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Caribou Biosciences, Inc.

Caribou Biosciences, Inc.CRBU決算レポート

Nasdaq · ヘルスケア · 生物製品（診断物質を含まない）

Caribou Biosciences, Inc. is a clinical-stage biotechnology company focused on developing CRISPR genome-edited cell therapies for cancers and autoimmune diseases. It operates mainly in North American and European markets, partnering with leading pharmaceutical enterprises to advance its pipeline of accessible, targeted therapeutic products for global patients.

What changed in Caribou Biosciences, Inc.'s 10-K — 2024 vs 2025

Top changes in Caribou Biosciences, Inc.'s 2025 10-K

813 paragraphs added · 850 removed · 608 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

216 edited+55 added−124 removed165 unchanged
Failure to comply with the applicable requirements at any time during the product development process, including nonclinical testing, clinical testing, the approval process, or post-approval process, may subject us to delays in the conduct of a clinical trial, regulatory review and approval, and/or subject us to administrative or judicial sanctions.
Failure to comply with the applicable requirements at any time during the product development process, including nonclinical testing, clinical testing, the approval process, or post-approval process, may subject us to delays in the conduct of a clinical trial, delays in regulatory review and approval, and/or administrative or judicial sanctions.
An IND is an exemption from the restrictions of the FDCA, which would otherwise preclude an unapproved biologic product candidate from being shipped in interstate commerce. Under a cleared IND, the unapproved biologic product candidate may be shipped in interstate commerce for use in an investigational clinical trial, provided that the product candidate meets certain quality and labeling requirements.
An IND is an exemption from the restrictions of the FDCA, which would otherwise preclude an unapproved biologic candidate from being shipped in interstate commerce. Under a cleared IND, the unapproved biologic candidate may be shipped in interstate commerce for use in an investigational clinical trial, provided that the product candidate meets certain quality and labeling requirements.
The BLA must contain sufficient manufacturing information and detailed information on the composition of the product candidate and proposed labeling as well as payment of a user fee, unless the criteria for a waiver or exemption are met.
A BLA must contain sufficient manufacturing information and detailed information on the composition of the product candidate and proposed labeling as well as payment of a user fee, unless the criteria for a fee waiver or exemption are met.
Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting adverse reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation.
Significant improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or substantial reduction of a treatment-limiting adverse reaction, documented enhancement of patient compliance that may lead to improvement in serious outcomes, or evidence of safety and effectiveness in a new subpopulation.
Patent Term Extension A patent claiming a new biologic product may be eligible for a limited PTE under the Hatch-Waxman Amendments, which permits a patent restoration of up to five years for patent term lost during product development and FDA regulatory review.
Patent Term Extension A patent claiming a new biologic may be eligible for a limited PTE under the Hatch-Waxman Amendments, which permits a patent restoration of up to five years for patent term lost during product development and FDA regulatory review.
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.
To date, we have entered into over 30 sublicensing agreements in a variety of fields such as human therapeutics, animal therapeutics, agriculture, forestry, 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.
Unless otherwise required by regulation, the pediatric data requirements do not apply to products with orphan designation except a product with a new active ingredient that is a molecularly targeted cancer product intended for the treatment of an adult cancer and directed at a molecular target determined by the FDA to be substantially relevant to the growth or progression of a pediatric cancer.
Unless otherwise required by regulation, the pediatric data requirements do not apply to products with orphan drug designation except a product with a new active ingredient that is a molecularly targeted cancer product intended for the treatment of an adult cancer and directed at a molecular target determined by the FDA to be substantially relevant to the growth or progression of a pediatric cancer.
Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the product from the market on an expedited basis. All promotional materials for product candidates approved under accelerated regulations are subject to prior review by the FDA unless the FDA informs us otherwise.
Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the product from the market on an expedited basis. All promotional materials for product candidates approved under accelerated approval are subject to prior review by the FDA unless the FDA informs us otherwise.
