of additional fees. MSKCC is entitled to certain success payments if our stock value increases by certain multiples.
We use multiple CMOs to individually manufacture the starting materials for our product candidates, including cGMP chRDNA guides, Cas9 and Cas12a proteins, and AAV6 vectors used in the manufacture of our CAR-T cells.
We use multiple CMOs to individually manufacture the critical and starting materials for our product candidates, including cGMP chRDNA guides, Cas9 and Cas12a proteins, and AAV6 vectors used in the manufacture of our CAR-T cells.
The FDA strictly regulates marketing, labeling, advertising, and promotion of licensed and approved products that are placed on the market. Pharmaceutical products may be promoted only for the approved indications and in accordance with the provisions of the approved label.
The FDA strictly regulates marketing, labeling, advertising, and promotion of licensed and approved products that are placed on the market. Pharmaceutical products may be promoted only for the approved indications and in accordance with the provisions of the approved labeling.
In a second model, we evaluated CLL-1-specific CB-012 CAR-T cells compared to equivalent CAR-T cells that lacked the PD-1 KO in a xenograft model of CLL-1+ PD-L1+ tumor cells to evaluate the impact of the PD-1 knockout in CB-012.
In a second model, we evaluated CLL-1-specific CB-012 CAR-T cells compared to equivalent CAR-T cells that lacked the PD-1 knockout in a xenograft model of CLL-1+ PD-L1+ tumor cells to evaluate the impact of the PD-1 knockout in CB-012.
Our product candidates may obtain breakthrough therapy designations if they are intended, either alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that our product candidates may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
Our product candidates may obtain breakthrough therapy designations if they are intended, either alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that our product candidates may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
Pursuant to the Leaseback Agreement, in exchange for Intellia’s grant to us of an exclusive license to certain intellectual property relating to CRISPR-Cas9, including Cas9 chRDNAs, for use solely in the manufacture of our CB-010 product candidate, we paid Intellia an upfront cash payment of $1.0 million and will pay up to $23.0 million in potential future regulatory and sales milestones.
Pursuant to the Leaseback Agreement, in exchange for Intellia’s grant to us of an exclusive license to certain intellectual property relating to CRISPR-Cas9, including Cas9 chRDNAs, for use solely in the manufacture of our CB-010 product candidate, we paid Intellia an upfront cash payment of $1.0 million and we will owe up to $23.0 million in potential future regulatory and sales milestones.
To date, we have entered into over 25 sublicensing agreements in a variety of fields such as human therapeutics, forestry, agriculture, research reagents, transgenic animals, certain livestock targets, internal research, bioproduction, cell lines, and microbial applications that include the CVC IP as well as other Cas9 intellectual property owned or controlled by us.
To date, we have entered into over 30 sublicensing agreements in a variety of fields such as human therapeutics, forestry, agriculture, research reagents, transgenic animals, certain livestock targets, internal research, bioproduction, cell lines, and microbial applications that include the CVC IP as well as other Cas9 intellectual property owned or controlled by us.
Physician Payments Sunshine Act, or Open Payments program, created under the Affordable Care Act, which requires certain manufacturers of drugs, devices, biologics, and medical supplies to report annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to payments, including certain product development activities such as clinical trials, and other transfers of value made by that entity to covered recipients, currently defined to include doctors, dentists, optometrists, podiatrists, chiropractors, teaching hospitals, physician assistants, nurse practitioners, and certain other healthcare providers and requires certain manufacturers and applicable group purchasing organizations to report ownership and investment interests held by physicians or their immediate family members; • U.S. price reporting laws, which require companies to calculate and report complex pricing metrics in an accurate and timely manner to government programs.
Physician Payments Sunshine Act, or Open Payments program, created under the Affordable Care Act, which requires certain manufacturers of drugs, devices, biologics, and medical supplies to report annually to the Centers for Medicare & Medicaid Services (“CMS”) information related to payments, including certain product development activities such as clinical trials, and other transfers of value made by that entity to covered recipients, currently defined to include doctors, dentists, optometrists, podiatrists, chiropractors, teaching hospitals, physician assistants, nurse practitioners, and certain other healthcare providers and requires certain manufacturers and applicable group purchasing organizations to report ownership and investment interests held by physicians or their immediate family members; 34 Tabl e of Contents • U.S. price reporting laws, which require companies to calculate and report complex pricing metrics in an accurate and timely manner to government programs.
Other potential consequences of a failure to comply with regulatory requirements include: • restrictions on the marketing or manufacturing of our product, complete withdrawal of our product from the market, or product recalls; • fines, untitled or warning letters, or holds on post-approval clinical trials; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of our product license approvals; 41 Table of Contents • product seizure or detention, or refusal to permit the import or export of products or the raw materials or ingredients that are needed for product manufacture; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences of a failure to comply with regulatory requirements include: • restrictions on the marketing or manufacturing of our product, complete withdrawal of our product from the market, or product recalls; • fines, untitled or warning letters, or holds on post-approval clinical trials; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of our product license approvals; • product seizure or detention, or refusal to permit the import or export of products or the raw materials or ingredients that are needed for product manufacture; or • injunctions or the imposition of civil or criminal penalties.
We have registered “CARIBOU,” “CARIBOU BIOSCIENCES,” “SITE-SEQ,” and the Caribou logo as trademarks in relevant classes and jurisdictions in the United States and certain other jurisdictions. Furthermore, we rely upon trade secrets, know-how, continuing technological innovation and potential in-licensing opportunities to develop and maintain our competitive position.
We have registered “CARIBOU,” “CARIBOU BIOSCIENCES,” “SITE-SEQ,” and the Caribou logo as trademarks in relevant classes and jurisdictions in the United States, European Union, and certain other jurisdictions. Furthermore, we rely upon trade secrets, know-how, continuing technological innovation and potential in-licensing opportunities to develop and maintain our competitive position.
ETASU can include, but is not limited to, specific or special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
ETASU can include, but are not limited to, specific or special training or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring, and the use of patient registries. The FDA may prevent or limit further marketing of a product based on the results of post-marketing studies or surveillance programs.
Even if a product is considered to be a reference product eligible for exclusivity, another company could market a competing version of that product if the FDA approves a full BLA for such product containing our own preclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity, and potency of the product.
Even if a product is considered to be a reference product eligible for exclusivity, another company could market a competing version of that product if the FDA approves a full BLA for such product containing our own nonclinical data and data from adequate and well-controlled clinical trials to demonstrate the safety, purity, and potency of the product.
Additionally, we have extensive patent protection on CRISPR Type I systems, CRISPR-Cas9 methods and compositions, and other genome-editing technologies. The patent term in the United States and other countries is 20 years from the date of filing of the first non-provisional application to which priority is claimed.
Additionally, we have substantial patent protection on CRISPR Type I systems, CRISPR-Cas9 methods and compositions, and other genome-editing technologies. The patent term in the United States and other countries is 20 years from the date of filing of the first non-provisional application to which priority is claimed.
The FDA has 60 calendar days after submission of a BLA to conduct an initial review to determine whether the BLA is acceptable for filing based on the agency’s threshold determination that the BLA is sufficiently complete to permit substantive review. Once the submission has been accepted for filing, the FDA begins an in-depth review of the application.
The FDA has 60 calendar days after submission of a BLA to conduct an initial review to determine whether the BLA is acceptable for filing based on the agency’s threshold determination that the BLA is sufficiently complete to permit substantive review. Once the submission has been filed, the FDA begins an in-depth review of the application.
On the basis of the FDA’s evaluation of the application and accompanying information, including the results of the inspection of the manufacturing facilities and any FDA audits of nonclinical study and clinical trial sites to ensure compliance with cGMPs and cGCPs, respectively, the FDA may issue an approval letter or a complete response letter.
On the basis of the FDA’s evaluation of the application and accompanying information, including the results of the inspection of the manufacturing facilities and any FDA audits of nonclinical study and clinical trial sites to ensure compliance with cGMPs and cGCPs, respectively, the FDA will issue an approval letter or a complete response letter.
False Claims Act; • the U.S. federal Beneficiary Inducement Statute, which prohibits, among other things, the offering or giving of remuneration, which includes, without limitation, any transfer of items or services for free or for less than fair market value, with limited exceptions, to a Medicare or Medicaid beneficiary that the person knows or should know is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of items or services reimbursable by a federal or state health program; • the U.S.
Beneficiary Inducement Statute, which prohibits, among other things, the offering or giving of remuneration, which includes, without limitation, any transfer of items or services for free or for less than fair market value, with limited exceptions, to a Medicare or Medicaid beneficiary that the person knows or should know is likely to influence the beneficiary’s selection of a particular provider, practitioner, or supplier of items or services reimbursable by a federal or state health program; • the U.S.
In this guidance the FDA outlined factors that sponsors should consider in conducting clinical trials using CAR-Ts, including defining appropriate study populations based on potential toxicities of CAR-T cells, such as 37 Table of Contents cytokine-release syndrome and neurological toxicities, diagnostic tests that can identify patients with tumors that have the target antigens, selection of appropriate dosage levels based on viable transduced CAR-T cells, etc.
In this guidance the FDA outlined factors that sponsors should consider in conducting clinical trials using CAR-Ts, including defining appropriate study populations based on potential toxicities of CAR-T cells, such as cytokine-release syndrome and neurological toxicities, diagnostic tests that can identify patients with tumors that have the target antigens, selection of appropriate dosage levels based on viable transduced CAR-T cells, etc.
The patent portfolio owned by us includes U.S. and foreign patents and patent applications covering methods and compositions relating generally to our Cas9 chRDNA and Cas12a chRDNA guides (which, for granted U.S. patents, without PTA or PTE, will expire in 2036).
The patent portfolio owned by us includes U.S. and foreign patents and patent applications covering methods and compositions relating generally to our Cas9 chRDNA and Cas12a chRDNA technologies (which, for granted U.S. patents, without PTA or PTE, will expire in 2036).
We live by our core values: we are driven by patient needs, innovation is in our chRDNA, together we are stronger, and integrity and ethics guide our decision making. We have built a culture where employees are empowered, their ideas are taken seriously, and their contributions are recognized.
Our culture is built around our core values: we are driven by patient needs, innovation is in our chRDNA, together we are stronger, and integrity and ethics guide our decision making. We have built a culture where employees are empowered, their ideas are taken seriously, and their contributions are recognized.
See Risk Factors - “Our ability to continue to receive licensing revenue and to enter into 28 Table of Contents 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.
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.
Regulation and Procedures Governing Approval of Medicinal Products in Other Countries In order to market any product outside of the United States, we must also comply with numerous and comprehensive regulatory requirements of other countries and jurisdictions, regarding quality, safety, and efficacy, and 43 Table of Contents governing, among other things, clinical trials, marketing authorization, post-authorization requirements, commercial sales, import and export, reimbursement, and distribution of products.
Regulation and Procedures Governing Approval of Medicinal Products in Other Countries In order to market any product outside of the United States, we must also comply with numerous and comprehensive regulatory requirements of other countries and jurisdictions, regarding quality, safety, and efficacy, and governing, among other things, clinical trials, marketing authorization, post-authorization requirements, commercial sales, import and export, reimbursement, and distribution of products.
Furthermore, the Food and Drug Omnibus Reform Act of 2022 requires clinical trial sponsors to submit a diversity action plan for clinical trials, unless a waiver is granted by the FDA for reasons such as prevalence of the disease or condition, impracticality of implementing such a diversity action plan, or if such implementation would be against the interest of public health during a public health emergency.
Furthermore, the Food and Drug Omnibus Reform Act of 2022 (“FDORA”) requires a clinical trial sponsor to submit a diversity action plan for clinical trials, unless a waiver is granted by the FDA for reasons such as prevalence of the disease or condition, impracticality of implementing such a diversity action plan, or if such implementation would be against the interest of public health during a public health emergency.
Review and Approval of a BLA The results of product candidate development, preclinical testing, and clinical trials, including negative or ambiguous results as well as positive findings, are submitted to the FDA as part of a BLA requesting a license to market the product.
Review and Approval of a BLA The results of product candidate development, nonclinical testing, and clinical trials, including negative or ambiguous results as well as positive findings, are submitted to the FDA as part of a BLA requesting a license to market the product.
Under the PHSA, the FDA may approve a BLA if it determines that our product candidate is safe, pure, and potent and the manufacturing facility meets standards designed to ensure that our product continues to be safe, pure, and potent.
Under the PHSA, the FDA will approve a BLA if it determines that our product candidate is safe, pure, and potent and the manufacturing facility meets standards designed to ensure that our product continues to be safe, pure, and potent.
In no event will the combination of success payments and any change of control payment exceed $35.0 million. 26 Table of Contents We may terminate the MSKCC Agreement upon 90 calendar days’ prior written notice to MSKCC. MSKCC may terminate the agreement in the event of our uncured material breach, bankruptcy, or criminal activity.
In no event will the combination of success payments and any change of control payment exceed $35.0 million. We may terminate the MSKCC Agreement upon 90 calendar days’ prior written notice to MSKCC. MSKCC may terminate the agreement in the event of our uncured material breach, bankruptcy, or criminal activity.
The lack of endogenous HLA class I antigens and the presence of only HLA-E are 10 Table of Contents designed to prevent the patient’s T cells and NK cells from rapidly rejecting the allogeneic therapy. These cells are unlikely to persist indefinitely, and ultimately other types of immune cells in the patient will eliminate the allogeneic CAR-T cells.
The lack of endogenous HLA class I antigens and the presence of only HLA-E are designed to prevent the patient’s T cells and NK cells from rapidly rejecting the allogeneic therapy. These cells are unlikely to persist indefinitely, and ultimately other types of immune cells in the patient will eliminate the allogeneic CAR-T cells.
The FDA may take certain actions with respect to product candidates with such designations, including holding meetings with us throughout the development process, providing timely advice to us regarding development and approval, involving more senior staff in the review process, assigning a cross-disciplinary project lead for the review team, and taking other steps to design the clinical trials in an efficient manner.
The FDA may take certain actions with respect to product candidates with such designations, including holding meetings with us throughout the development process, providing timely advice to us regarding development and approval, involving more senior staff in the review process, assigning a cross-disciplinary project lead for the review team, and taking other steps to provide guidance on the design of the clinical trials in an efficient manner.
Clinical trials typically are conducted in three sequential phases; however, the phases may overlap or may be combined. • Phase 1 clinical trials are initially conducted in a limited population of healthy humans or, for our product candidates, in patients, such as cancer patients, in order to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion, and pharmacodynamics, and to identify a recommended phase 2 dose. • Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications, and to determine dose tolerance and optimal dosage.
Clinical trials typically are conducted in three sequential phases. • Phase 1 clinical trials are initially conducted in a limited population of healthy humans or, for our product candidates, in patients, such as cancer patients, in order to test the product candidate for safety, including adverse effects, dose tolerance, absorption, metabolism, distribution, excretion, and pharmacodynamics, and to identify a recommended phase 2 dose. • Phase 2 clinical trials are generally conducted in a limited patient population to identify possible adverse effects and safety risks, evaluate the efficacy of the product candidate for specific targeted indications, and to determine dose tolerance and optimal dosage.
We believe that our novel Cas12a chRDNA genome-editing platform has broad potential applicability across human therapeutic indications, and our strategy is to demonstrate our platform’s capability by first developing improved allogeneic cell therapies in hematologic oncology indications.
We believe that our novel CRISPR-Cas12a chRDNA genome-editing platform has broad potential applicability across human therapeutic indications, and our strategy is to demonstrate our platform’s capability by first developing improved allogeneic cell therapies in hematologic oncology and autoimmune diseases.
We expect to rely on our CMOs for the manufacturing of our product candidates to expedite readiness for future clinical trials, and most of these CMOs have capabilities for commercial manufacturing.
We expect to rely on our CMOs for manufacturing our product candidates to expedite readiness for future clinical trials, and most of these CMOs have demonstrated capabilities for commercial manufacturing.
Within the FDA, the Center for Biologics Evaluation and Research (“CBER”) regulates gene therapy products. Within CBER, the review of gene therapy and related products is consolidated in the Office of Tissues and Advanced Therapies, and the FDA has established the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its reviews.
Within the FDA, the Center for Biologics Evaluation and Research (“CBER”) regulates gene therapy products. Within CBER, the review of gene therapy and related products is consolidated in the Office of Therapeutic Products, and the FDA has established the Cellular, Tissue and Gene Therapies Advisory Committee to advise CBER on its reviews.
The biopharmaceutical industry, and in particular the genome-editing and cell therapy fields, are characterized by intense investment and competition aimed at rapidly advancing new technologies.
The biopharmaceutical industry, in particular the cell therapy and genome editing fields, is characterized by intense investment and competition aimed at rapidly advancing new technologies.
As we continue to grow, we will find more opportunities to connect our teams, taking into account our different functions and 50 Table of Contents locations, while focusing on building a culture that is driven by our mission to develop innovative, transformative therapies through novel genome editing for patients with devastating diseases.
As we continue to grow, we will find more opportunities to connect our teams, taking into account our different functions and locations, while focusing on building a culture that is driven by our mission to develop innovative, transformative therapies through novel genome editing for patients with devastating diseases.