Our CaMMouflage phase 1 clinical trial is being conducted in two parts: Part A is dose escalation following a standard 3 + 3 design, with sequential, increasing single doses of CB-011 with the ability to add additional patients at safe dose levels to further evaluate activity and safety.
Our CaMMouflage phase 1 clinical trial is being conducted in two parts: Part A was the dose escalation part following a standard 3 + 3 design, with sequential, increasing single doses of CB-011 with the ability to add additional patients at safe dose levels to further evaluate activity and safety.
Under the goals agreed to by the FDA under the Prescription Drug User Fee Act (“PDUFA”), for a new molecular entity, the FDA has 10 months from date that the FDA filed the BLA in which to complete its initial review of a standard application and respond to us, and six months from such filing date for a priority review of the application.
Under the goals agreed to by the FDA under the Prescription Drug User Fee Act (“PDUFA”), for a new molecular entity, the FDA has 10 months from the date that BLA is filed in which to complete its initial review of a standard application and respond to us, and six months from such filing date for a priority review of the application.
In January 2025, the FDA removed its June 2024 guidance on clinical trial diversity action plans from its website, and it is not clear how the FDA will enforce the statutory requirement under FDORA.
In January 2025, the FDA removed its June 2024 draft guidance on clinical trial diversity action plans from its website, and it is not clear how the FDA will enforce the statutory requirement under FDORA.
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.
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 a drug or biologic, methods of use, or methods of manufacturing may be restored.
Restrictions under applicable U.S. federal and state healthcare laws and regulations, as well as equivalent international laws, include but are not limited to the following: • the U.S. federal Anti-Kickback Statute (“AKS”), which prohibits, among other things, individuals or entities from knowingly and willfully soliciting, receiving, offering or paying any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce, or reward, either the referral of an individual, or the purchase, lease, order, arrangement for or recommendation of the purchase, lease, order, arrangement for any good, facility, item, or service, for which payment may be made, in whole or in part, under a federal healthcare program, such as Medicare and Medicaid; • the U.S. civil and criminal false claims laws, including the civil U.S.
Restrictions under applicable U.S. federal and state healthcare laws and regulations, as well as equivalent international laws, include but are not limited to the following: • the U.S. federal Anti-Kickback Statute (“AKS”), which prohibits, among other things, individuals or entities from knowingly and willfully soliciting, receiving, offering or paying any remuneration, directly or indirectly, overtly or covertly, in cash or in kind, to induce, or reward, either the referral of an individual, or the purchase, lease, order, arrangement for or recommendation of the purchase, lease, order, arrangement for any good, facility, item, or service, for which payment may be made, in whole or in part, under a federal healthcare program, such as Medicare and Medicaid; 32 Table of Contents • the U.S. civil and criminal false claims laws, including the civil U.S.
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.
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.
United States Even if any product candidates we may develop obtain approval, sales of such product candidates will depend, in part, on the extent to which third-party payors, including government healthcare programs in the United States, such as Medicare and Medicaid, commercial health insurers, and managed care organizations provide coverage and establish adequate reimbursement levels for such product candidates.
United States Even if any product candidates we may develop obtain regulatory approval, sales of such products will depend, in part, on the extent to which third-party payors, including government healthcare programs in the United States, such as Medicare and Medicaid, commercial health insurers, and managed care organizations provide coverage and establish adequate reimbursement levels for such products.
The FDA will not approve a BLA unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to ensure consistent production of the product within required specifications. The PHSA emphasizes the importance of manufacturing control for products such as biologics whose attributes cannot be precisely defined.
The FDA will not approve a BLA unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to ensure consistent production of the product within required specifications. The PHSA emphasizes the importance of manufacturing controls for products such as biologics whose attributes cannot be precisely defined.
Like Cas9, Cas12a is a Cas protein used to edit genomic DNA site-specifically. The advantages of our chRDNA technologies include: • Specificity: Our chRDNA guides mediate higher genome-editing specificity as compared to all-RNA guides. Significantly fewer off-target events are observed using our chRDNA guides versus first-generation CRISPR-Cas9 or CRISPR-Cas12a systems using all-RNA guides.