Our process development and manufacturing core competencies and advantages include: • a platform process that allows optimization and learnings across all of our product candidates and preclinical research programs; • internal process development to facilitate technical transfer to manufacturing sites; • readily available and established equipment that further enables the transfer from process development lab to cGMP operations; 33 Table of Contents • custom engineering and development to create the necessary specific requirements for our product candidates, while leveraging the broader platform to ensure robust processes; • removal of residual TCR positive T cells after genome editing to minimize the risk of GvHD in patients; • process understanding and cell manufacturing control for continuous optimization of productivity and product candidate quality; • closed manufacturing system; • highly specific development efforts focused on enhancing cell viability; • extensive core process knowledge of gene knockout, CAR expression, and gene insertion; • process control and optimization, allowing for increased retention of early memory T cell phenotypes; and • platform scale and efficiency to accommodate high dose yield per batch, with optimization for further commercial supply process.
Our process development and manufacturing core competencies and advantages include: • optimization and learnings across all of our product candidates and preclinical research programs, allowing for consistency and increased process robustness; • internal process development to facilitate optimization of manufacturing processes and technical transfers to manufacturing sites; • readily available and established equipment that further enables the transfer from our process development lab to cGMP operations; • custom engineering and development to create the necessary specific requirements for our product candidates, while leveraging the broader platform to ensure robust processes; • removal of residual TCR positive T cells after genome editing to minimize the risk of GvHD in patients; • process understanding and cell manufacturing control for continuous optimization of productivity and product candidate quality; • closed manufacturing systems; • highly specific development efforts focused on enhancing cell viability; • extensive core process knowledge of gene knockout, CAR expression, and gene insertion; • process control and optimization, allowing for increased retention of early memory T cell phenotypes; and • platform scale and efficiency to accommodate high dose yield per batch, with optimization for further commercial supply processes.
If we and such third party do not reach agreement on the Grant of Program Rights within a specified time period, Pfizer’s right of first negotiation will be reinstated. Under the Information Rights Agreement, we also agreed to grant Pfizer the right to designate one representative to serve on our SAB.
If we 16 Tabl e of Contents and such third party do not reach agreement on the Grant of Program Rights within a specified time period, Pfizer’s right of first negotiation will be reinstated. Under the Information Rights Agreement, we also agreed to grant Pfizer the right to designate one representative to serve on our SAB.
As consideration for the assignment, we made an upfront payment of $0.5 million and are obligated to pay all patent prosecution and maintenance costs going forward; up to $2.8 million in regulatory milestones for therapeutic products developed by us, our affiliates, and licensees; up to $20.0 million in sales milestones over a total of four therapeutics products sold by us, our affiliates, and licensees; and a percentage of sublicensing revenues received by us for licensing the chRDNA patent family.
As consideration for the assignment, we made an upfront payment of $0.5 million and are obligated to pay all patent prosecution and maintenance costs going forward; up to $2.8 million in regulatory milestones for therapeutic products, up to $20.0 million in sales milestones over a total of four therapeutics products, and a percentage of sublicensing revenues received by us for licensing the chRDNA patent family.
Treasury Department’s Office of Foreign Assets Controls could apply to any international activities we may undertake. Coverage, Pricing, and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we may seek regulatory approval by the FDA or other government authorities.
Treasury Department’s Office of Foreign Assets Controls could apply to any international activities we may undertake. 32 Tabl e of Contents Coverage, Pricing, and Reimbursement Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we may seek regulatory approval by the FDA or other government authorities.
A PTE cannot extend the remaining term of a patent 29 Table of Contents beyond a total of 14 years from the date of product approval and only one patent claiming the drug product, methods of use or methods of manufacturing may be restored.
A PTE cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval and only one patent claiming the drug product, methods of use, or methods of manufacturing may be restored.
Our chRDNA guides retain sufficiently high affinity to edit a genome at the intended location; however these guides have sufficiently low affinity for potential off-target sites to reduce the likelihood of a genome edit at an unintended location.
Our chRDNA guides retain high affinity to edit a genome at the intended location; however, these guides have lower affinity for potential off-target sites to reduce the likelihood of a genome edit at an unintended location.
CB-010 is being evaluated in our ANTLER phase 1 clinical trial in patients with r/r B-NHL, and CB-011 is being evaluated in our CaMMouflage phase 1 clinical trial in patients with r/r MM. CB-010 is directed to the CD19 antigen and CB-011 is directed to the BCMA antigen.
CB-010, directed to the CD19 antigen, is being evaluated in our ANTLER phase 1 clinical trial in patients with r/r B-NHL and our GALLOP phase 1 clinical trial in patients with LN and ERL. CB-011, directed to the BCMA antigen, is being evaluated in our CaMMouflage phase 1 clinical trial in patients with r/r MM.
The FDA may designate one or more of our product candidates for fast track review if our product candidate is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and it can be demonstrated that our product candidate has the potential to address unmet medical needs for such a disease or condition.
The FDA may designate one or more of our product candidates as a fast track product if our product candidate is intended, whether alone or in combination with one or more other products, for the treatment of a serious or life-threatening disease or condition, and it can be demonstrated that our product candidate has the potential to address an unmet medical need for such a disease or condition.
Our employees are our greatest asset, and we aim to create an equitable, inclusive, and collaborative environment with the overall goal of engaging our workforce to support our current pipeline, develop new technologies, and support future business goals, while protecting the long-term interests of our stockholders.
The Herd at Caribou Our employees are our greatest asset, and we aim to create an inclusive and collaborative environment with the overall goal of engaging our workforce to support our current pipeline, develop new technologies, and support future business goals, while protecting the long-term interests of our stockholders.
Patients in our AMpLify phase 1 clinical trial receive a chemotherapy regimen prior to CAR-T cell infusion. The chemotherapy regimen includes two agents, cyclophosphamide (750 mg/m 2 /day) and fludarabine (30 mg/m 2 /day) for three days. Patients then have two days of rest, following by a single CB-012 dose on Day 0.
Patients in our AMpLify phase 1 clinical trial receive a lymphodepletion regimen prior to CAR-T cell infusion. The lymphodepletion regimen includes two chemotherapy agents, cyclophosphamide (750 mg/m 2 /day) and fludarabine (30 mg/m 2 /day) for three days. Patients then have two days of rest, followed by a single CB-012 dose on day zero.
Additionally, we will owe Intellia low- to mid- single-digit percent royalties on net sales of our CB-010 product candidate by us, our affiliates, and sublicensees until the expiration, abandonment, or invalidation of the last patent within the intellectual property relating to CRISPR-Cas9, including that relating to Cas9 chRDNAs (i.e., 2036, without PTA or PTE).
Additionally, we will owe Intellia low- to mid- single-digit percent royalties on net sales of our CB-010 product candidate until the expiration, abandonment, or invalidation of the last patent within the intellectual property relating to CRISPR-Cas9, including that relating to Cas9 chRDNAs (i.e., 2036, without PTA or PTE).
If ProMab terminates the ProMab Agreement due to our uncured material breach or bankruptcy, we must cease the manufacture, use, and sale of any products or product candidates incorporating the purchased anti-BCMA scFv. Pioneer Hi-Bred International, Inc.
If ProMab terminates the ProMab Agreement due to our uncured material breach or bankruptcy, we must cease the manufacture, use, and sale of any products or product candidates incorporating the purchased anti-BCMA scFv. 17 Tabl e of Contents Pioneer Hi-Bred International, Inc.
Department of Justice (“DOJ”), or other governmental entities. 34 Table of Contents As we seek approval to market and distribute a new biologic in the United States, we generally must satisfactorily complete each of the following steps: • preclinical laboratory tests and formulation studies performed in accordance with the FDA’s current Good Laboratory Practice (“cGLP”) regulations; • manufacture and testing of clinical investigational product according to cGMPs; • submission to the FDA of an investigational new drug (“IND”) application for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent institutional review board (“IRB”), representing each clinical trial site before each clinical trial may be initiated, or by a central IRB if appropriate; • performance of adequate and well-controlled human clinical trials required to establish the safety and efficacy of the product candidate for each proposed indication, in accordance with the FDA’s current Good Clinical Practice (“cGCP”) regulations including, but not limited to, informed consent and investigator disclosure requirements; • preparation and submission to the FDA of a BLA for marketing approval of our product candidates for one or more proposed indications, including submission of detailed information on the manufacture and composition of our product candidates and proposed labeling; • review of the BLA by an FDA advisory committee, where applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of any third-party manufacturers, at which the product, or components thereof, are produced in order to assess compliance with cGMP requirements and to ensure that the facilities, methods, and controls are adequate to preserve and ensure the product’s identity, strength, quality, and purity, and, if applicable, the FDA’s current Good Tissue Practice (“cGTP”), for the use of human cell and tissue products; • satisfactory completion of any FDA audits of the nonclinical study and clinical trial sites to ensure compliance with cGLPs and cGCPs, respectively, and the integrity of nonclinical and clinical data in support of the BLA; • payment of user fees and securing FDA approval of the BLA; and • compliance with any post-approval requirements, including the potential requirement to implement Risk Evaluation and Mitigation Strategy (“REMS”), adverse event reporting, and compliance with any post-approval studies required or requested by the FDA.
As we seek approval to market and distribute a new biologic in the United States, we generally must satisfactorily complete each of the following steps: • nonclinical studies performed in accordance with the FDA’s current Good Laboratory Practice (“cGLP”) regulations; • manufacture and testing of clinical investigational product according to cGMPs; • submission to the FDA of an investigational new drug (“IND”) application for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent institutional review board (“IRB”), representing each clinical trial site before each clinical trial may be initiated, or by a central IRB if appropriate; • performance of adequate and well-controlled human clinical trials required to establish the safety and efficacy of the product candidate for each proposed indication, in accordance with the FDA’s current Good Clinical Practice (“cGCP”) regulations including, but not limited to, informed consent and investigator disclosure requirements; • preparation and submission to the FDA of a BLA seeking approval of our product candidates for one or more proposed indications, including submission of detailed information on the manufacture and composition of our product candidates and proposed labeling; 23 Tabl e of Contents • review of the BLA by an FDA advisory committee, where applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of any third-party manufacturers, at which the product, or components thereof, are produced in order to assess compliance with cGMP requirements and to ensure that the facilities, methods, and controls are adequate to preserve and ensure the product’s safety, purity, and potency, and, if applicable, the FDA’s current Good Tissue Practice (“cGTP”), for the use of human cell and tissue products; • satisfactory completion of any FDA audits of the nonclinical study and clinical trial sites to ensure compliance with cGLPs and cGCPs, respectively, and the integrity of nonclinical and clinical data in support of the BLA; • payment of user fees and securing FDA approval of the BLA; and • compliance with any post-approval requirements, including the potential requirement to implement Risk Evaluation and Mitigation Strategy (“REMS”), adverse event reporting, and compliance with any post-approval studies required or requested by the FDA.
A cell typically has two ways to repair the DSB, which results in the knockout of a gene or the insertion of new genetic material: non-homologous end joining (“NHEJ”) and homology-directed repair (“HDR”), respectively. NHEJ is an error-prone process in which the broken DNA ends are reattached.
A cell typically has two ways to repair the DSB, which results in the knockout of a gene or the insertion of new genetic material: non-homologous end joining (“NHEJ”) and homology-directed repair (“HDR”), respectively. NHEJ is an error-prone process in which the broken DNA ends are reattached. During NHEJ, the cell typically inserts or deletes nucleotides at the DSB.
We will be required to report certain adverse reactions and manufacturing problems to the FDA, provide updated safety and efficacy information, and comply with requirements concerning advertising and promotional labeling requirements.
We will be required to report certain adverse reactions and manufacturing problems to the FDA, provide updated safety and efficacy information, and comply with requirements concerning advertising and promotion.
Our platform and therapeutic product candidates are expected to face substantial competition from multiple technologies, marketed products, and numerous other therapies being developed by other biopharmaceutical companies, academic research institutions, governmental agencies, and private research institutions.
Our platform and therapeutic product candidates are expected to face substantial competition from multiple technologies, marketed products, and numerous other therapies being developed by other biopharmaceutical companies, larger and better funded pharmaceutical companies, academic research institutions, governmental agencies, and private research institutions.
Other CAR-T cell therapies that express endogenous PD-1 could become rapidly exhausted and lose antitumor activity due to the interaction between PD-1 and its ligand PD-L1. The PD-1/PD-L1 pathway leads to rapid exhaustion in T cells. This occurs when a T cell expressing PD-1 engages with another cell expressing PD-L1.
Other CAR-T cell therapies that express endogenous PD-1 could become rapidly exhausted and lose activity due to the interaction between PD-1 and its ligand PD-L1. PD-1/PD-L1 engagement leads to rapid exhaustion in T cells. This occurs when a T cell expressing PD-1 interacts with another cell expressing PD-L1.
These requirements include submissions of safety and other post-marketing information and reports, including mandatory post-marketing safety reporting; registration and listing requirements; cGMP requirements relating to quality control, quality assurance, and corresponding maintenance of records and documents; and requirements regarding recordkeeping.
These requirements include submissions of safety and other post-marketing information and reports, including mandatory post- 31 Tabl e of Contents marketing safety reporting; registration and listing requirements; cGMP requirements relating to quality control, quality assurance, and corresponding maintenance of records and documents; and requirements regarding recordkeeping.
Five-year survival in these patients is Intensive induction chemotherapy, known as 7 + 3, consisting of cytarabine and an anthracycline is the most effective therapy for adults newly diagnosed with AML, although the treatment has significant associated toxicities. Thus, there remains significant unmet need in the treatment of patients with AML.
Intensive induction chemotherapy, known as 7 + 3, consisting of cytarabine and an anthracycline, is the most effective therapy for adults newly diagnosed with AML, although the treatment has significant associated toxicities. There remains significant unmet need in the treatment of patients with AML.
Our AMpLify clinical trial includes patients who have not responded to or relapsed after standard treatment and excludes patients who have been treated with more than three prior lines of therapy and patients with proliferative disease. Patients with prior allogeneic or autologous cell therapies are allowed to participate in our AMpLify clinical trial.
Our AMpLify clinical trial includes patients who have not responded to or relapsed after standard treatment and excludes patients who have been treated with more than three prior lines of therapy and patients with proliferative disease. Patients who received prior allogeneic stem cell transplant are allowed to participate in our AMpLify clinical trial.
Our common stock price will be determined by reference to the 45-day volume weighted-average trading price of our common stock. At our option, payments may be made in cash or common stock.
Our common stock price will be determined by reference to the 45-trading day volume weighted-average trading price of our common stock immediately preceding the date of determination. At our option, payments may be made in cash or common stock.
The sublicensing agreements that we entered into prior to December 18, 2020 (for example, the Intellia Agreement discussed below) are not subject to these economics. 27 Table of Contents Intellia Therapeutics, Inc.
The sublicensing agreements that we entered into prior to December 18, 2020 (for example, the Intellia Agreement discussed below) are not subject to these economics. Intellia Therapeutics, Inc.
To our knowledge, our CB-010 product candidate is the first allogeneic CAR-T cell therapy in a clinical study with a PD-1 knockout, and we believe the PD-1 knockout enhances the potential for durable antitumor response of an allogeneic CAR-T cell therapy.
To our knowledge, our CB-010 product candidate is the first allogeneic CAR-T cell therapy in a clinical trial with a PD-1 knockout, and we believe the PD-1 knockout enhances the potential for durable activity of an allogeneic CAR-T cell therapy.
In addition, the government may assert that a 45 Table of Contents claim including items and services resulting from a violation of the AKS or FDA promotional standards constitutes a false or fraudulent claim for purposes of the U.S.
In addition, the government may assert that a claim including items and services resulting from a violation of the AKS or FDA promotional standards constitutes a false or fraudulent claim for purposes of the U.S. False Claims Act; • the U.S.
Anti-corruption laws generally prohibit companies and their employees, agents, contractors, and other collaborators from authorizing, promising, offering, or providing, directly or indirectly, improper payments or anything else of value to recipients in the public or private sector in order to influence action.
Anti-corruption laws generally prohibit companies and their employees and certain other third parties from authorizing, promising, offering, or providing, directly or indirectly, improper payments or anything else of value to recipients in the public or private sector in order to influence action.
The phase 2 clinical trial for our product candidates may serve as the pivotal phase 3 trial, in which case a separate phase 3 clinical trial will not be necessary. • Phase 3 clinical trials are undertaken within an expanded patient population to further evaluate dosage and gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling.
In appropriate circumstances, a phase 2 clinical trial may serve as the basis for an application, in which case a separate phase 3 clinical trial will not be necessary. • Phase 3 clinical trials are undertaken within an expanded patient population to gather the additional information about effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the drug and to provide an adequate basis for physician labeling.
Canonical genome editing occurs in two steps, as shown in figure 2 below. In the first step, a double-stranded break (“DSB”) is made at the location of the genome where the edit is desired.
Genome editing can occur in two steps, as shown in the figure below. In the first step, a double-stranded break (“DSB”) is made at the location of the genome where the edit is desired.
Such laws may not only affect coverage, reimbursement, and pricing for our product candidates, but can also result in civil penalties for late or incorrect reports; • U.S. consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • the FCPA, which prohibits companies and their intermediaries from making, or offering or promising to make, improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; • certain state and other laws that require pharmaceutical companies to comply with the state standards or pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. government in addition to requiring pharmaceutical manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures; • certain state and other laws that govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts; and • analogous state and foreign laws and regulations, which may be broader in scope than their federal equivalents. 46 Table of Contents Numerous federal and state laws and regulations, including federal health information privacy laws, state data breach notification laws, state health information privacy laws and federal and state consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), that govern the collection, use, disclosure, and protection of health-related and other personal information could apply to our operations or the operations of our collaborators and third-party providers.
Such laws may not only affect coverage, reimbursement, and pricing for our product candidates, but can also result in civil penalties for late or incorrect reports; • U.S. consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • the FCPA, which prohibits companies and their intermediaries from making, or offering or promising to make, improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; • certain state and other laws that require pharmaceutical companies to comply with the state standards or pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the U.S. government in addition to requiring pharmaceutical manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures; • certain state and other laws that govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts; and • analogous state and foreign laws and regulations, which may be broader in scope than their federal equivalents.
CB-011 Overview: Strategy and Rationale CB-011 is a healthy donor-derived, genome-edited, allogeneic CAR-T cell therapy targeting BCMA-positive malignancies that is being evaluated in the ongoing open-label, multicenter CaMMouflage phase 1 clinical trial (NCT05722418) in the United States in adults with r/r MM.
CB-011 Overview: Strategy and Rationale CB-011 is an allogeneic CAR-T cell therapy targeting BCMA-positive malignancies that is being evaluated in our ongoing open-label, multicenter CaMMouflage phase 1 clinical trial (NCT05722418) in the United States in adults with r/r MM.
(“Pfizer”), pursuant to which we, in a private placement transaction, sold to Pfizer 4,690,431 shares of our common stock, par value $0.0001 per share, at a purchase price of $5.33 per share, for aggregate gross proceeds of approximately $25.0 million (“Pfizer Investment”).
(“Pfizer”), pursuant to which we, in a private placement transaction, sold to Pfizer 4,690,431 shares of our common stock, par value $0.0001 per share, at a purchase price of $5.33 per share, for aggregate gross proceeds of approximately $25.0 million (“Pfizer Investment”). The issuance and sale of the shares to Pfizer closed on June 30, 2023.
We believe that knocking out PD-1 will maintain the CAR-T cells in a higher antitumor state for an extended period of time, which we believe will result in greater initial tumor debulking in the patient, thereby enabling a potentially better therapeutic index relative to PD-1-expressing CAR-T cells.
We believe that knocking out PD-1 will maintain the CAR-T cells in an enhanced activity state for an extended period of time, which we believe will result in greater activity against disease in the patient, thereby enabling a potentially better therapeutic index relative to PD-1-expressing CAR-T cells.
Under the terms of the ProMab Agreement, in the event we, or our affiliates or licensees, receive regulatory approval for CB-011, we will owe ProMab low-single-digit percent royalties on net sales by us, our affiliates, and licensees until the expiration, abandonment, or invalidation of the last patent within the assigned patent family (i.e., 2040 for U.S. patents, without patent term adjustment (“PTA”) or patent term extension (“PTE”)).
Under the terms of the ProMab Agreement, in the event that CB-011 is approved by the FDA, we will owe ProMab low-single-digit percent royalties on net sales until the expiration, abandonment, or invalidation of the last patent within the assigned patent family (i.e., 2040 for U.S. patents, without patent term adjustment (“PTA”) or patent term extension (“PTE”)).
The materials we file with or furnish to the SEC are also available at http://www.sec.gov. 51 Table of Contents
The materials we file with or furnish to the SEC are also available at http://www.sec.gov. 38 Tabl e of Contents
The median age of diagnosis is 69 years, and there were an estimated 35,730 new cases in 2023 in the United States with an estimated 12,590 deaths in 2023. Five-year survival in these patients is approximately 58%.
The median age of diagnosis is 69 years, and there were an estimated 35,780 new cases in 2024 in the United States with an estimated 12,540 deaths in 2024. Five-year survival in these patients is approximately 61%.
We evaluated the integrity and performance of chRDNA guides by employing two unique assays, the SITE-Seq® assay and the VINE assay, on two genes known from the scientific literature to suffer from high rates of off-target editing with either the Cas9 or Cas12a protein. As seen in figure 3 above, all-RNA guides generated both robust on-target and off-target editing.
We 6 Tabl e of Contents evaluated the integrity and performance of chRDNA guides by employing two unique assays, the SITE-Seq® assay and the VINE assay, on two genes known from the scientific literature to exhibit high rates of off-target editing with either the Cas9 or Cas12a protein and all-RNA guides. All-RNA guides generated both robust on-target and off-target editing.
To ensure optimal engraftment of the allogeneic CB-010 cells, we use a more intensive regimen of these chemotherapeutic agents than is used with the commercially approved autologous CAR-T cell therapies, namely cyclophosphamide at 60 mg/kg/day for 2 days, then fludarabine at 25 mg/m 2 /day for 5 days.
To ensure optimal engraftment of the allogeneic CB-010 cells, we use a deeper regimen of these chemotherapeutic agents, i.e., cyclophosphamide at 60 mg/kg/day for two days and then fludarabine at 25 mg/m 2 /day for five days, than is used with the commercially available autologous CAR-T cell therapies.
If we receive a complete response letter, we may submit to the FDA information that represents a complete response to the issues identified by the FDA. Such resubmissions are classified under the PDUFA as either class 1 or class 2. The classification of a resubmission is based on the information submitted by us in response to the complete response letter.
If we receive a complete response letter, we may submit to the FDA information that represents a complete response to the issues identified by the FDA. Such resubmissions are classified under the PDUFA as either class 1 or class 2.
B cell tumors and the patient’s own cells can express PD-L1, leading to interaction with PD-1 and subsequent exhaustion of the CAR-T cells. We eliminate PD-1 expression from the CB-010 CAR-T cells, thereby preventing PD-1/PD-L1-mediated exhaustion. More than half of B-NHL tumors express PD-L1, and expression of PD-L1 in B-NHL correlates with poorer outcomes.
B cell tumors and the patient’s own cells express PD-L1, leading to interaction with PD-1 and subsequent exhaustion of the CAR-T cells. We prevent PD-1 expression on the CB-010 CAR-T cells, thereby disrupting PD-1/PD-L1-mediated exhaustion. More than half of B-NHL tumors express PD-L1, correlating with poorer outcomes.
However, the FDA’s time period goal for reviewing a fast track application does not begin until the last section of the application is submitted.
However, the FDA’s goal for reviewing a rolling submission does not begin until the last section of the application is submitted.
Our chRDNA technologies enable us to design allogeneic cell therapies with the potential to achieve enhanced cell killing activity through the use of tailored armoring strategies, including (i) checkpoint disruption, such as through a knockout of PD-1 to sustain the initial activity of CAR-T cells by disrupting a pathway that leads to CAR-T cell exhaustion; (ii) immune cloaking of CAR-T cells to reduce rejection by the patient’s immune system; (iii) cytokine support to enhance antitumor activity; and (iv) a combination of these strategies. • Developing allogeneic CAR-T cell therapies against clinically proven targets for the treatment of hematologic malignancies.
Our chRDNA technologies enable us to design allogeneic cell therapies with the potential to achieve enhanced activity against diseased cells through the use of armoring strategies, including (i) checkpoint disruption, such as through a knockout of PD-1 to sustain the activity of CAR-T cells by disrupting a pathway that leads to CAR-T cell exhaustion; (ii) immune cloaking of CAR-T cells to reduce rejection by the lymphoid compartment of a patient’s immune system; and (iii) a combination of these strategies. • Developing allogeneic CAR-T cell therapies against clinically validated targets to derisk our clinical programs.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeWe 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 65 Table of Contents associated with orphan drug designation, including market exclusivity, which may cause our revenue, if any, to be reduced.
Biggest changeHowever, 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. 53 Tabl e of Contents We may continue to seek orphan drug designation for our allogeneic CAR-T 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.
We may never be able to develop or commercialize a marketable cell therapy product. We are early in our development efforts. All of our programs will require clinical development, regulatory approval, manufacturing at commercial scale, distribution channels, a commercial organization, significant marketing efforts, and substantial investment before we generate any revenue from product sales.
We may never be able to develop or commercialize a marketable cell therapy product. We are early in our product development efforts. All of our programs will require clinical development, regulatory approval, manufacturing at commercial scale, distribution channels, a commercial organization, significant marketing efforts, and substantial investment before we generate any revenue from product sales.
Risks Relating to Our Business, Government Regulation, Technology, and Industry We are early in our development efforts and it will be many years before we commercialize a product candidate, if ever.
Risks Relating to our Business, Government Regulation, Technology, and Industry We are early in our product development efforts and it will be many years before we commercialize a product candidate, if ever.
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 . The manufacturing processes used to produce our cell therapy product candidates are and will be complex, as our product candidates are new products.
Manufacturing 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. The manufacturing processes used to produce our cell therapy product candidates are and will be complex, as our product candidates are new products.
The motions phase of this interference has concluded and the priority phase suspended until the CAFC appeal is decided.
The motions phase of this interference has concluded, and the priority phase is suspended until the CAFC appeal is decided.
Risks Relating to Our Relationships with Third Parties We rely on third parties to supply the materials for, and the manufacturing of, our clinical product candidates, and, if such product candidates receive regulatory approval, we may continue our reliance on third parties for manufacturing of our commercial products. Our continued success is subject to the performance of these third parties.
Risks Relating to our Relationships with Third Parties We rely on third parties to supply the materials for, and the manufacturing of, our clinical product candidates, and, if such product candidates receive regulatory approval, we may continue our reliance on third parties for manufacturing our commercial products. Our continued success is subject to the performance of these third parties.
Thus, even if we obtain patent protection on certain aspects of our technologies, such protection may not be enough to block our competitors from entering the market. Third-party claims of intellectual property infringement may prevent or delay our ability to commercialize our product candidates. The fields of genome editing and CAR-T and CAR-NK cell therapies are relatively new.
Thus, even if we obtain patent protection on certain aspects of our technologies, such protection may not be enough to block our competitors from entering the market. Third-party claims of intellectual property infringement may prevent or delay our ability to commercialize our product candidates. The fields of CAR-T cell therapies and genome editing are relatively new.
Even with the requisite approvals from the FDA and other regulatory authorities internationally, the commercial success of our product candidates will depend, in significant part, on the acceptance of physicians, patients, and healthcare payors of products generated through genome editing in general, and our allogeneic CAR-T and CAR-NK cell therapy product candidates in particular, as medically necessary, cost-effective, safe, and effective therapies.
Even with the requisite approvals from the FDA and other regulatory authorities internationally, the commercial success of our product candidates will depend, in significant part, on the acceptance of physicians, patients, and healthcare payors of products generated through genome editing in general, and our allogeneic CAR-T cell therapy product candidates in particular, as medically necessary, cost-effective, safe, and effective therapies.
Furthermore, we will continue to incur costs associated with operating as a public company, including significant legal, accounting, insurance, investor relations, and other expenses. Additionally, the rapidly evolving nature of the genome-editing and cell therapy fields may make it difficult to evaluate our technologies and product candidates as well as to predict our future performance.
Furthermore, we will continue to incur costs associated with operating as a public company, including legal, accounting, insurance, investor relations, and other expenses. Additionally, the rapidly evolving nature of the genome-editing and cell therapy fields may make it difficult to evaluate our technologies and product candidates as well as to predict our future performance.
In addition, approved autologous CAR-T therapies and those under development have shown frequent rates of cytokine release syndrome, neurotoxicity, serious infections, prolonged cytopenia, hypogammaglobulinemia, and other SAEs that have resulted in patient death. There may be similar adverse events for our allogeneic CAR-T and CAR-NK cell therapy product candidates, including patient death.
In addition, approved autologous CAR-T therapies and those under development have shown frequent rates of cytokine release syndrome, neurotoxicity, serious infections, prolonged cytopenia, hypogammaglobulinemia, and other SAEs that have resulted in patient death. There may be similar adverse events for our allogeneic CAR-T cell therapy product candidates, including patient death.
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. 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.
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 harmed. 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.
We have limited financial and managerial resources. We are focused initially on allogeneic CAR-T and CAR-NK cell therapies and, as a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential.
We have limited financial and managerial resources. We are focused initially on allogeneic CAR-T cell therapies and, as a result, we may forego or delay pursuit of opportunities with other product candidates or for other indications that later prove to have greater commercial potential.
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.
We may also request regulatory approval of future CAR-T 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.
The success of our product candidates will depend on several factors, including the following: • sufficiency of our financial and other resources; • acceptance of our chRDNA genome-editing technology; • ability to develop and deploy armoring technologies so that our product candidates have a competitive edge; • successful completion of preclinical studies; • clearance of IND applications to initiate clinical trials; • successful enrollment in, and completion of, our clinical trials; • data from our clinical trials that support an acceptable risk-benefit profile of our product candidates for our intended patient populations and indications and demonstrate safety and efficacy; • establishment of agreements with CMOs for clinical and commercial supplies and scaling up of manufacturing processes and capabilities to support our clinical trials; • successful development of our internal process development and transfer to larger-scale facilities; • receipt of regulatory and marketing approvals from applicable regulatory authorities as well as receipt of regulatory exclusivity for our product candidates; • establishment, maintenance, enforcement, and defense of patent and trade secret protection and other intellectual property rights; • not infringing, misappropriating, or otherwise violating third-party intellectual property rights; • entry into collaborations to further the development of our product candidates or for the development of new product candidates; • establishment of sales, marketing, and distribution capabilities for commercialization of our product candidates if and when approved, whether by us or in collaboration with third parties; • identification and establishment of a stable supply chain that permits us to procure the necessary materials for our product candidates; • 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; 56 Table of Contents • 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; • 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; and • expanding indications and patient populations for our products post-approval.
The success of our product candidates will depend on several factors, including the following: • sufficiency of our financial and other resources; • acceptance of our chRDNA genome-editing technology; • ability to develop and deploy armoring technologies so that our product candidates have a competitive edge; • successful completion of preclinical studies; • clearance of IND applications to initiate clinical trials; • successful enrollment in, and completion of, our clinical trials; • data from our clinical trials that support an acceptable risk-benefit profile of our product candidates for our intended patient populations and indications and demonstrate safety and efficacy; • establishment of agreements with CMOs for clinical and commercial supplies and scaling up of manufacturing processes and capabilities to support our clinical trials; • successful development of our internal process development and transfer to larger-scale facilities; • receipt of regulatory and marketing approvals from applicable regulatory authorities as well as receipt of regulatory exclusivity for our product candidates; • establishment, maintenance, enforcement, and defense of patent and trade secret protection and other intellectual property rights; • not infringing, misappropriating, or otherwise violating third-party intellectual property rights; • entry into collaborations to further the development of our product candidates or for the development of new product candidates; • establishment of sales, marketing, and distribution capabilities for commercialization of our product candidates if and when approved, whether by us or in collaboration with third parties; • identification and establishment of a stable supply chain that permits us to procure the necessary materials for our product candidates; • 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; 43 Tabl e of Contents • 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; • 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; and • expanding indications and patient populations for our products post-approval.
We are not currently classified as a covered entity or business associate under HIPAA and thus are not subject to its requirements or penalties. However, any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles.
We are not currently classified as a covered entity or business associate under HIPAA and thus are not subject to its requirements or penalties. Any person may be prosecuted under HIPAA’s criminal provisions either directly or under aiding-and-abetting or conspiracy principles.
Even if we are able to enter into a collaboration, the following are some of the risks associated with doing so: • collaborators have significant discretion in determining the efforts and resources that they will apply to collaborations and may not devote sufficient resources to the development, manufacturing, marketing, or sale of collaboration products; • collaborators may not pursue development and commercialization of any product candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding, or external factors such as an acquisition that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials, or require further development of a product candidate for clinical testing; • collaborators may adopt alternative technologies, which could decrease the marketability of our product candidates and genome-editing technologies; • collaborators may independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours, that may result in the withdrawal of the collaborator support for our collaboration product candidates; • collaborators with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of our product candidates; • collaborators may not properly obtain, maintain, enforce, or defend our intellectual property if we grant such rights or may use our intellectual property in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or expose us to potential litigation; • we may lose certain valuable rights under circumstances identified in our collaborations, including if we undergo a change in control; 90 Table of Contents • 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; • collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner, if at all.
Even if we are able to enter into a collaboration, the following are some of the risks associated with doing so: • collaborators have significant discretion in determining the efforts and resources that they will apply to collaborations and may not devote sufficient resources to the development, manufacturing, marketing, or sale of collaboration products; • collaborators may not pursue development and commercialization of any product candidates we may develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding, or external factors such as an acquisition that diverts resources or creates competing priorities; • collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials, or require further development of a product candidate for clinical testing; • collaborators may adopt alternative technologies, which could decrease the marketability of our product candidates and genome-editing technologies; • collaborators may independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours, that may result in the withdrawal of the collaborator support for our collaboration product candidates; • collaborators with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of our product candidates; • collaborators may not properly obtain, maintain, enforce, or defend our intellectual property if we grant such rights or may use our intellectual property in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or expose us to potential litigation; 79 Tabl e of Contents • we may lose certain valuable rights under circumstances identified in our collaborations, including if we undergo a change in control; • 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; • collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner, if at all.
This exclusive forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, executive officers, or other employees, which may discourage lawsuits against us and our directors, executive officers, and other employees.
This exclusive federal forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, executive officers, or other employees, which may discourage lawsuits against us and our directors, executive officers, and other employees.