Like Cas9, Cas12a is a Cas protein used to edit genomic DNA site-specifically. The advantages of our chRDNA technology include: • Specificity: Our chRDNA guides mediate higher genome-editing specificity as compared to all-RNA guides. Significantly fewer off-target events are observed using our chRDNA guides versus first-generation CRISPR-Cas9 or CRISPR-Cas12a systems using all-RNA guides.
Although we believe that our scientific expertise, novel technologies, and intellectual property position offer competitive advantages, we face competition from multiple other genome-editing technologies and companies. Other companies developing CRISPR-based technologies include, among others, Arbor Biotechnologies, Inc., Beam Therapeutics Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., Intellia Therapeutics, Inc., Mammoth Biosciences, Inc., Metagenomi, Inc., and Scribe Therapeutics, Inc.
Although we believe that our novel technologies and intellectual property position offer competitive advantages, we face competition from multiple other genome-editing technologies and companies. Other companies developing CRISPR-based technologies include, among others, Arbor Biotechnologies, Inc., Beam Therapeutics Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., Intellia Therapeutics, Inc., Mammoth Biosciences, Inc., Metagenomi Therapeutics, Inc., and Scribe Therapeutics, Inc.
Many of our competitors, either alone or with their collaborators, have substantially greater financial, technical, and other resources, such as larger research and development staff, and/or greater expertise in research and development, preclinical testing, conducting clinical trials, established manufacturing capabilities and facilities, and experienced marketing organizations with well-established sales forces.
Many of our competitors, either alone or with their collaborators, have substantially greater financial, technical, and other resources, such as larger research and development staff, and/or greater expertise in research and development, nonclinical testing, conducting clinical trials, established manufacturing capabilities and facilities, and experienced marketing organizations with well-established sales forces.
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.
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 financial disclosure requirements; 21 Table of Contents • preparation and submission to the FDA of a biologics license application (“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; • 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 a BLA; • payment of any user fees and securing FDA approval of a 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.
The FDA, the applicable IRB, or we may suspend or terminate a clinical trial at any time for various reasons, including a finding that the clinical trial is not being conducted in accordance with FDA requirements or that the subjects or patients are being exposed to an unacceptable health risk.
The FDA, the applicable IRB, or we may suspend or terminate a clinical trial, in whole or in part, at any time for various reasons, including a finding that the clinical trial is not being conducted in accordance with FDA requirements or that the subjects or patients are being exposed to an unacceptable health risk.
However, the FDA’s goal for reviewing a rolling submission does not begin until the last section of the application is submitted.
However, the FDA’s goal timeline for reviewing a rolling submission does not begin until the last section of the application is submitted.
Relevant regulatory authorities include, but are not limited to, the FDA; the European Medicines Agency (“EMA”), an agency of the European Union (“EU”) in charge of the evaluation and supervision of medicinal products; the European Commission, which is the executive arm of the EU; and other national, state, local, and provincial regulatory authorities.
Relevant regulatory authorities include, but are not limited to, the FDA; the European Medicines Agency (“EMA”), an agency of the EU in charge of the evaluation and supervision of medicinal products; the European Commission, which is the executive arm of the EU; and other national, state, local, and provincial regulatory authorities.
When the sponsor submits a response to the issues identified in the hold letter, the FDA must respond in writing to the sponsor within 30 days of the complete response by either removing or maintaining the clinical hold. The FDA may impose a partial or full clinical hold with respect to our product candidate.
When the sponsor submits a response to the issues identified in the hold letter, the FDA should respond in writing to the sponsor within 30 days of the complete response by either removing or maintaining the clinical hold. The FDA may impose a partial or full clinical hold with respect to our product candidate.
Additionally, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved, and inadequate reimbursement rates, including significant patient cost sharing obligations, may deter patients from selecting our product candidates.
Additionally, a payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be approved, and inadequate reimbursement rates, including significant patient cost sharing obligations, may deter patients from selecting our products.