We expect the innovative nature of our product candidates to create further challenges in obtaining regulatory approval. For example, the FDA has limited experience with the development of allogeneic T cell and NK cell therapies for cancer and other diseases.
We expect the innovative nature of our product candidates to create further challenges in obtaining regulatory approval. For example, the FDA has limited experience with the development of allogeneic T cell cell therapies for cancer and other diseases.
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.
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 third parties have intellectual property relating to RNA-guided Cas9 genome editing.
Although the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive forum provisions.
Although the Delaware courts have determined that such choice of forum provisions are facially valid, a stockholder may nevertheless seek to bring a claim in a venue other than those designated in the exclusive federal forum provisions.
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.
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 development, expand our research and development activities, develop new product candidates, initiate and complete clinical trials, seek regulatory approval and, if we receive approval from the FDA or foreign regulatory authorities, commercialize our products.
Our failure to meet the continued listing requirements of Nasdaq could result in a delisting of our common stock. Our common stock is currently listed on the Nasdaq Global Select Market.
Our failure to meet the continued listing requirements of Nasdaq could result in the delisting of our common stock. Our common stock is currently listed on the Nasdaq Global Select Market.
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. Ethical, social, and legal concerns about genome editing could result in the development of additional regulations restricting or prohibiting our products.
The use of CAR-T 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. Ethical, social, and legal concerns about genome editing could result in the development of additional regulations restricting or prohibiting our products.
All of our employees are “at will,” which means that any of our employees could leave our employment at any time, with or without notice. We conduct substantially all of our research activities at our facilities in Berkeley, California. The San Francisco Bay Area is headquarters to many other biopharmaceutical companies and many academic and research institutions.
All our non-officer employees are “at will,” which means that any of our employees could leave our employment at any time, with or without notice. We conduct substantially all our research activities at our facilities in Berkeley, California. The San Francisco Bay Area is headquarters to many other biopharmaceutical companies and many academic and research institutions.
Disputes may arise with the third parties from whom we license or take assignment of our intellectual property rights from for a variety of reasons, including: • the scope of rights granted under the license or assignment agreement and other interpretation-related issues; 82 Table of Contents • the extent to which our technology and processes infringe on, or derive from, intellectual property of the licensor that is not subject to the license or assignment agreement and is not covered by a covenant not to sue; • the sublicensing of rights and the obligations to our licensors associated with sublicensing; • our diligence obligations under license or assignment agreements and what activities satisfy those diligence obligations; and • whether payments are due and when.
Disputes may arise with the third parties from whom we license or take assignment of our intellectual property rights from for a variety of reasons, including: • the scope of rights granted under the license or assignment agreement and other interpretation-related issues; • the extent to which our technology and processes infringe on, or derive from, intellectual property of the licensor that is not subject to the license or assignment agreement and is not covered by a covenant not to sue; • the sublicensing of rights and the obligations to our licensors associated with sublicensing; • our diligence obligations under license or assignment agreements and what activities satisfy those diligence obligations; and • whether payments are due and when.
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; (iii) the results of these 61 Table of Contents trials, studies, or tests are negative or produce inconclusive results; (iv) there are safety concerns; or (v) we determine that the observed safety or efficacy profile would not be competitive in the marketplace, we may: • abandon the development of one or more product candidates; • incur unplanned costs; • be delayed in obtaining marketing approval for our product candidates or not obtain marketing approval at all; • obtain marketing approval in some jurisdictions and not in others; • obtain marketing approval for indications or patient populations that are not as broad as we intended or designed; • obtain marketing approval with labeling that includes significant use restrictions or safety warnings, including black box warnings; • be subject to additional post-marketing requirements; or • have regulatory agencies remove the product from the market or we voluntarily withdraw the product from the market after obtaining marketing approval.
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; (iii) the results of these 48 Tabl e of Contents trials, studies, or tests are negative or produce inconclusive results; (iv) there are safety concerns; or (v) we determine that the observed safety or efficacy profile would not be competitive in the marketplace, we may: • abandon the development of one or more product candidates; • incur unplanned costs; • be delayed in obtaining marketing approval for our product candidates or not obtain marketing approval at all; • obtain marketing approval in some jurisdictions and not in others; • obtain marketing approval for indications or patient populations that are not as broad as we intended or designed; • obtain marketing approval with labeling that includes significant use restrictions or safety warnings, including black box warnings; • be subject to additional post-marketing requirements; or • have regulatory agencies remove the product from the market or we voluntarily withdraw the product from the market after obtaining marketing approval.
Because we are developing CAR-T and CAR-NK cell therapy product candidates that are unique biological entities, the regulatory requirements to which we will be subject are not entirely clear. Even with respect to more established products that fit into the categories of gene therapies or cell therapies, the regulatory landscape is still developing.
Because we are developing CAR-T cell therapy product candidates that are unique biological entities, the regulatory requirements to which we will be subject are not entirely clear. Even with respect to more established products that fit into the categories of gene therapies or cell therapies, the regulatory landscape is still developing.
We have experienced prior ownership changes in 2014, 2016, and most recently in July 2021 upon our IPO. We do not expect any permanent limitations on our tax attributes. We have recorded a full valuation allowance for deferred tax assets, including NOLs and tax credits as of December 31, 2023.
We have experienced prior ownership changes in 2014, 2016, and most recently in July 2021 upon our IPO. We do not expect any permanent limitations on our tax attributes. We have recorded a full valuation allowance for deferred tax assets, including NOLs and tax credits as of December 31, 2024.
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.
A severe or prolonged economic downturn, including as a result of pandemics or other public health crises, the ongoing war between Russia and Ukraine, conflict in the Middle East, and tension between China and Taiwan, 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.
If we encounter safety or efficacy problems in our ongoing or future studies, our developmental plans and business could be significantly harmed. Product candidates in later stages of clinical trials may fail to show the desired safety profiles and efficacy results despite having progressed through initial clinical trials.
If we encounter safety or efficacy problems in our ongoing or future studies, our developmental plans and business could be materially harmed. Product candidates in later stages of clinical trials may fail to show the desired safety profiles and efficacy results despite having progressed through initial clinical trials.
Factors that may inhibit our efforts to commercialize our products on our own include: • our inability to recruit, hire, train, and retain adequate numbers of effective sales, marketing, customer service, medical affairs, and other support personnel; • our inability to equip sales personnel with effective materials, including sales literature, to help them educate physicians and other healthcare providers regarding our product candidates and their approved indications; • our inability to effectively manage a geographically dispersed sales and marketing team; • the inability of medical affairs personnel to negotiate arrangements for reimbursement and other acceptance by payors; • the inability to price our products at a sufficient price point to ensure an adequate and attractive level of profitability; and • unforeseen costs and expenses associated with creating an independent sales and marketing organization.
Factors that may inhibit our efforts to commercialize our products on our own include: • our inability to recruit, hire, train, and retain adequate numbers of effective sales, marketing, customer service, medical affairs, and other support personnel; • our inability to equip sales personnel with effective materials, including sales literature, to help them educate physicians and other healthcare providers regarding our product candidates and their approved indications; • our inability to effectively manage a geographically dispersed sales and marketing team; • the inability of medical affairs personnel to negotiate arrangements for reimbursement and other acceptance by payors; 57 Tabl e of Contents • the inability to price our products at a sufficient price point to ensure an adequate and attractive level of profitability; and • unforeseen costs and expenses associated with creating an independent sales and marketing organization.
The GDPR also permits 75 Table of Contents 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.
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.
Moreover, if disputes over intellectual property that we have licensed, or taken assignment of, prevent or impair our ability 81 Table of Contents 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.
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.
We may not receive additional priority review, such as RMAT designation, breakthrough therapy designation, or fast track designation, by the FDA for our allogeneic CAR-T and CAR-NK cell therapies. We may continue to apply for certain expedited programs in the United States, such as RMAT, breakthrough therapy, fast track, or priority review programs.
We may not receive additional priority review, such as RMAT designation, breakthrough therapy designation, or fast track designation, by the FDA for our allogeneic CAR-T cell therapies. We may continue to apply for certain expedited programs in the United States, such as RMAT, breakthrough therapy, fast track, or priority review programs.
The USPTO requires compliance with a number of procedural, documentary, fee payment, and other similar provisions during the patent application process. 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.
The USPTO requires compliance with various procedural, documentary, fee payment, and other similar provisions during the patent application process. 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.
Current and future growth imposes significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining, motivating, and integrating additional employees; 92 Table of Contents • 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; and • improving our operational, financial and management controls, reporting systems, and procedures.
Current and future growth imposes significant added responsibilities on members of management, including: • identifying, recruiting, integrating, maintaining, motivating, and integrating additional employees; • 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; and • improving our operational, financial and management controls, reporting systems, and procedures.
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.
We may submit applications to FDA for additional orphan drug designation for our allogeneic CAR-T cell therapy product candidates in specific orphan indications in which there is a medically plausible basis for the use of these products.
The biopharmaceutical industry, and the genome-editing, cell therapy, and immuno-oncology industries specifically, is characterized by intense competition and rapid innovation. Our potential competitors include major multi-national pharmaceutical companies, established biotechnology companies, specialty pharmaceutical companies, and universities and other research institutions.
The biopharmaceutical industry, and the cell therapy and genome editing industries specifically, is characterized by intense competition and rapid innovation. Our potential competitors include major multi-national pharmaceutical companies, established biotechnology companies, specialty pharmaceutical companies, and universities and other research institutions.
This could have a corresponding effect on our business, including putting us in breach of our obligations under privacy laws and regulations as discussed above, which could in turn adversely affect our business, financial condition, results of operations, and prospects.
This could have a corresponding effect on our business, including putting us in breach of our obligations under federal and state privacy laws and regulations as discussed above, which could in turn adversely affect our business, financial condition, results of operations, and prospects.
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 86 Table of Contents 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.
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.
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.
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 and biologic development activities, which could affect their performance on our behalf.
In addition, later discovery of previously unknown problems with our products or the manufacturing of our products, may cause: • restrictions on our products or the manufacturing of our products; • restrictions on the labeling or marketing of our products; • restrictions on the exportation, distribution, or use of our products; • requirements to conduct post-marketing clinical trials; • receipt of warning or untitled letters; • withdrawal of our products from the market; • refusal to approve pending BLAs or BLA supplements that we submit; • recall of our products; • fines, restitution, or disgorgement of profits or revenue; • suspension or withdrawal of marketing approvals; • suspension of any ongoing clinical trials; • product seizure; and • injunctions or the imposition of civil or criminal penalties.
In addition, later discovery of previously unknown problems with our products or the manufacturing of our products, may cause: • restrictions on our products or the manufacturing of our products; • restrictions on the labeling or marketing of our products; • restrictions on the exportation, distribution, or use of our products; • requirements to conduct post-marketing clinical trials; • receipt of warning or untitled letters; • withdrawal of our products from the market; • refusal to approve pending BLAs or BLA supplements that we submit; • recall of our products; • fines, restitution, or disgorgement of profits or revenue; • suspension or withdrawal of marketing approvals; • suspension of any ongoing clinical trials; • product seizure; and 55 Tabl e of Contents • injunctions or the imposition of civil or criminal penalties.
If any of the physicians or other providers or 73 Table of Contents 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.
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 criminal, civil, or administrative sanctions, including exclusions from government-funded healthcare programs and imprisonment, which could affect our ability to operate our business.
Our future capital requirements will depend on, and could increase significantly as a result of, many factors, including: • costs, progress, and results of our product candidate preclinical studies and clinical trials; • 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; • 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; • expansion of our workforce or our facilities; • costs of establishing and maintaining a supply chain for the development and manufacture of our product candidates; • timing and outcome of regulatory review of our product candidates; • our ability to establish and maintain collaborations on favorable terms; 53 Table of Contents • 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; • achievement of milestones that trigger payments under any of our current license and assignment agreements as well as under any additional agreements we enter into in the future; • costs of preparing, filing, prosecuting, and maintaining our patent portfolio, including costs associated with administrative proceedings of patent offices; • litigation costs in the event we seek to enforce our patents against third parties or if we are sued for infringement by third parties as well as for stockholder lawsuits; • effects of competing technologies, success or failure of products similar to our product candidates, and market developments; • costs of establishing or contracting for sales and marketing capabilities if we obtain regulatory approvals to market our product candidates; and • costs of operating as a public company.
Our future capital requirements will depend on, and could increase significantly as a result of, many factors, including: • costs, progress, and results of our product candidate preclinical studies and clinical trials; • 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 or regulatory environment or pandemics or other public health crises; • 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; • expansion of our workforce or our facilities; • costs of establishing and maintaining a supply chain for the development and manufacture of our product candidates; • timing and outcome of regulatory review of our product candidates; • our ability to establish and maintain collaborations on favorable terms; 40 Tabl e of Contents • 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; • achievement of milestones that trigger payments under any of our current license and assignment agreements as well as under any additional agreements we enter into in the future; • costs of preparing, filing, prosecuting, and maintaining our patent portfolio, including costs associated with administrative proceedings of patent offices; • litigation costs in the event we seek to enforce our patents against third parties or if we are sued for infringement by third parties as well as for securities lawsuits; • effects of competing technologies, success or failure of products similar to our product candidates, and market developments; • costs of establishing or contracting for sales and marketing capabilities if we obtain regulatory approvals to market our product candidates; and • costs of operating as a public company, including defending against any class action securities litigation.
If we have difficulty enrolling a sufficient number of patients to conduct our clinical trials as planned, we may need to delay, limit, or 60 Table of Contents 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.
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 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.
As a result, investors seeking cash dividends should not invest in our common stock. 102 Table of Contents 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.
As a result, investors seeking cash dividends should not invest in our common stock. 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.
All these factors could be costly to us and otherwise harm our business, financial condition, results of operations, and prospects. 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.
All these factors could be costly to us and otherwise harm our business, financial condition, results of operations, and prospects. Our business is highly dependent on the success of our product candidates, which will require significant additional human clinical trials before we can seek regulatory approval and potentially commercialize our product candidates.
A REMS could include medication guides, physician communication plans, or other elements to ensure safe use, such as restricted distribution methods, patient registries, and 66 Table of Contents other risk minimization tools. Certain REMS programs can significantly impact and restrict the marketability of our products, even if our products are approved.
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. Certain REMS programs can significantly impact and restrict the marketability of our products, even if our products are approved.
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 103 Table of Contents further.
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 further.
Regardless of merit or eventual outcome, liability claims may result in: • decreased demand for any product candidates that we may develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial patients; • significant costs to defend the related litigation; • initiation of investigations by regulators; • diversion of our management’s time and resources; • substantial monetary awards to clinical trial patients; • product recalls, withdrawals, or labeling, marketing, or promotional restrictions; • exhaustion of any available insurance and our capital resources; • loss of revenue; 95 Table of Contents • the inability to commercialize any product candidates that we may develop; and • a decline in our stock price.
Regardless of merit or eventual outcome, liability claims may result in: • decreased demand for any product candidates that we may develop; • injury to our reputation and significant negative media attention; • withdrawal of clinical trial patients; • significant costs to defend any related product liability litigation; • initiation of investigations by regulators; • diversion of our management’s time and resources; 84 Tabl e of Contents • substantial monetary awards to clinical trial patients; • product recalls, withdrawals, or labeling, marketing, or promotional restrictions; • exhaustion of any available insurance and our capital resources; • loss of revenue; • the inability to commercialize any product candidates that we may develop; and • a decline in our stock price.
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.
We do not yet have sufficient information to reliably estimate the cost of manufacturing our product candidates for commercialization, and the actual cost to manufacture and process our product candidates could materially and adversely affect the commercial viability of our product candidates.
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. The same may happen with review of our product 64 Table of Contents candidates by foreign regulatory authorities.
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. The same may happen with review of our product candidates by foreign regulatory authorities.
Additionally, in November 2018, a researcher at the 68 Table of Contents 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.
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.
This may require new testing and regulatory interactions. In addition, a new CMO would have to be educated in, or develop substantially equivalent processes for, production of our product candidates; and 87 Table of Contents • as a result of pandemics or other public health crises, our CMOs and suppliers may experience production delays and shutdowns.
This may require new testing and regulatory interactions. In addition, a new CMO would have to be educated in, or develop substantially equivalent processes for, production of our product candidates; and • as a result of pandemics or other public health crises, our CMOs and suppliers may experience production delays and shutdowns.
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.
As of January 1, 2024, the MHRA is applying its new International Recognition Procedure (“IRP”) 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.
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. 100 Table of Contents 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.
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. 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.
Although an inadvertent lapse can, in many 76 Table of Contents 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.
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.
Even if we complete the necessary preclinical studies and clinical trials, the regulatory approval process is expensive, time-consuming, and uncertain, and we may be unable to obtain the regulatory approvals necessary for the commercialization of our product candidates; furthermore, if there are delays in obtaining regulatory approvals, we may not be able to commercialize our products, may lose competitive lead time, and our ability to generate revenues will be materially impaired .
Even if we complete the necessary preclinical studies and clinical trials, the regulatory approval process is expensive, time-consuming, and uncertain, and we may be unable to obtain the regulatory approvals necessary for the commercialization of our product candidates; furthermore, if there are delays in obtaining regulatory approvals, we 51 Tabl e of Contents may not be able to commercialize our products, may lose competitive lead time, and our ability to generate revenues will be materially impaired.
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 74 Table of Contents regulators if a breach of personal information occurs, which is a broader class of information than the health information protected by HIPAA.
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 regulators if a breach of personal information occurs, which is a broader class of information than the health information protected by HIPAA.
We expect our expenses to increase in connection with our ongoing activities, particularly as we initiate and continue clinical trials for, and seek marketing approval of, our product candidates.
We expect our expenses to increase in connection with our ongoing activities, particularly as we initiate additional clinical trials for, and seek marketing approval of, our product candidates.
However, we may not be 79 Table of Contents 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.
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.
Third-party payors, whether domestic or foreign, governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In both the United States and certain foreign jurisdictions, there have been a number of legislative and regulatory changes to healthcare systems that could impact our ability to sell our product candidates, if approved, profitably.
Third-party payors, whether domestic or foreign, governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In both the United States and certain foreign jurisdictions, there have 59 Tabl e of Contents been a number of legislative and regulatory changes to healthcare systems that could impact our ability to sell our product candidates, if approved, profitably.
However, for so long as we remain an emerging growth company as defined in the JOBS Act or a smaller reporting company, we intend to take advantage of certain exemptions from various reporting requirements that are applicable to public companies that are not emerging growth companies or smaller reporting companies, including, but not limited to, not being required to comply with the auditor attestation requirements of Section 404.
However, for so long as we remain an emerging growth company as defined in the JOBS Act or a smaller reporting company, we intend to take advantage of certain exemptions from various reporting requirements that are applicable to public companies that are not emerging growth companies or smaller reporting companies, including, but not limited to, not being required to comply with the auditor attestation requirements of 91 Tabl e of Contents Section 404.
Many of our competitors have substantially greater financial, technical, and other resources, such as larger research and development staffs, established manufacturing capabilities and facilities, and experienced marketing organizations with well-established sales forces. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies that have greater resources.
Many of our competitors have substantially greater financial, technical, and other resources, such as larger research and development staffs, established manufacturing capabilities and facilities, clinical trial expertise, and marketing organizations with well-established sales forces. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies that have greater resources.
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.
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 76 Tabl e of Contents the manufacture of recombinant viral vectors from an EU national regulatory authority.
The Alliance for Regenerative Medicine in Washington, D.C., of which we are a member, has called for a voluntary moratorium on the use of genome-editing technologies, including CRISPR, in research that involves altering human embryos or human germline cells and has also released a bioethical framework of principles for the use of genome editing in therapeutic applications endorsed by a number of companies that use genome-editing technologies.
The Alliance for Regenerative Medicine in Washington, D.C. has called for a voluntary moratorium on the use of genome-editing technologies, including CRISPR, in research that involves altering human embryos or human germline cells and has also released a bioethical framework of principles for the use of genome editing in therapeutic applications endorsed by a number of companies that use genome-editing technologies.
We may encounter delays in enrolling or be unable to enroll a 59 Table of Contents 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.
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 from our clinical trials before completion.
We may be subject to claims challenging the inventorship of our patents and other intellectual property. We may in the future be subject to claims that former employees, consultants, or other third parties have an interest in our patents or other intellectual property as an inventor, co-inventor, or owner of trade secrets.
We may in the future be subject to claims that former employees, consultants, or other third parties have an interest in our patents or other intellectual property as an inventor, co-inventor, or owner of trade secrets.
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. We 55 Table of Contents currently have no product revenue and we may never be able to successfully develop or commercialize a marketable product.
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. We currently have no product revenue and we may never be able to successfully develop or commercialize a marketable product.
There is uncertainty regarding the patentability of certain inventions in the biotechnology and pharmaceutical areas. Recent decisions by the U.S. Supreme Court have either narrowed the scope of patent protection available in certain circumstances or weakened the rights of patent owners in particular situations. For example, in Association for Molecular Pathology v.
There is uncertainty regarding the patentability of certain inventions in the biotechnology and pharmaceutical areas. Recent decisions by the U.S. Supreme Court have either narrowed the scope of patent protection available in certain 68 Tabl e of Contents circumstances or weakened the rights of patent owners in particular situations. For example, in Association for Molecular Pathology v.
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.
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 82 Tabl e of Contents monitoring and updating as technologies change and efforts to overcome security measures become increasingly sophisticated.
We may engage third parties to sell our product candidates outside the United States if we receive regulatory approval in such jurisdictions for our product candidates. We may also have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations.
We may engage third parties to sell our product candidates outside the United 62 Tabl e of Contents States if we receive regulatory approval in such jurisdictions for our product candidates. We may also have direct or indirect interactions with officials and employees of government agencies or government-affiliated hospitals, universities, and other organizations.
In the United States, each co-owner has the freedom to license and exploit the technology. As a result, although our license from UC/Vienna is exclusive, we do not have any rights from Dr. Charpentier and thus our license to the CVC IP from UC/ 83 Table of Contents Vienna is non-exclusive with respect to such co-owned rights.
In the United States, each co-owner has the freedom to license and exploit the technology. As a result, although our license from UC/Vienna is exclusive, we do not have any rights from Dr. Charpentier and thus our license to the CVC IP from UC/Vienna is non-exclusive with respect to such co-owned rights.
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.
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 service providers and vendors, and clinical sites, including personal information of our employees and, potentially, our clinical trial patients, and company and vendor confidential data.
Any product candidate for which we obtain marketing approval could be subject to restrictions or withdrawal from the market, and we may be subject to substantial penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, when and if any of them are approved.
Any product candidate for which we obtain marketing approval could be subject to restrictions or withdrawal from the market, and we may be subject to 54 Tabl e of Contents substantial penalties if we fail to comply with regulatory requirements or if we experience unanticipated problems with our products, when and if any of them are approved.
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 96 Table of Contents 382 and 383 of the Code.
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.
Because the 70 Table of Contents 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.
Because the 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.
Even if our product candidates are successful in clinical trials 71 Table of Contents 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.
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.
We can be held liable for the corrupt or other illegal activities of our employees, agents, contractors, and other collaborators, even if we do not explicitly authorize or have actual knowledge of these activities.
We can be held liable for the corrupt or other illegal activities of our employees, consultants, and other collaborators, even if we do not explicitly authorize or have actual knowledge of these activities.
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.
As a result, they may be unavailable to offset future taxes. 85 Tabl e of Contents 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.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeWe describe whether and how risks from identified cybersecurity threats, including as a result of any previous cybersecurity incidents, have materially affected or are reasonably likely to materially affect us, including our business strategy, results of operations, or financial condition, see Risk Factors - “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,” in Item 1A of this Annual Report on Form 10-K.
Biggest changeFor additional information regarding risks we face, see Risk Factors - “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, ” in Item 1A of this Annual Report on Form 10-K.
These individuals are informed about and monitor the prevention, mitigation, detection, and remediation of cybersecurity incidents through their management of, and participation in, our cybersecurity risk management and strategy processes, and report to the audit committee on any appropriate items. 105 Table of Contents
These individuals are informed about and monitor the prevention, mitigation, detection, and remediation of cybersecurity incidents through their management of, and participation in, our cybersecurity risk management and strategy processes, and report to the audit committee on any appropriate items. 94 Tabl e of Contents
Added
We do not believe that there are currently any risks from known cybersecurity threats that have materially affected or are reasonably likely to materially affect us, including our business strategy, results of operations, or financial condition.

Item 2. Properties

Properties — owned and leased real estate

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Biggest changeItem 2. Properties. Our corporate headquarters are located in Berkeley, California, where we lease approximately 61,735 and 10,000 square feet of research and development, laboratory, and office space. These leases expire in March 2031 and July 2032, respectively. We have the ability to extend these leases for an additional five years each.
Biggest changeItem 2. Properties. Our corporate headquarters are located in Berkeley, California, where we lease approximately 71,735 square feet of laboratory and office space under two leases. These leases expire in March 2031, and July 2032. We have the ability to extend these leases for an additional five years each.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeRegardless of the outcome, litigation can have a material adverse effect on us due to defense and settlement costs, diversion of management resources, and other factors. On April 11, 2023, a putative class action lawsuit was filed in the U.S.
Biggest changeItem 3. Legal Proceedings. From time to time, we may become involved in litigation arising in the ordinary course of business. Regardless of the outcome, litigation can have a material adverse effect on us due to defense and settlement costs, diversion of our management resources, and other factors.
The Bergman complaint challenges disclosures regarding our company’s business, operations, and prospects, specifically with respect to the alleged durability of CB-010’s therapeutic effect and the product candidate’s clinical and commercial prospects, in alleged violation of Sections 11 and 15 of the Securities Act and Sections 10(b) and 20(a) of the Exchange Act.
The Bergman Case complaint challenged disclosures regarding our company’s business, operations, and prospects, specifically with respect to the alleged durability of CB-010’s therapeutic effect and the product candidate’s clinical and commercial prospects, in alleged violation of Sections 11 and 15 of the Securities Act and Sections 10(b) and 20(a) of the Exchange Act.
On September 18, 2023, plaintiffs filed an amended complaint adding the IPO underwriters as defendants and making substantially the same allegations as the original complaint. On November 14, 2023, we filed a motion to dismiss the amended complaint for failure to state a claim.
On September 18, 2023, plaintiffs filed an amended complaint adding the IPO underwriters as defendants and making substantially the same allegations as the original complaint. On November 14, 2023, we filed a motion to dismiss the amended complaint for failure to state a claim. Motion to dismiss briefing was completed on February 21, 2024.
On March 22, 2023, a putative class action lawsuit was filed in Superior Court of the State of California for the County of Alameda against our company and certain of our officers and current and former members of our board of directors, Lowry v. Caribou Biosciences, Inc., et al. , Case Number T23-1084 (“Lowry Case”).
On April 11, 2023, a putative class action lawsuit was filed in the U.S. District Court for the Northern District of California against our company and certain of our officers and current and former members of our board of directors, Bergman v. Caribou Biosciences, Inc., et al., case number 3:23-cv-01742 (“Bergman Case”).
The Lowry Case challenges disclosures regarding our company’s business, operations, and prospects, specifically with respect to the alleged durability of CB-010’s therapeutic effect and the product candidate’s clinical and commercial prospects, in alleged violation of Sections 11 and 15 of the Securities Act.
The Saylor Case complaint challenges disclosures regarding our business, operations, and prospects, specifically with respect to the alleged safety, efficacy, and durability of CB-010, CB-010’s clinical results and commercial prospects, and our financial statements, in alleged violation of Sections 10(b) and 20(a) of the Exchange Act. The lawsuit is at the preliminary stage of the proceedings.
District Court for the Northern District of California against our company and certain of our officers and current and former members of our board of directors, B ergman v. Caribou Biosciences, Inc., et al. , Case Number 4:23-cv-01742-YGR (“Bergman Case”).
On March 3, 2025, a shareholder derivative complaint was filed in the U.S. District Court for the Northern District of California against our directors and certain of our current and former officers, Moisio, derivatively on behalf of Caribou Biosciences, Inc. v.
Removed
Item 3. Legal Proceedings. From time to time, we may be subject to various legal proceedings and claims that arise in the ordinary course of our business activities. The outcome of any such proceedings or claims, irrespective of the merits, is inherently uncertain.
Added
On April 22, 2024, we reached an agreement in principle with plaintiffs to settle the Bergman Case for $3.9 million in exchange for a full release of the putative class’s claims against us and all our current and former officers, current and former members of our board of directors, the IPO underwriters, and the other named defendant.
Removed
Motion to dismiss briefing was completed on February 21, 2024, and oral argument on the motion is scheduled for April 23, 2024. We intend to vigorously defend the claims asserted against us.
Added
On February 18, 2025, the court issued an order granting final approval of the settlement. On December 24, 2024, a putative class action lawsuit was filed in the U.S. District Court for the Northern District of California against our company and certain of our current and former officers, Saylor v.
Removed
The allegations and claims in the Lowry Case are substantially similar to the Securities Act claims asserted in the Bergman Case. On April 26, 2023, we filed a motion to stay the Lowry Case during the pendency of the parallel federal court litigation in the Bergman Case, and, on July 11, 2023, our motion to stay was denied.
Added
Caribou Biosciences, Inc., et al., c ase number 3:24-cv-09413 (“Saylor Case”). The alleged class period is July 14, 2023, to July 16, 2024.
Removed
On September 11, 2023, plaintiff filed an amended complaint making substantially the same allegations as the original complaint. On November 9, 2023, we filed a motion to dismiss the amended complaint on the grounds that our certification of incorporation mandates that Securities Act claims against us be brought in federal court.
Added
Haurwitz, et al, case number 4:25-cv-02199 (“Derivative Case”), alleging, among other things, that the named directors and officers breached their fiduciary duties by causing our company to make the disclosures being challenged in the Saylor Case and seeking unspecified monetary damages for our company as well as that we make certain changes to our corporate governance.
Removed
On February 28, 2024, the court granted our motion to dismiss and ordered the case dismissed. Item 4. Mine Safety Disclosures. Not applicable. 106 Table of Contents PART II
Added
The Derivative Case is at the preliminary stage of the proceedings. Item 4. Mine Safety Disclosures. Not applicable.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeRecent Sales of Unregistered Securities We had no sales of unregistered equity securities during the period covered by this Annual Report that were not previously reported in a Current Report on Form 8-K (or on Form 10-Q in lieu of Form 8-K). Purchases of Equity Securities by the Issuer and Affiliated Purchasers None. Item 6. [Reserved] 107 Table of Contents
Biggest changeRecent Sales of Unregistered Securities We had no sales of unregistered equity securities during the period covered by this Annual Report that were not previously reported in a Current Report on Form 8-K (or on Form 10-Q in lieu of Form 8-K). Purchases of Equity Securities by the Issuer and Affiliated Purchasers None.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our common stock is traded on the Nasdaq Global Select Market under the symbol “CRBU.” Holders As of March 5, 2024, we had 40 holders of record of our common stock.
Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities. Market Information Our common stock is traded on the Nasdaq Global Select Market under the symbol “CRBU.” Holders As of March 4, 2025, we had 35 holders of record of our common stock.
Removed
Use of Proceeds from our IPO On July 22, 2021, our Registration Statement on Form S-1 (File No. 333-257604) relating to our initial public offering (“IPO”) of our common stock was declared effective by the U.S. Securities and Exchange Commission (“SEC”).
Removed
On July 22, 2021, we filed a second Registration Statement on Form S-1 (File No. 333-258105) pursuant to Rule 462(b) of the Securities Act of 1933, as amended (“Securities Act”), which was effective immediately upon filing.
Removed
Our net proceeds from our IPO, after deducting underwriting discounts and commissions and estimated offering expenses of $28.6 million, were $321.0 million, including the proceeds from shares issued upon the exercise in full of the underwriters’ overallotment option.
Removed
There has been no material change in our planned use of the net proceeds from our IPO from that described in the final prospectus for our IPO filed with the SEC pursuant to Rule 424(b)(4) under the Securities Act on July 23, 2021.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThe duration, costs, and timing of preclinical studies, clinical trials, and development of our product candidates will depend on a variety of factors, including: • sufficiency of our financial and other resources; • acceptance of our CRISPR chRDNA genome-editing technology; • ability to develop differentiating features so that our products have a competitive edge; • completion of preclinical studies; • establishment, maintenance, enforcement, and defense of our patents and other intellectual property rights; • our ability to not infringe, misappropriate, or otherwise violate third-party intellectual property rights; • clearance of IND applications to initiate clinical trials on new product candidates; • successful enrollment in, and completion of, our clinical trials on our product candidates; • data from our clinical trials that support an acceptable risk-benefit profile of our product candidates for the intended patient populations and that demonstrate safety and efficacy; • entry into collaborations to further the development of our product candidates or for the development of new product candidates; • successful development of our internal process development and transfer to larger-scale facilities; • establishment of agreements with CMOs and suppliers for clinical and commercial supplies and scaling up manufacturing processes and capabilities to support our clinical trials; • receipt of marketing approvals from applicable regulatory authorities; 111 Table of Contents • grant of regulatory exclusivity for our product candidates; • establishment of sales, marketing, and distribution capabilities necessary for commercialization of our product candidates if and when approved, whether by us or in collaboration with third parties; • maintenance of a continued acceptable safety profile of our products post-approval; • acceptance of our product candidates, if and when approved by the applicable regulatory authorities, by patients, the medical community, and third-party payors; • ability of our products to compete with other therapies and treatment options; • establishment and maintenance of healthcare coverage and adequate reimbursement; and • expanded indications and patient populations for our products.