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).
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 technology (which, for granted U.S. patents, without PTA or PTE, will expire in 2036).
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.
Our culture is built around our core values: we are driven by patient need, 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.
The FDA may also grant accelerated approval for such a condition when our product candidate has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality (“IMM”), and that our product candidate is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition, and the availability or lack of alternative treatments.
The FDA may also grant accelerated approval when our product candidate has an effect on an intermediate clinical endpoint that can be measured earlier than an effect on irreversible morbidity or mortality (“IMM”) and that is reasonably likely to predict an effect on IMM or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition, and the availability or lack of alternative treatments.
The IRA also allows HHS to directly negotiate the selling price of a statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B and Part D. The negotiated price may not exceed a statutory ceiling price.
The IRA also requires HHS to directly negotiate the selling price of a statutorily specified number of drugs and biologics each year that CMS reimburses under Medicare Part B and Part D. The negotiated price may not exceed a statutory ceiling price.
Material changes in manufacturing equipment, location, or process post-approval may result in additional regulatory review and approval.
Material changes in manufacturing equipment, location, or process post-approval may result in additional regulatory review and require approval.
The FDA may refer our BLA to an advisory committee for review, evaluation, and recommendation as to whether our BLA should be approved. In particular, the FDA may refer to an advisory committee application for biologic products that present difficult questions of safety or efficacy.
The FDA may refer our BLA to an advisory committee for review, evaluation, and recommendation as to whether our BLA should be approved. In particular, the FDA may refer to an advisory committee application for a biologic that present difficult questions of safety or efficacy.
We acquired a novel humanized single-chain variable fragment (“scFv”) directed to BCMA that we use for the generation of the BCMA-specific CAR in CB-011. To our knowledge, CB-011 is the first anti-BCMA CAR-T cell therapy incorporating an immune cloaking approach that includes both the removal of the endogenous B2M protein and insertion of a B2M–HLA-E peptide transgene.
We acquired a novel humanized single-chain variable fragment (“scFv”) directed to BCMA that we use for the generation of the BCMA-specific CAR in CB-011. To our knowledge, CB-011 is the first anti-BCMA CAR-T cell therapy incorporating an immune cloaking approach that includes both the removal of the B2M protein and insertion of a B2M–HLA-E-peptide fusion.
Allogeneic CAR-T cell therapies can be administered in academic centers of excellence and, in the future, in appropriate community hospital settings, regardless of apheresis capabilities, suggesting broader patient access to treatment. • Rapid patient treatment: Commercially available autologous CAR-T cell therapies are manufactured from the patient’s own T cells and require weeks to months for manufacturing, product release, and delivery back to the patient for treatment.
Allogeneic CAR-T cell therapies can be administered in academic centers of excellence and in appropriate community hospital settings, suggesting broader patient access to treatment. • Rapid patient treatment: Commercially available autologous CAR-T cell therapies are manufactured from the patient’s own T cells and require weeks to months for apheresis, manufacturing, product release, and delivery back to the patient for treatment.
The EU HTA Regulation 2021/2282 became effective in January 2022, is applicable from January 2025 with a phased implementation until 2030, and aims to harmonize clinical and scientific aspects of HTA across the EU. Some countries, including several EU member states, set prices and reimbursement for biological products, with limited participation from the marketing authorization holders.
The EU HTA Regulation 2021/2282 became effective in January 2022, is applicable from January 2025 with a phased implementation until 2030, and aims to harmonize clinical and scientific aspects of HTA across the EU. Some countries, including several EU member states, set prices and reimbursement for biologics, with limited participation from the marketing authorization holders.
Several healthcare reform proposals culminated in the enactment of the Inflation Reduction Act (the “IRA”) in August 2022, which, among other things, eliminated, beginning in 2025, the coverage gap under Medicare Part D by significantly lowering the enrollee maximum out-of-pocket costs and requiring manufacturers to subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs below the out-of-pocket limit, and 20% once the out-of-pocket limit has been reached.
Several healthcare reform initiatives culminated in the enactment of the Inflation Reduction Act (the “IRA”) in 2022, which, among other things, eliminated, beginning in 2025, the coverage gap under Medicare Part D by significantly lowering the enrollee maximum out-of-pocket costs and requiring manufacturers to subsidize, through a newly established manufacturer discount program, 10% of Part D enrollees’ prescription costs for brand drugs and biologics below the out-of-pocket limit, and 20% once the out-of-pocket limit has been reached.
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.
We have registered “CARIBOU,” “CARIBOU BIOSCIENCES,” “SITE-SEQ,” and the Caribou logo as trademarks in relevant classes in the United States, European Union (“EU”), and certain other jurisdictions. We also rely upon trade secrets, know-how, continuing technological innovation and potential in-licensing opportunities to develop and maintain our competitive position.
These insertions and deletions (“indels”) generally disrupt the coding sequence for the targeted gene, resulting in the knockout of the targeted sequence. HDR, by contrast, is a more controlled repair system where the cell incorporates donor DNA delivered during the experiment into the DSB, resulting in the site-specific insertion of the provided DNA sequence.
These insertions and deletions (“indels”) generally disrupt the coding sequence for the targeted gene, resulting in the knockout of the targeted sequence. HDR, by contrast, is a more controlled repair system where the cell incorporates donor DNA delivered during the editing process into the DSB, resulting in the site-specific insertion of the provided DNA sequence.
Commercially available bispecific antibodies require patients to receive frequent treatments and are associated with high infection rates. Additionally, many treatments for r/r MM are multidrug regimens comprising varying routes of administration and/or complicated dosing schedules; these regimens can be complex and burdensome for both patients and physicians.
Commercially available bispecific antibodies require patients to receive frequent treatments and are associated with high infection rates. Additionally, many treatments for r/r MM are multi-drug regimens comprising varying routes of administration and/or complicated dosing schedules; these regimens can be complex and burdensome for both patients and physicians.
A drug or biological product that has an orphan drug designation for only one rare disease or condition will be excluded from the IRA’s price negotiation requirements, but will lose that exclusion if it receives designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation.
Currently, a drug or biologic that has an orphan drug designation for only one rare disease or condition will be excluded from the IRA’s price negotiation requirements, but will lose that exclusion if it receives designations for more than one rare disease or condition, or if is approved for an indication that is not within that single designated rare disease or condition, unless such additional designation or such disqualifying approvals are withdrawn by the time CMS evaluates the drug for selection for negotiation.
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.
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 vispa-cel 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.
The process entails satisfactory completion of preclinical studies and adequate and well-controlled clinical trials to establish the safety and efficacy of a product candidate for each proposed indication.
The process entails satisfactory completion of nonclinical studies and adequate and well-controlled clinical trials to establish the safety and efficacy of a product candidate for each proposed indication.
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.
Our allogeneic, or off-the-shelf, 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.
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”)).
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, without patent term adjustment (“PTA”) or patent term extension (“PTE”)).
The FDA also will not approve the product if we are not in compliance with cGTPs, which are requirements found in FDA regulations that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues, and cellular and tissue-based products (“HCT/Ps”), which are human cells or tissue intended for implantation, transplant, infusion, or transfer into a human recipient.
The FDA also will not approve a product if our manufacturing is not in compliance with cGTPs, which are requirements found in FDA regulations that govern the methods used in, and the facilities and controls used for, the manufacture of human cells, tissues, and cellular and tissue-based products (“HCT/Ps”), which are human cells or tissue intended for implantation, transplant, infusion, or transfer into a human recipient.
If we wish to conduct a clinical trial outside of the United States, we may, but need not, obtain FDA authorization to conduct the clinical trial under an IND application. When a foreign clinical trial is conducted under a foreign equivalent to an IND application, FDA IND applications requirements must be met unless waived.