Biggest changeThe duration, costs, and timing of preclinical studies, clinical trials, and development of our product candidates will depend on a variety of factors, including: • sufficiency of our financial and other resources; • acceptance of our CRISPR chRDNA genome-editing technology; • ability to develop differentiating features so that our products have a competitive edge; • completion of preclinical studies; • establishment, maintenance, enforcement, and defense of our patents and other intellectual property rights; • our ability to not infringe, misappropriate, or otherwise violate third-party intellectual property rights; • timely clearance of IND applications to initiate clinical trials of new product candidates; • successful enrollment in, and completion of, our clinical trials of our product candidates; • data from our clinical trials that support an acceptable risk-benefit profile of our product candidates for the intended patient populations and that demonstrate safety and efficacy; • entry into collaborations to further the development of our product candidates or for the development of new product candidates; • successful development of our internal process development and transfer to larger-scale facilities; • establishment of agreements with CMOs and suppliers for clinical and commercial supplies and scaling up manufacturing processes and capabilities to support our clinical trials; • receipt of timely responses and marketing approvals from applicable regulatory authorities; • grant of regulatory exclusivity for our product candidates; • establishment of sales, marketing, and distribution capabilities necessary for commercialization of our product candidates if and when approved, whether by us or in collaboration with third parties; • maintenance of a continued acceptable safety profile of our products post-approval; • acceptance of our product candidates, if and when approved by the applicable regulatory authorities, by patients, the medical community, and third-party payors; • ability of our products to compete with other therapies and treatment options; • establishment and maintenance of healthcare coverage and adequate reimbursement; and • expanded indications and patient populations for our products. 102 Tabl e of Contents The following table summarizes our research and development expenses for the periods indicated: Year Ended December 31, 2024 2023 Change (in thousands) External costs: Expenses related to licenses, sublicensing revenue, and milestones $ 4,828 $ 2,777 $ 2,051 Services provided by CROs, CMOs, and third parties that conduct preclinical studies and clinical trials on our behalf 49,261 45,777 3,484 Other research and development expenses 23,560 16,967 6,593 Total external costs 77,649 65,521 12,128 Internal costs: Personnel-related expenses 39,531 35,411 4,120 Facilities and other allocated expenses 12,973 11,143 1,830 Total internal costs 52,504 46,554 5,950 Total research and development expenses $ 130,153 $ 112,075 $ 18,078 General and Administrative Expenses Our general and administrative expenses consist primarily of personnel-related costs, intellectual property costs, consulting costs, and allocated overhead, including rent, equipment depreciation, and utilities.
For the foreseeable future, we expect substantially all of our revenue will be generated from licensing and collaboration agreements. Operating Expenses Research and Development Expenses Our research and development expenses consist of internal and external expenses incurred in connection with the development of our product candidates and our platform technologies, and our in-licensing, assignment, and other third-party agreements.
For the foreseeable future, we expect substantially all our revenue will be generated from licensing and collaboration agreements. Operating Expenses Research and Development Expenses Our research and development expenses consist of internal and external expenses incurred in connection with the development of our product candidates and our platform technologies, and our in-licensing, assignment, and other third-party agreements.
In July and August 2023, we issued and sold a total of 22,115,384 shares of our common stock in an underwritten follow-on public offering at a price to the public of $6.50 per share, which included the full exercise of the underwriters’ right to purchase 2,884,615 additional shares of our common stock.
Follow-on Public Offering In July and August 2023, we issued and sold a total of 22,115,384 shares of our common stock in an underwritten follow-on public offering at a price of $6.50 per share, which included the full exercise of the underwriters’ right to purchase 2,884,615 additional shares of our common stock.
Unless otherwise agreed by Pfizer, we have agreed to use the proceeds from the Pfizer Investment solely in connection with (i) the development program for our allogeneic anti-BCMA CAR-T cell therapy known as CB-011 product candidate that is being evaluated in our CaMMouflage clinical trial and/or (ii) any other single-targeted anti-BCMA CAR-T cell therapy using an anti-BCMA single-chain variable fragment owned or controlled by us (collectively, cell therapies described in clauses (i) and (ii) are referred to as a “BCMA Product Candidate”), for 36 months beginning on June 29, 2023.
Unless otherwise agreed by Pfizer, we have agreed to use the proceeds from the Pfizer Investment solely in connection with (i) the development program for our allogeneic anti-BCMA CAR-T cell therapy product candidate (CB-011) that is being evaluated in our CaMMouflage phase 1 clinical trial and/or (ii) any other single-targeted anti-BCMA CAR-T cell therapy using an anti-BCMA single-chain variable fragment owned or controlled by us (collectively, cell therapies described in clauses (i) and (ii) are referred to as a “BCMA Product Candidate”), for 36 months beginning on June 29, 2023.
We will pay Jefferies a commission equal to 3.0% of the aggregate gross proceeds of any shares sold through Jefferies pursuant to the ATM Sales Agreement.
We pay Jefferies a commission equal to 3.0% of the aggregate gross proceeds of any shares sold through Jefferies pursuant to the ATM Sales Agreement.
The changes in our net operating assets and liabilities were due to decreases of $16.9 million in deferred revenue and $0.6 million in operating lease liabilities, partially offset by increases of $5.7 million in accrued expenses and other current liabilities, $1.8 million in accounts payable, and decreases of $1.8 million in prepaid expenses and other current assets and $0.8 million in contract assets.
The changes in our net operating assets and liabilities were due to decreases of $16.9 million in deferred revenue and $0.6 million in operating lease liabilities, partially offset (i) by increases of $5.7 million in accrued expenses and other current liabilities, $1.8 million in accounts payable, and (ii) decreases of $1.8 million in prepaid expenses and other current assets and $0.8 million in contract assets.
Funding Requirements Our primary use of cash is to fund operating expenses and research and development expenditures. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable, accrued expenses, and prepaid expenses.
Our primary use of cash is to fund operating expenses and research and development expenditures. Cash used to fund operating expenses is impacted by the timing of when we pay these expenses, as reflected in the change in our outstanding accounts payable, accrued expenses, and prepaid expenses.
This discussion and analysis contain forward-looking statements, including statements regarding our intentions, plans, objections and expectations for our business. Forward-looking statements are based upon current beliefs, plans and expectations related to future events and our future financial performance and are subject to risks, uncertainties and assumptions.
This discussion and analysis contain forward-looking statements, including statements regarding our intentions, plans, projections and expectations for our business. Forward-looking statements are based upon current beliefs, plans and expectations related to future events and our future financial performance and are subject to risks, uncertainties and assumptions.
We expect that our research and development expenses will increase substantially for the foreseeable future as we continue to implement our business strategy; advance our product candidates through clinical trials and later stages of development; conduct preclinical studies and clinical trials for our other product candidates; seek regulatory approvals for any product candidates that successfully complete clinical trials; expand our research and development efforts and incur expenses associated with hiring additional personnel to support our research and development efforts; and seek to identify, in-license, acquire, and/or develop additional product candidates.
We expect that our research and development expenses will increase substantially for the foreseeable future as we continue to implement our business strategy; advance our product candidates through clinical trials and commercialization; conduct preclinical studies and clinical trials for our other product candidates; seek regulatory approvals for any product candidates that successfully complete clinical trials; expand our research and development efforts and incur expenses associated with hiring additional personnel to support our research and development efforts; and seek to identify, in-license, acquire, and/or develop additional product candidates.
We expect to continue to rely on our CMOs for the manufacturing of our preclinical study and clinical trial materials, and most of these 109 Table of Contents CMOs have capabilities for commercial manufacturing. Additionally, we may decide to build our own manufacturing facility in the future to provide greater flexibility and control over our clinical or commercial manufacturing needs.
We expect to continue to rely on our CMOs for manufacturing our preclinical study and clinical trial materials, and most of these CMOs have capabilities for commercial manufacturing. Additionally, we may decide to build our own manufacturing facility in the future to provide greater flexibility and control over our clinical or commercial manufacturing needs.
Until we can generate significant revenue from product sales, if ever, we expect to finance our operations through equity offerings (including our at-the-market facility), debt financings, collaborations and strategic alliances, licensing arrangements, or other sources.
Until we can generate significant revenue from product sales, if ever, we expect to finance our operations through equity offerings (including our at-the-market equity offering program), debt financings, collaborations and strategic alliances, licensing arrangements, and/or other sources.
Such license agreements require payments of non-refundable annual license fees by the licensees (referred to as maintenance fees in the license agreements), which are accounted for as material rights for license renewals. 119 Table of Contents We recognize revenue when the license is delivered and the term commences.
Such license agreements require payments of non-refundable annual license fees by the licensees (referred to as maintenance fees in the license agreements), which are accounted for as material rights for license renewals. We recognize revenue when the license is delivered and the term commences.
We have elected to use this extended transition period for complying with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date that we (a) are no longer an emerging growth company or (b) affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act.
We have elected to use this extended transition period for complying with new or revised accounting standards that have different effective dates for public and private companies until the earlier of the date that we (i) are no longer an emerging growth company or (ii) affirmatively and irrevocably opt out of the extended transition period provided in the JOBS Act.
Our 2023 non-cash charges were primarily comprised of $13.8 million of stock-based compensation, $3.5 million of depreciation and amortization expense, $2.0 million of non-cash lease expense, and change in the fair value of the MSKCC success payments liability of $1.3 million, which were partially offset by the accretion of discounts on marketable securities of $4.4 million.
Our 2023 non-cash charges were primarily comprised of (i) $13.8 million of stock-based compensation, (ii) $3.5 million of depreciation and amortization expense, (iii) $2.0 million of non-cash lease expense, and (iv) change in the fair value of the MSKCC success payments liability of $1.3 million, which were partially offset by accretion of discounts on marketable securities of $4.4 million.
Specifically, as a smaller reporting company, we may choose to present only the two most recent fiscal years of audited consolidated financial statements in our Annual Report on Form 10-K and, similar to emerging growth companies, smaller reporting companies have reduced disclosure obligations regarding executive compensation.
Specifically, as a smaller reporting company, we may choose to present only the two most recent fiscal years of audited consolidated financial statements in our Annual Report on Form 10-K and, similar to 111 Tabl e of Contents emerging growth companies, smaller reporting companies have reduced disclosure obligations regarding executive compensation.
On August 9, 2022, we entered into an Open Market Sale Agreement SM (the “ATM Sales Agreement”) with Jefferies LLC (“Jefferies”), pursuant to which, upon the terms and subject to the conditions and limitations set forth in the ATM Sales Agreement, we may, from time to time, in our sole discretion, issue and sell, through Jefferies, acting as sales agent, up to $100.0 million of our shares of common stock, by any method permitted by law deemed to be an “at the 114 Table of Contents market offering” as defined in Rule 415(a)(4) of the Securities Act of 1933, as amended (“Securities Act”).
At-the-Market Equity Offering Program On August 9, 2022, we entered into an Open Market Sale Agreement SM (the “ATM Sales Agreement”) with Jefferies LLC (“Jefferies”), pursuant to which, upon the terms and subject to the conditions and limitations set forth in the ATM Sales Agreement, we may, from time to time, in our sole discretion, issue and sell, through Jefferies, acting as sales agent, up to $100.0 million of our shares of common stock, by any method permitted by law deemed to be an “at the market offering” as defined in Rule 415(a)(4) of the Securities Act of 1933, as amended (“Securities Act”).
This increase primarily relates to a $16.8 million increase in revenue recognized under the now-terminated Collaboration and License Agreement (as amended, “AbbVie Agreement”) with AbbVie Manufacturing Management Unlimited Company (“AbbVie”). In connection with the termination of the AbbVie Agreement, we recognized the remaining deferred revenue of $20.8 million during the year ended December 31, 2023.
This decrease primarily relates to a $24.8 million decrease in revenue recognized under the now-terminated Collaboration and License Agreement (as amended, “AbbVie Agreement”) with AbbVie Manufacturing Management Unlimited Company (“AbbVie”). In connection with the termination of the AbbVie Agreement, we recognized the remaining deferred revenue of $20.8 million during the year ended December 31, 2023.
We are also unable to predict when, if ever, we will generate revenue and material net cash inflows from the commercialization and sale of any of our product candidates for which we may obtain marketing approval. We may never succeed in achieving regulatory approval for any of our product candidates.
We are also unable to predict when, if ever, we will generate revenue and material net cash inflows from the commercialization and sale of any of our product candidates for which we may obtain marketing approval. We may never succeed in achieving regulatory 101 Tabl e of Contents approval for any of our product candidates.
To date, we have primarily funded our operations through proceeds from the sales of our capital stock, revenue from our license and collaboration agreements, and proceeds from the sale of shares of Intellia Therapeutics, Inc. (“Intellia”) common stock. Our net losses for the years ended December 31, 2023 and 2022 were $102.1 million and $99.4 million, respectively.
To date, we have primarily funded our operations through proceeds from the sales of our capital stock, revenue from our license and collaboration agreements, and proceeds from the sale of shares of Intellia Therapeutics, Inc. (“Intellia”) common stock. Our net losses for the years ended December 31, 2024, and 2023 were $149.1 million and $102.1 million, respectively.
We are also a “smaller reporting company.” If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available 121 Table of Contents to smaller reporting companies.
We are also a “smaller reporting company.” If we are a smaller reporting company at the time we cease to be an emerging growth company, we may continue to rely on exemptions from certain disclosure requirements that are available to smaller reporting companies.
As of December 31, 2023 the timing and likelihood of triggering the MSKCC success payments are uncertain. See note 4 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for more information about the MSKCC success payments liability. Leases We have operating lease agreements for our office spaces.
As of December 31, 2024, the timing and likelihood of triggering the MSKCC success payments are uncertain. See Note 4 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for more information about the MSKCC success payments liability. Leases We have two operating lease agreements for our laboratory and office space.
Our accrual is dependent, in part, upon the receipt of timely and accurate reporting from CROs, CMOs, and other third-party vendors.
Our accrual is dependent, in part, upon the receipt of timely and accurate reporting from CROs, CMOs, and other third-party service providers.
Our future funding requirements will depend on many factors, including the following: • the initiation, progress, timing, costs, and results of preclinical studies and clinical trials for our product candidates; • the clinical development plans we establish for these product candidates; • the number and characteristics of the product candidates that we develop; • increases in the number of our employees and expansion of our physical facilities to support growth initiatives; • the outcome, timing, and cost of meeting regulatory requirements established by the FDA and other comparable foreign regulatory authorities; 116 Table of Contents • whether we enter into any collaboration agreements and the terms of any such agreements; • the cost of filing and prosecuting our patent applications, and maintaining and enforcing our patents and other intellectual property rights; • the extent to which we acquire or in-license other product candidates and technologies; • the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against our products after we receive regulatory approval; • the effect of competing technological and market developments; • the cost and timing of completion of commercial-scale outsourced manufacturing activities or the cost and timing of completion of clinical-scale and commercial-scale internal manufacturing activities; • the cost of establishing sales, marketing, and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products without a partner; • the amount of revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive marketing approval; • the achievement of milestones or occurrence of other developments that trigger payments by or to third parties; • our implementation of various computerized informational systems and efforts to enhance operational systems; • the impact of public health crises or geopolitical events on our clinical development or operations; • the impact of inflationary pressures on the cost of our operations; and • the costs associated with being a public company.
Our future funding requirements will depend on many factors, including the following: • the initiation, progress, timing, costs, and results of preclinical studies for our programs and clinical trials for our product candidates; • the clinical development plans we establish for these product candidates; • the number and characteristics of the product candidates that we develop; • increases in the number of our employees and expansion of our physical facilities to support growth initiatives; • the outcome, timing, and cost of meeting regulatory requirements established by the FDA and other comparable foreign regulatory authorities; • the potential impact of proposed reductions in government spending and personnel under the new Administration; • whether we enter into any collaboration agreements and the terms of any such agreements; • the cost of filing and prosecuting our patent applications, and maintaining and enforcing our patents and other intellectual property rights; • the extent to which we acquire or in-license other product candidates, intellectual property, and new technologies; • the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against our products after we receive regulatory approval; • the effect of competing technological and market developments; 106 Tabl e of Contents • the cost and timing of completion of commercial-scale outsourced manufacturing activities or the cost and timing of completion of clinical-scale and commercial-scale internal manufacturing activities; • the cost of establishing sales, marketing, and distribution capabilities for any product candidates for which we may receive regulatory approval in regions where we choose to commercialize our products without a partner; • the amount of revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive marketing approval; • the achievement of milestones or occurrence of other developments that trigger payments by or to third parties; • our implementation of various computerized informational systems and efforts to enhance operational systems; • the impact of public health crises or geopolitical events on our clinical development or operations; • the impact of inflationary pressures on the cost of our operations; and • the costs of operating as a public company, including defending against class action securities litigation.
We use our chRDNA technologies to armor our cell therapies through multiple genome-editing strategies, such as checkpoint disruption, immune cloaking, or a combination of these two strategies, to enhance activity against devastating diseases.
We use our chRDNA technologies to armor our cell therapies through multiple genome-editing strategies, such as checkpoint disruption, immune cloaking, or a combination of these two strategies, to enhance allogeneic CAR-T cell therapy activity against diseases.
We had an accumulated deficit of $299.3 million as of December 31, 2023. Our net losses and operating losses may fluctuate from quarter to quarter and year to year depending primarily on the timing of expenses associated with our clinical trials and nonclinical studies and our other research and development expenses.
We had an accumulated deficit of $448.4 million as of December 31, 2024. Our net losses and operating losses may fluctuate from quarter to quarter and year to year depending primarily on the timing of expenses associated with our clinical trials and nonclinical studies and our other research and development expenses.
We use multiple contract manufacturing organizations (“CMOs”) to individually manufacture, under current good manufacturing processes, our chRDNA guides, Cas9 and Cas12a proteins, plasmids, and adeno-associated virus serotype 6 (“AAV6”) vectors used in the manufacture of our cell therapy product candidates as well as the CAR-T and CAR-NK cell therapy product candidates themselves.
We do not own or operate any manufacturing facilities. We use multiple contract manufacturing organizations (“CMOs”) to individually manufacture, under current good manufacturing processes, our chRDNA guides, Cas9 and Cas12a proteins, plasmids, and adeno-associated virus serotype 6 (“AAV6”) vectors used in the manufacture of our cell therapy product candidates as well as the CAR-T cell therapy product candidates themselves.
During the years ended December 31, 2023 and 2022, we recorded $1.5 million and $3.5 million, respectively, of patent cost reimbursements as a reduction to general and administrative expense.
During the years ended December 31, 2024, and 2023, we recorded $1.2 million and $1.5 million, respectively, of patent cost reimbursements as a reduction to general and administrative expenses.
Revenue under such licensing and collaboration agreements was $34.5 million and $13.9 million for the years ended December 31, 2023 and 2022, respectively. See Note 4 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information.
Each of these payments results in licensing and collaboration revenue. Revenue under such licensing and collaboration agreements was $10.0 million and $34.5 million for the years ended December 31, 2024, and 2023, respectively. See Note 4 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information.
The relevant time period commences when the first patient is dosed with our first CLL-1 product candidate (CB-012) in the first phase 1 clinical trial and ends upon the earlier of the third anniversary of approval of our biologics license application (“BLA”) by the FDA or 10 years from the date the first patient was dosed with our first CLL-1 product candidate in the first phase 1 clinical trial.
The relevant time period commenced on February 13, 2024, when the first patient was dosed with our anti-CLL-1 product candidate (CB-012) in our AMpLify phase 1 clinical trial and ends upon the earlier of the third anniversary of approval of our biologics license application (“BLA”) by the FDA or 10 years from February 13, 2024.
As of December 31, 2023, we had lease payment obligations totaling $41.7 million, of which $3.5 million is due within 12 months. 115 Table of Contents Strategic Investment On June 29, 2023, we entered into a Securities Purchase Agreement (“Securities Purchase Agreement”) with Pfizer, Inc.
As of December 31, 2024, we had lease payment obligations totaling $38.1 million, of which $4.3 million is due within 12 months. Strategic Investment On June 29, 2023, we entered into a Securities Purchase Agreement (“Securities Purchase Agreement”) with Pfizer, Inc.
The terms of these arrangements typically include payments to us of one or more of the following: nonrefundable, upfront license fees or exclusivity fees; annual maintenance fees; regulatory and/or commercial milestone payments; research and development payments; and royalties on the net sales of products and/or services. Each of these payments results in licensing and collaboration revenue.
The terms of these arrangements typically include payments to us of one or 100 Tabl e of Contents more of the following: nonrefundable, upfront license fees or exclusivity fees; annual maintenance fees; regulatory and/or commercial milestone payments; research and development payments; and royalties on the net sales of products and/or services.
The changes in our net operating assets and liabilities were due to decreases of $4.8 million in deferred revenue, $2.7 million in accounts payable, $0.4 million in operating lease liabilities, and increases of $1.0 million in prepaid expenses and other current assets, $0.8 million in contract assets, and $0.6 million in other assets, partially offset by increases of $2.0 million in accrued expenses and other current liabilities, and decreases of $3.3 million in other receivables, and $1.0 million in accounts receivable.
The changes in our net operating assets and liabilities were primarily due to (i) increases of $3.9 million in other assets and $0.4 million in prepaid expenses and other current assets, and (ii) decreases of $2.5 million in deferred revenue, current and long-term, $0.6 million in operating lease liabilities, and $0.4 million in accounts payable; partially offset by (i) decreases of $0.5 million in other receivables and $0.3 million in contract assets, and (ii) an increase of $2.1 million in accrued expenses and other current liabilities.
However, payments made prior to the receipt of goods or services that will be used or rendered for future research and development activities are deferred and capitalized as prepaid expenses and other current assets on our consolidated balance sheets. The capitalized amounts are recognized as expenses as the goods are delivered or as related services are performed.
Costs of certain activities are recognized based on an evaluation of the progress to completion of specific tasks. However, payments made prior to the receipt of goods or services that will be used or rendered for future research and development activities are deferred and capitalized as prepaid expenses and other current assets on our consolidated balance sheets.
Our therapies are directed at established cell surface targets for which autologous CAR-T cell therapeutics have already demonstrated clinical proof of concept, including CD19 and B cell maturation antigen (“BCMA”), as well as targets such as C-type lectin-like molecule-1 (“CLL-1,” also known as CD371).
Our allogeneic CAR-T cell therapy product candidates in clinical development are directed at established cell surface targets against which autologous CAR-T cell therapeutics have already demonstrated clinical proof of concept, including CD19 and B cell maturation antigen (“BCMA”), as well as targets such as C-type lectin-like molecule-1 (“CLL-1”).
Our 2022 non-cash charges were primarily comprised of $11.7 million of stock-based compensation, $2.0 million of non-cash lease expense, $1.6 million of depreciation and amortization expense, and $0.6 million of acquired in-process research and development, which were partially offset by the change in the fair value of the MSKCC success payments liability of $2.4 million, and accretion of discounts on marketable securities of $0.8 million.
Our 2024 non-cash charges were primarily comprised of (i) $16.7 million of stock-based compensation, (ii) $3.9 million of depreciation and amortization expense, (iii) $2.2 million of non-cash lease expense, and (iv) $1.6 million of acquired in-process research and development; which were partially offset by (i) accretion of discounts on marketable securities of $4.7 million, (ii) change in the fair value of the MSKCC success payments liability of $2.2 million, and (iii) non-cash consideration for licensing and collaboration revenue of $1.6 million.
Cash Provided by Financing Activities During the years ended December 31, 2023 and 2022, cash provided by financing activities was $154.3 million and $2.1 million, respectively. 118 Table of Contents Cash provided by financing activities for the year ended December 31, 2023 was due to proceeds from a follow-on public offering, net of offering expenses, of $134.4 million, proceeds from issuance of common stock in a private placement with Pfizer of $17.3 million, the exercise of stock options and purchases of common stock under the 2021 Employee Stock Purchase Plan (“ESPP”) of $1.6 million, and proceeds from issuance of common stock related to an at-the-market offering, net of offering expenses, of $1.0 million.
Cash provided by financing activities for the year ended December 31, 2023, was due to proceeds from a follow-on public offering, net of offering expenses, of $134.4 million, proceeds from issuance of common stock in a private placement with Pfizer of $17.3 million, the exercise of stock options and purchases of common stock under the ESPP of $1.6 million, and proceeds from issuance of common stock related to our at-the-market equity offering program, net of offering expenses, of $1.0 million.
For the year ended December 31, 2023, we sold 168,635 shares of our common stock under the ATM Sales Agreement at an average price per share of $7.32 for aggregate gross proceeds of $1.2 million ($1.0 million net of offering expenses).
During the year ended December 31, 2024, we sold 3,420,061 shares of our common stock, in a series of sales, at an average price of $4.58 per share under the ATM Sales Agreement for aggregate gross proceeds of $15.7 million ($15.2 million net of offering expenses). 105 Tabl e of Contents During the year ended December 31, 2023, we sold 168,635 shares of our common stock, in a series of sales, at an average price of $7.32 per share under the ATM Sales Agreement for aggregate gross proceeds of $1.2 million ($1.0 million net of offering expenses).
We anticipate that our expenses will increase substantially as we: • advance the ANTLER phase 1 clinical trial and initiate the planned pivotal phase 3 clinical trial for our CB-010 product candidate, the CaMMouflage phase 1 clinical trial for our CB-011 product candidate, and the AMpLify phase 1 clinical trial for our CB-012 product candidate; • 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, technical operations, and scientific personnel; • seek to identify additional research programs and additional product candidates; • further develop our genome-editing technologies; • acquire or in-license technologies; • expand, maintain, enforce, and defend our intellectual property portfolio; • seek regulatory and marketing approvals for any of our product candidates that successfully complete clinical trials, if any; • establish and expand manufacturing capabilities and supply chain capacity for our product candidates; • add operational, legal, financial, and management information systems and personnel; • experience any delays, challenges, or other issues associated with any of the above, including the failure of clinical trials meeting endpoints, unanticipated preclinical 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, agreements with third parties; • establish a sales, marketing, and distribution infrastructure to commercialize any product candidates for which we obtain marketing approval; and • continue to operate as a public company.
We anticipate that our expenses will increase substantially as we: • advance clinical trials for our CAR-T cell therapy product candidates; 99 Tabl e of Contents • 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 personnel, as needed; • seek to identify additional research programs and additional product candidates; • further develop our genome-editing technologies; • acquire or in-license intellectual property or new technologies; • expand, maintain, enforce, and defend our intellectual property portfolio; • seek regulatory and marketing approvals for any of our product candidates that successfully complete clinical trials, if any; • expand manufacturing capabilities and supply chain capacity for our product candidates; • experience any delays, challenges, or other issues associated with any of the above, including the failure of clinical trials meeting endpoints, unanticipated preclinical 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, agreements with third parties; • establish a sales, marketing, and distribution infrastructure to commercialize any product candidates for which we obtain marketing approval; and • continue to operate as a public company, including defending against any class action securities litigation.
Cash used in investing activities for the year ended December 31, 2022 was primarily due to our purchases of marketable securities of $339.1 million, purchases of property and equipment of $6.5 million, and in-process research and development of $0.6 million, partially offset by the proceeds of maturities of marketable securities of $252.9 million.
Cash provided by investing activities for the year ended December 31, 2024, was primarily due to proceeds from the maturities of marketable securities of $397.5 million; partially offset by purchases of marketable securities of $304.4 million, purchases of property and equipment of $4.9 million, and payments to acquire in-process research and development of $1.6 million.
The increase primarily relates to an increase of $10.7 million in interest income earned from marketable securities in 2023. Income Tax An income tax expense of $0.2 million was recognized for the year ended December 31, 2023, which was primarily related to deferred state taxes.
An income tax expense of $0.2 million was recognized for the year ended December 31, 2023, which was primarily related to deferred state taxes.
External costs include: • costs associated with acquiring technology and intellectual property licenses that have no alternative future uses, sublicensing revenues, and milestones; • costs incurred in connection with the preclinical and clinical development and manufacturing of our product candidates, including under agreements CMOs, suppliers, clinical research organizations (“CROs”), and clinical sites; and • other research and development costs, including laboratory materials and supplies, and consulting services. 110 Table of Contents Internal costs include: • personnel-related costs, including salaries, benefits, and share-based compensation expense, for our research and development personnel; and • allocated facilities and other overhead expenses, including expenses for rent, facilities maintenance, and depreciation.
External costs include: • costs associated with acquiring technology and intellectual property licenses that have no alternative future uses, sublicensing revenues, and milestones; • costs incurred in connection with the preclinical and clinical development and manufacturing of our product candidates, including under agreements with CMOs, suppliers, clinical research organizations (“CROs”), and clinical sites; and • other research and development costs, including laboratory materials and supplies, and consulting services.
We recognized a gain related to the change in the fair value of the MSKCC success payments liability in the amount of $2.4 million for the year ended December 31, 2022. We recognized a $10.7 million increase in other income during the year ended December 31, 2023 compared to December 31, 2022.
Total Other Income Total other income increased by $3.3 million for the year ended December 31, 2024, as compared to the year ended December 31, 2023. We recognized a gain related to the change in the fair value of the MSKCC success payments liability in the amount of $2.2 million for the year ended December 31, 2024.
Our genome-editing platform, including our novel chRDNA ( C RISPR h ybrid R NA- DNA , or “chRDNA,” pronounced “chardonnay”) technology, enables more precise genome editing to develop cell therapies that are armored to improve activity against diseases.
Our genome-editing platform, including our novel chRDNA ( C RISPR h ybrid R NA- DNA , or “chRDNA,” pronounced “chardonnay”) technology, enables more precise genome editing of allogeneic cell therapies.
As of December 31, 2023, the satisfaction and timing of such contingent payments is uncertain and is not reasonably estimable. We have milestones, royalties, and/or other payments due to third parties under our existing license and assignment agreements. See Note 9 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
We have milestones, royalties, and/or other payments due to third parties under our existing license and assignment agreements. See Note 9 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
Cash used in operating activities in the year ended December 31, 2022 was primarily due to our net loss of $99.4 million, adjusted by non-cash charges of $12.7 million and net changes in our net operating assets and liabilities of $4.2 million.
Cash used in operating activities in the year ended December 31, 2024, was primarily due to our net loss of $149.1 million, adjusted by non-cash charges of $16.0 million and net changes in our net operating assets and liabilities of $5.1 million.
If we raise additional capital through debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends. If we raise additional capital through the sale of equity or convertible debt securities, the issuance of these securities could result in dilution to our stockholders.
If we raise additional capital through debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, or declaring dividends.
Based on our current operating plan, we expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our current operating plan for at least the next 12 months from the date of this Annual Report on Form 10-K.
Funding Requirements We expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our current operating plan for at least the next 12 months from the date this Annual Report on Form 10-K is filed. We have based these estimates on our current assumptions, which may require future adjustments based on our ongoing business decisions.
MSKCC Agreement Success Payments Under the MSKCC Agreement, we are obligated to make success payments to MSKCC of up to $35.0 million if our stock price increases by certain multiples of increasing value based on a comparison of the fair market value of our common stock with $5.1914 per share, adjusted for future stock splits, during a specified time period.
We cannot estimate when such payments will be due and none of these events is probable as of December 31, 2024. 107 Tabl e of Contents MSKCC Agreement Success Payments Under the MSKCC Agreement, we are obligated to make success payments to MSKCC of up to $35.0 million if our stock price increases by certain multiples of increasing value based on a comparison of the fair value of our common stock with $5.1914 per share, adjusted for future stock splits, during a specified time period.
The following table summarizes our revenue by licensee for the years ended December 31, 2023 and 2022: Years Ended December 31, 2023 2022 Change (in thousands) AbbVie $ 24,802 $ 7,956 $ 16,846 Edge Animal Health, related party 1,150 — 1,150 Pfizer, related party 1,243 — 1,243 Other licensees 7,282 5,895 1,387 Total licensing and collaboration revenue $ 34,477 $ 13,851 $ 20,626 Research and Development Expenses Research and development expenses increased by $29.8 million to $112.1 million for the year ended December 31, 2023 from $82.2 million for the year ended December 31, 2022.
The following table summarizes our revenue by licensee for the years ended December 31, 2024, and 2023: Years Ended December 31, 2024 2023 Change (in thousands) AbbVie $ — $ 24,802 $ (24,802) Edge Animal Health, related party 1,623 1,150 473 Pfizer, related party 2,487 1,243 1,244 Other licensees 5,884 7,282 (1,398) Total licensing and collaboration revenue $ 9,994 $ 34,477 $ (24,483) Research and Development Expenses Research and development expenses increased by $18.1 million to $130.2 million for the year ended December 31, 2024 from $112.1 million for the year ended December 31, 2023.
The total net proceeds from the offering were approximately $134.4 million, after deducting underwriting discounts and commissions and offering expenses. The shares were sold under the Shelf Registration Statement. As of December 31, 2023, we had cash, cash equivalents, and marketable securities of $372.4 million.
The total net proceeds from the offering were approximately $134.4 million, after deducting underwriting discounts and commissions and offering expenses. The shares were sold under the Shelf Registration Statement.
We recognized a loss related to the change in the fair value of the MSKCC success payments liability in the amount of $1.3 million for the year ended December 31, 2023.
We recognized a loss related to the change in the fair value of the MSKCC success payments liability in the amount of $1.3 million for the year ended December 31, 2023. Income Tax An income tax benefit of less than $0.1 million was recognized for the year ended December 31, 2024, which was primarily related to deferred state taxes.
On August 9, 2022, we filed a universal shelf registration statement on Form S-3 (“Shelf Registration Statement”) with the SEC, which allows us to, from time to time, sell up to $400.0 million of common stock, preferred stock, debt securities, warrants, rights, or units comprised of any combination thereof (including the $100.0 million of common stock reserved for our at-the-market equity offering program described below).
Securities and Exchange Commission (“SEC”), which allows us to, from time to time, sell up to $400.0 million of common stock, preferred stock, debt securities, warrants, rights, or units comprised of any combination thereof (including the $100.0 million of common stock reserved for our at-the-market equity offering program described below).
Revenue for the material right for license renewals is recognized at the point in time the annual license fee is paid by the licensee and the renewal period begins. Our collaboration and license agreements may include contingent milestone payments. Such milestone payments are typically payable when the collaboration partner or licensee achieves certain predetermined clinical, regulatory, and/or commercial milestones.
Revenue for the material right for license renewals is recognized at the point in time the annual license fee is paid by the licensee and the renewal period begins. 110 Tabl e of Contents Our collaboration and license agreements may include contingent milestone payments.
In February 2024, we sold 1,594,171 shares of our common stock under the ATM Sales Agreement, at an average price per share of $7.33 for aggregate gross proceeds of $11.7 million ($11.3 million, net of offering expenses).
Through December 31, 2024, we sold an aggregate of 3,588,696 shares of our common stock under the ATM Sales Agreement at an average price per share of $4.71 for aggregate gross proceeds of $16.9 million ($16.2 million net of offering expenses).
Milestone payments that are not within our or the licensee’s control, such as regulatory approvals, are not considered probable of being achieved until those approvals are received. At each reporting date, we re-evaluate whether the milestones are considered probable of being achieved and estimate the amount to be included in the transaction price by using the most likely amount method.