If we wish to conduct a clinical trial outside of the United States, we may, but need not, obtain FDA authorization to conduct the clinical trial under an IND. When a foreign clinical trial is conducted under an IND, FDA IND requirements must be met unless waived.
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.
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 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.
Genome-Editing Strategies for Allogeneic CAR-T Cell Therapies CAR-T cells will generally proliferate in response to antigen engagement via the specificity of their respective CAR. However, allogeneic CAR-T cells are rapidly rejected by a patient’s immune system due to their divergent donor-derived genetic profile and cell surface HLA presentation.
Genome-Editing Strategies for Allogeneic CAR-T Cell Therapies CAR-T cells will generally proliferate in response to antigen engagement via the specificity of their respective CAR. However, allogeneic CAR-T cells are rapidly rejected by a patient’s immune system due to their divergent donor-derived genetic profile and cell surface human leukocyte antigen (“HLA”) presentation.
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).
Additionally, we will owe Intellia low- to mid- single-digit percent royalties on net sales of our vispa-cel 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 a drug becomes the first drug that is approved for the same indication for which the FDA has granted the designation, the drug will be entitled to exclusivity, which means the FDA may not approve any other application to market the same drug for the same orphan indication for a period of seven years following the date of our product’s marketing approval, except in certain circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity by means of greater effectiveness, greater safety, or providing a major contribution to patient care, or in instances of drug supply issues.
If a drug or biologic becomes the first product that is approved for the same disease or condition for which the FDA has granted the designation, that product will be entitled to orphan drug exclusivity, which means the FDA may not approve any other application to market the same drug or biologic for the same orphan disease or condition for a period of seven years following the date of marketing approval, except in certain circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity by means of greater effectiveness, greater safety, or providing a major contribution to patient care, or in instances of product supply issues.
Breakthrough therapy designation may be rescinded if our product candidate no longer meets the qualifying criteria. The FDA may determine that an application will receive priority review designation if the application is for a product candidate that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.
Breakthrough therapy designation may be rescinded if our product candidate no longer meets the qualifying criteria. 26 Table of Contents The FDA may determine that an application will receive priority review designation if the application is for a product candidate that treats a serious condition and, if approved, would provide a significant improvement in safety or effectiveness.
As a result, obtaining coverage and reimbursement approval for such a product from a government or other third-party payor is a time-consuming and costly process that could require us to provide to each payor supporting scientific, clinical, and cost-effectiveness data regarding the product’s clinical benefits, medical necessity, and risks on a payor-by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained.
As a result, obtaining coverage and reimbursement approval for such a product from a government or other third-party payor is a time-consuming and costly process that could require us to provide to each payor supporting scientific, clinical, and cost-effectiveness data regarding the product’s clinical benefits, medical necessity, and risks on a payor-by-payor basis, and we cannot provide any assurance that coverage and adequate reimbursement will be obtained.
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.
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.
Nonclinical Studies and Investigational New Drug Applications Before testing any investigational biologic product candidate in humans, we must submit an IND application and receive clearance from the FDA to initiate a clinical trial.
Nonclinical Studies and IND Applications Before testing any investigational biologic candidate in humans, we must submit an IND application and receive clearance from the FDA to initiate a clinical trial.
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.
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 vispa-cel 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.
We require our managers and employees to play an active role in the performance management process. Our performance management 36 Tabl e of Contents process is designed to increase clarity and accountability for roles and responsibilities, strengthen communication, and build trust, all while championing personal and professional growth, learning, and success. Great teamwork is a critical foundation for Caribou.
We require our managers and employees to play an active role in the performance management process. Our performance management process is designed to increase clarity and accountability for roles and responsibilities, strengthen communication, and build trust, all while championing personal and professional growth, learning, and success. Great teamwork is a critical foundation for Caribou.
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 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 known as CB-011 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 scFv 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 expiring on June 29, 2026.
Our chRDNA technologies use the canonical Streptococcus pyogenes Cas9 protein or the Acidaminococcus sp . Cas12a protein and a guide that is composed of a mixture of RNA and DNA nucleotides in both the region that interacts with the chromosomal target DNA and in the region that does not interact with the target DNA.