At each reporting date, we re-evaluate whether the milestones are considered probable of being achieved and estimate the amount to be included in the transaction price by using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price in such period of determination.
Other Income (Expense) Other income (expense) consists primarily of interest income earned on cash and marketable securities and the change in fair value of the Memorial Sloan Kettering Cancer Center (“MSKCC”) success payments liability under our Exclusive License Agreement, dated November 13, 2020 with MSKCC (“MSKCC Agreement”). 112 Table of Contents Results of Operations Comparison of the Years Ended December 31, 2023 and 2022 The following table summarizes our results of operations for the periods indicated: Years Ended December 31, Change 2023 2022 $ (in thousands) Licensing and collaboration revenue $ 34,477 $ 13,851 $ 20,626 Operating expenses Research and development 112,075 82,230 29,845 General and administrative 38,461 38,020 441 Total operating expenses 150,536 120,250 30,286 Loss from operations (116,059) (106,399) (9,660) Other income (expense) Change in fair value of equity securities (6) (133) 127 Change in fair value of the MSKCC success payments liability (1,288) 2,429 (3,717) Other income, net 15,476 4,752 10,724 Total other income 14,182 7,048 7,134 Net loss before provision for income taxes (101,877) (99,351) (2,526) Provision for income taxes 193 70 123 Net loss $ (102,070) $ (99,421) $ (2,649) Licensing and Collaboration Revenue Licensing and collaboration revenue increased by $20.6 million to $34.5 million for the year ended December 31, 2023 from $13.9 million for the year ended December 31, 2022.
Other Income (Expense) Other income (expense) consists primarily of interest income earned on cash and marketable securities and the change in fair value of the Memorial Sloan Kettering Cancer Center (“MSKCC”) success payments liability under our Exclusive License Agreement, dated November 13, 2020, with MSKCC (as amended, “MSKCC Agreement”). 103 Tabl e of Contents Results of Operations Comparison of the Years Ended December 31, 2024, and 2023 The following table summarizes our results of operations for the periods indicated: Years Ended December 31, Change 2024 2023 $ (in thousands) Licensing and collaboration revenue $ 9,994 $ 34,477 $ (24,483) Operating expenses: Research and development 130,153 112,075 18,078 General and administrative 46,457 38,461 7,996 Total operating expenses 176,610 150,536 26,074 Loss from operations (166,616) (116,059) (50,557) Other income (expense) Change in fair value of the MSKCC success payments liability 2,154 (1,288) 3,442 Other income, net 15,348 15,470 (122) Total other income 17,502 14,182 3,320 Net loss before (benefit from) provision for income taxes (149,114) (101,877) (47,237) (Benefit from) provision for income taxes (9) 193 (202) Net loss $ (149,105) $ (102,070) $ (47,035) Licensing and Collaboration Revenue Licensing and collaboration revenue decreased by $24.5 million to $10.0 million for the year ended December 31, 2024, from $34.5 million for the year ended December 31, 2023.
If our development efforts for our product candidates are successful and result in regulatory approval and commercialization, we may generate revenue in the future from product sales. We cannot predict if, when, or to what extent we will generate revenue from the commercialization and sale of our product candidates if we succeed in obtaining regulatory approval for these product candidates.
We cannot predict if, when, or to what extent we will generate revenue from the commercialization and sale of our product candidates if we succeed in obtaining regulatory approval for these product candidates. To date, all of our revenue consists of licensing and collaboration revenue earned from collaboration and/or licensing agreements entered into with third parties, including related parties.
Cash Used in Investing Activities During the year ended December 31, 2023 and 2022, cash used in investing activities was $68.2 million and $93.2 million, respectively.
Cash Provided by (Used in) Investing Activities Net cash provided by investing activities was $86.6 million for the year ended December 31, 2024. Net cash used in investing activities was $68.2 million for the year ended December 31, 2023.
We make significant judgments and estimates in determining the accrual balance in each reporting period. As actual costs become known, we adjust our accruals.
We accrue for these costs based on factors such as estimates of the work completed and in accordance with service agreements established with these third-party service providers. We make significant judgments and estimates in determining the accrual balance in each reporting period. As actual costs become known, we adjust our accruals.
Sales-based milestones are recognized at the later of when the associated performance obligation has been satisfied or when the sales occur. Unlike other contingency payments, such as regulatory milestones, sales-based milestones are not included in the transaction price based on estimates at the inception of the contract, but rather, are included when the sales or usage occur.
Unlike other contingency payments, such as regulatory milestones, sales-based milestones are not included in the transaction price based on estimates at the inception of the contract, but rather, are included when the sales or usage occur. Accrued Research and Development Expenses As part of the process of preparing our financial statements, we are required to estimate and accrue expenses.
Interest and penalties related to unrecognized tax benefits are included within the provision for income tax. Recently Issued Accounting Pronouncements See Note 2 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for more information regarding recently issued accounting pronouncements.
Recently Issued Accounting Pronouncements See Note 2 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for more information regarding recently issued accounting pronouncements. Emerging Growth Company and Smaller Reporting Company Status We are an emerging growth company, as defined in the Jumpstart Our Business Startups Act of 2012 Act (“JOBS Act”).
If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price in such period of determination. Our collaboration and license agreements may also include contingent payments related to sales-based milestones. Sales-based milestones are typically payable when annual sales of a covered product reach specified levels.
Our collaboration and license agreements may also include contingent payments related to sales-based milestones. Sales-based milestones are typically payable when annual sales of a covered product reach specified levels. Sales-based milestones are recognized at the later of when the associated performance obligation has been satisfied or when the sales occur.
These increases were partially offset by a $0.4 million decrease in expenses related to licenses, sublicensing revenue, and milestones. General and Administrative Expenses General and administrative expenses increased by $0.4 million to $38.5 million for the year ended December 31, 2023 from $38.0 million for the year ended December 31, 2022.
General and Administrative Expenses General and administrative expenses increased by $8.0 million to $46.5 million for the year ended December 31, 2024, from $38.5 million for the year ended December 31, 2023.
We separately track certain external costs on a program-by-program basis; however, we do not track costs that are deployed across multiple programs. Research and development activities are central to our business model.
We do not allocate internal costs as several of our departments support multiple programs and our payroll and other personnel expenses are not tracked on a program-by-program basis. Research and development activities are central to our business model.
Accrued Research and Development Expenses As part of the process of preparing our financial statements, we are required to estimate and accrue expenses. Research and development expenses are charged to expense as incurred. Research and development expenses include those for certain payroll and personnel; laboratory supplies; consulting; manufacturing; external clinical; and allocated overhead, including rent, equipment depreciation, and utilities.
Research and development expenses are expensed as incurred. Research and development expenses include those for certain payroll and personnel; laboratory supplies; consulting; manufacturing; external clinical; and allocated overhead, including rent, equipment depreciation, and utilities. We record accrued liabilities for estimated costs of research and development activities conducted by third-party CMOs, CROs, and other third-party service providers.
These agreements provide for termination at the request of either party generally with less than one-year notice and, therefore, we believe that our non-cancelable obligations under these agreements are not material. Some of these agreements include contingent payments that will become payable if and when we achieve certain development, regulatory, clinical, and/or commercial milestones.
Contractual Obligations and Commitments We enter into contracts in the normal course of business with suppliers, CMOs, CROs, clinical trial sites, licensors, assignors, and the like. These agreements provide for termination at the request of either party generally with less than one-year’s notice and, therefore, we believe that our non-cancelable obligations under these agreements are not material.
Additionally, we agreed to provide Pfizer access to any preclinical or interim or final clinical data (including raw data) and results generated as part of the development program for a BCMA Product Candidate at the same time that we provide such data to a third party (other than to our service providers or the FDA or other regulatory authorities), subject to certain confidentiality exceptions.
Additionally, we agreed to provide Pfizer access to any preclinical or interim or final clinical data (including raw data) and results generated as part of the development program for a BCMA Product Candidate at the same time that we provide such data to a third party (other than to our service providers or the FDA or other regulatory authorities), subject to certain confidentiality exceptions. 108 Tabl e of Contents Cash Flows Comparison of the Years Ended December 31, 2024, and 2023 The following table summarizes our cash flows for the periods indicated: Years Ended December 31, 2024 2023 Change (in thousands) Cash used in operating activities $ (138,200) $ (93,291) $ (44,909) Cash provided by (used in) investing activities 86,607 (68,183) 154,790 Cash provided by financing activities 16,724 154,298 (137,574) Net decrease in cash, and cash equivalents, and restricted cash $ (34,869) $ (7,176) $ (27,693) Cash Used in Operating Activities Net cash used in operating activities was $138.2 million and $93.3 million for the years ended December 31, 2024, and 2023, respectively.
Since our founding in 2011, we have devoted substantially all of our resources to organizing and staffing, business planning, raising capital, expanding our genome-editing platform technologies, developing our product candidates and building our pipeline, creating and maintaining our intellectual property portfolio, and establishing arrangements with third parties for the manufacture, testing, and clinical trial evaluations of our product candidates.
We are advancing our pipeline of allogeneic CAR-T cell therapies with the following four clinical development programs targeting the treatment of hematologic malignancies and autoimmune diseases: • CB-010: an allogeneic anti-CD19 CAR-T cell therapy, being evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (“r/r B-NHL”) in our ANTLER phase 1 clinical trial • CB-010: also being evaluated in patients with lupus nephritis (“LN”) and in patients with extrarenal lupus (“ERL”) in our GALLOP phase 1 clinical trial • CB-011: an allogeneic anti-BCMA CAR-T cell therapy, being evaluated in patients with relapsed or refractory multiple myeloma (“r/r MM”) in our CaMMouflage phase 1 clinical trial • CB-012: an allogeneic anti-CLL-1 CAR-T cell therapy, being evaluated in patients with relapsed or refractory acute myeloid leukemia (“r/r AML”) in our AMpLify phase 1 clinical trial Since our founding in 2011, we have devoted substantially all of our resources to organizing and staffing, business planning, raising capital, expanding our genome-editing platform technologies, developing our product candidates and building our pipeline, creating and maintaining our intellectual property portfolio, and establishing arrangements with third parties for the manufacture, testing, and clinical trial evaluations of our product candidates.
Cash provided by financing activities for the year ended December 31, 2022 was due to the exercise of stock options and purchases of common stock under the 2021 Employee Stock Purchase Plan of $2.1 million.
Cash Provided by Financing Activities Net cash provided by financing activities was $16.7 million and $154.3 million for the years ended December 31, 2024, and 2023, respectively. 109 Tabl e of Contents Cash provided by financing activities for the year ended December 31, 2024, was primarily due to net proceeds from our at-the-market equity offering program of $15.2 million, the issuances of common stock under the 2021 Employee Stock Purchase Plan (“ESPP”) of $0.9 million, and the exercises of stock options of $0.6 million.
If we raise additional capital through marketing and distribution arrangements or other collaborations, strategic alliances, or licensing arrangements with third parties or other sources, we may have to relinquish certain valuable rights to our product candidates, technologies, future revenue streams, or research programs or grant licenses on terms that may not be favorable to us. 117 Table of Contents Cash Flows Comparison of the Years Ended December 31, 2023 and 2022 The following table summarizes our cash flows for the periods indicated: Years Ended December 31, 2023 2022 Change (in thousands) Cash used in operating activities $ (93,291) $ (90,966) $ (2,325) Cash used in investing activities (68,183) (93,249) 25,066 Cash provided by financing activities 154,298 2,133 152,165 Net decrease in cash and cash equivalents $ (7,176) $ (182,082) $ 174,906 Cash Used in Operating Activities Net cash used in operating activities was $93.3 million and $91.0 million for the years ended December 31, 2023 and 2022, respectively.
If we raise additional capital through marketing and distribution arrangements or other collaborations, strategic alliances, or licensing arrangements with third parties or other sources, we may have to relinquish certain valuable rights to our product candidates, technologies, future revenue streams, or research programs or grant licenses on terms that may not be favorable to us.
This increase was primarily related to an increase of $15.4 million of external CMO and CRO activities for our clinical CAR-T cell therapy product candidates, including an increase of $5.1 million due to timing of CMO activities, and $10.3 million in CRO activities for clinical 113 Table of Contents trials; $11.3 million in personnel-related expenses, including stock-based compensation, due to headcount increases; and $3.3 million in facilities and other allocated expenses.
This increase was primarily related to (i) an increase of $6.6 million in other research and development expenses to advance preclinical and clinical development for our programs, as well as other consulting services related to research and development; (ii) an increase of $4.1 million in personnel-related expenses, including an increase in salary and benefit expense of $2.5 million, an increase in stock-based compensation expense of $1.1 million, and $0.5 million of one-time expenses associated with the reduction in force that occurred during the third quarter of 2024; (iii) a net increase of $3.5 million in external CMO and CRO activities for our clinical CAR-T cell therapy product candidates, driven by (a) an increase of $9.8 million in CRO activities for clinical trials; partially offset by (b) a decrease of $6.3 million due to timing of CMO activities; (iv) an increase of $2.1 million in 104 Tabl e of Contents expenses related to licenses, sublicensing revenue, and milestones; and (v) an increase of $1.8 million in other facilities and allocated expenses.
To date, all of our revenue consists of licensing and collaboration revenue earned from collaboration and/or licensing agreements entered into with third parties, including related parties. Under these agreements, we license rights to certain intellectual property controlled by us.
Under these agreements, we license rights to certain intellectual property controlled by us.
This increase was primarily related to increases of $3.1 million in personnel-related expenses, including stock-based compensation, due to headcount increases; and $0.9 million in facilities and other allocated expenses.
This increase was primarily related to increases of $5.7 million in legal and other service-related expenses, including $3.9 million of costs related to a securities class action litigation settlement, and $2.3 million in personnel-related expenses, including an increase in salary and benefit expense of $0.4 million, an increase in stock-based compensation expense of $1.8 million, and $0.1 million of one-time expenses associated with the reduction in force that occurred during the third quarter of 2024.
We have funded our operations through sales of our capital stock, including sales of our convertible preferred stock, which generated approximately $150.1 million in aggregate net proceeds through 2021, from our initial public offering (“IPO”) in 2021, which generated approximately $321.0 million in net proceeds, and from an underwritten follow-on public offering in 2023 which generated approximately $134.4 million in net proceeds.
Liquidity, Capital Resources, and Capital Requirements Sources of Liquidity Since our inception through December 31, 2024, we have raised an aggregate net proceeds of $836.2 million to fund our operations through our initial public offering (“IPO”); sales of convertible preferred stock; follow-on public offering; proceeds from our licensing, licensing and collaboration, service, and patent assignment agreements, including sales of Intellia stock; private placements; at-the-market equity offerings; and government grants.
The Shelf Registration Statement was declared effective by the SEC on August 16, 2022. As of December 31, 2023, we had sold securities in an aggregate amount of $144.9 million under the Shelf Registration Statement.
The Shelf Registration Statement was declared effective by the SEC on August 16, 2022, and will expire after three years.
Removed
We are advancing a pipeline of allogeneic, or off-the-shelf, cell therapies from our chimeric antigen receptor (“CAR”) T (“CAR-T”) cell and CAR-natural killer (“CAR-NK”) cell platforms as readily available therapeutic treatments for patients. We are initially focused on advancing our allogeneic cell therapies for the treatment of hematologic malignancies.
Added
Our allogeneic chimeric antigen receptor (“CAR”) -T (“CAR-T”) cell therapy product candidates are manufactured in advance with cells from healthy donors, with the goal of enabling broad patient access, rapid patient treatment, and increased manufacturing scale.
Removed
Our lead product candidate, CB-010, is an allogeneic CAR-T cell therapy that is, to our knowledge, the first anti-CD19 allogeneic, or off-the-shelf, CAR-T cell therapy to be evaluated in patients with second-line relapsed or refractory large B cell lymphoma (“r/r LBCL”).
Added
Internal costs include: • personnel-related costs, including salaries, benefits, and stock-based compensation expense, for our research and development personnel; and • allocated facilities and other overhead expenses, including expenses for rent, facilities maintenance, and depreciation. We expense research and development costs as incurred.
Removed
To our knowledge, CB-010 is also the first clinical-stage allogeneic anti-CD19 CAR-T cell therapy with programmed cell death protein 1 (“PD-1”) removed from the CAR-T cell surface by a genome-edited knockout of the PDCD1 gene. CB-010 is being evaluated in our ongoing ANTLER phase 1 clinical trial in adult patients with r/r B-NHL.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

2 edited+0 added−0 removed3 unchanged
Biggest changeWe had cash, cash equivalents, and marketable securities of $372.4 million as of December 31, 2023, consisting of cash, money market funds, government securities, commercial paper, and corporate debt securities, and we had cash and cash equivalents of $317.0 million as of December 31, 2022, consisting of cash, money market funds, government securities, commercial paper, and corporate debt securities.
Biggest changeWe had cash, cash equivalents, and marketable securities of $249.4 million as of December 31, 2024, consisting of cash, money market funds, government securities, commercial paper, and corporate debt securities, and we had cash and cash equivalents of $372.4 million as of December 31, 2023, consisting of cash, money market funds, government securities, commercial paper, and corporate debt securities.
We do not believe that inflation had a material effect on our results of operations during the year ended December 31, 2023.
We do not believe that inflation had a material effect on our results of operations during the year ended December 31, 2024.

Other CRBU 10-K year-over-year comparisons