Our chRDNA technology uses the canonical Streptococcus pyogenes Cas9 protein or the Acidaminococcus sp . Cas12a protein and a guide that is composed of a mixture of RNA and DNA nucleotides in both the region that interacts with the chromosomal target DNA and in the region that does not interact with the target DNA.
Some countries allow biological products to be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional testing or studies that compare the cost effectiveness of a particular biological product to currently available treatments, or so-called health technology assessments, in order to obtain reimbursement or pricing approval.
Some countries allow biologics to be marketed only after a reimbursement price has been agreed. Some countries may require the completion of additional testing or studies that compare the cost effectiveness of a particular biologic to currently available treatments, or so-called health technology assessments, in order to obtain reimbursement or pricing approval.
Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes evaluation and assessment by an IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution.
Specifically, under the NIH Guidelines, supervision of qualifying trials includes evaluation and assessment by an IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution.
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.
To our knowledge, our vispa-cel 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.
CB-011 has received fast track and orphan drug designations for r/r MM from the FDA. Target Indication We are developing CB-011 for the treatment of r/r MM. In 2024, 1.8% of all cancers were MM in the United States according to the National Cancer Institute SEER database.
CB-011 has received fast track and orphan drug designations for r/r MM from the FDA. 11 Table of Contents Target Indication We are developing CB-011 for the treatment of r/r MM. In 2025, 1.8% of all cancers in the United States were MM according to the National Cancer Institute SEER database.
Due to limited patient access and treatment burden, there is a need for an off-the-shelf, readily available, single dose treatment for patients with r/r MM. 12 Tabl e of Contents CaMMouflage Phase 1 Clinical Trial for CB-011 in r/r MM We are evaluating CB-011 in our CaMMouflage phase 1 clinical trial in adult patients with r/r MM.
Due to limited patient access and treatment burden, there is a need for an off-the-shelf, readily available, single-dose treatment for patients with r/r MM. CaMMouflage Phase 1 Clinical Trial for CB-011 in r/r MM We are evaluating CB-011 in our CaMMouflage phase 1 clinical trial in adult patients with r/r MM.
This requirement is not yet in effect as it will become applicable to all clinical trials that begin enrollment 180 days after FDA publishes its final guidance on this topic.
This requirement is not yet in effect as it will become applicable to all clinical trials that begin enrollment 180 days after FDA publishes its final guidance on this topic. The final guidance has not yet been published.
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.
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.
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.
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. 15 Table of Contents Pioneer Hi-Bred International, Inc.
We have made a significant investment in process development to control our product candidate characteristics and to also improve our supply chain capabilities. For the manufacturing of our allogeneic CAR-T cell therapy product candidates, we have developed a platform process that is scaled to eventually support commercially manufacturing.
We have made a significant investment in process development to optimize and control our product candidate characteristics and to also improve our supply capabilities. For the manufacturing of our allogeneic CAR-T cell therapy product candidates, we have developed a platform process that is scaled to support commercial manufacturing.
Patients are unlikely to use any product candidates we may develop unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of such product candidates. In addition, direct or indirect governmental price regulation may affect the prices that we may charge for product candidates.
Patients are unlikely to use any products we may develop unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of our products. In addition, direct or indirect governmental price regulation may affect the prices that we may charge for our products.
Our ANTLER phase 1 clinical trial consists of two parts: Part A was the dose escalation portion that followed a standard 3 + 3 design, with sequential, increasing single doses of CB-010, and was completed with 16 patients dosed at dose level 1 (40x10 6 viable CAR-T cells), dose level 2 (80x10 6 viable CAR-T cells), or dose level 3 (120x10 6 viable CAR-T cells).
Our ANTLER phase 1 clinical trial consisted of two parts: Part A was the dose escalation portion that followed a standard 3 + 3 design, with sequential, increasing single doses of vispa-cel, and was completed with 16 patients dosed at dose level 1 (40x10 6 viable CAR-T cells), dose level 2 (80x10 6 viable CAR-T cells), or dose level 3 (120x10 6 viable CAR-T cells).
In addition, there is extensive patent infringement litigation in the biopharmaceutical industry and, in the future, we may bring or defend such litigation against our competitors. 20 Tabl e of Contents We believe that our CAR-T cell therapy product candidates have the potential to offer beneficial products to patients due to genome edits we make with our chRDNA technology with the goal of extending robust CAR-T cell activity in patients.
In addition, there is extensive patent infringement litigation in the biopharmaceutical industry and, in the future, we may bring or defend such litigation against our competitors. 18 Table of Contents We believe that, if approved, our CAR-T cell therapy product candidates have the potential to offer beneficial products to patients due to genome edits we make with our chRDNA technology with the goal of extending robust CAR-T cell activity in patients.
To date, we have successfully scaled our manufacturing processes so that one manufacturing run from a healthy donor can produce sufficient cell yield for approximately 150 doses of CB-010.This is in contrast to commercially available autologous CAR-T cell therapy where one manufacturing run is required for each patient to be treated using the patient’s cells that may have already been depleted by prior treatments and this process can take several weeks to months to deliver product for patient treatment.
To date, we have successfully scaled our manufacturing processes so that one manufacturing run from a healthy donor can produce sufficient cell yield for approximately 200-300 doses of vispa-cel and 50-100 doses for CB-011.This is in contrast to commercially available autologous CAR-T cell therapy where one manufacturing run is required for each patient to be treated using the patient’s cells that may have already been depleted by prior treatments, a process that can take several weeks to months to deliver product for patient treatment.
Only high-expenditure single-source 35 Tabl e of Contents biologics that have been approved for at least 11 years (seven years for single-source drugs) are eligible to be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.
Only high-expenditure single-source biologics that have been approved for at least 11 years (seven years for single-source drugs) are eligible to be selected by CMS for negotiation, with the negotiated price taking effect two years after the selection year.
For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced. CMS has selected 15 additional Medicare Part D drugs for negotiated maximum fair pricing in 2027.
For 2026, the first year in which negotiated prices become effective, CMS selected 10 high-cost Medicare Part D products in 2023, negotiations began in 2024, and the negotiated maximum fair price for each product has been announced.
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.
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.
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.
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 obtain regulatory approval by the FDA or other government authorities.
On June 29, 2023, in connection with the Pfizer Investment, we and Pfizer also entered into an Information Rights Agreement, having a thirty-six (36)-month term.
On June 29, 2023, in connection with the Pfizer Investment, we and Pfizer also entered into an Information Rights Agreement, having a 36-month term and expiring on June 29, 2026.
Pediatric exclusivity is another type of non-patent marketing exclusivity in the United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing non-patent regulatory exclusivity, including orphan drug exclusivity.
Pediatric exclusivity is another type of nonpatent regulatory exclusivity for drugs and biologics in the United States and, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing nonpatent regulatory exclusivity, including orphan drug exclusivity.
We also rely on trade secrets to protect aspects of our business that are 19 Tabl e of Contents not amenable to, or that we do not consider appropriate for, patent protection.
We also rely on trade secrets to protect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection.
Autologous T cell therapies are being developed by a number of additional companies, including but not limited to, 2seventy bio, Inc., Adaptimmune Therapeutics PLC, Alaunos Therapeutics, Inc., Arcellx, Inc., Arsenal Biosciences, Inc., Astellas Pharma Inc., Autolus Therapeutics plc, AvenCell Therapeutics, Inc., Bristol-Myers Squibb Company, Cabaletta Bio, Inc., CARGO Therapeutics, Inc., Eureka Therapeutics, Inc., Gracell Biotechnologies Inc., an AstraZeneca PLC company, Iovance Biotherapeutics, Inc., Janssen Biotech, Inc., Kite Pharma, Inc.
Autologous T cell therapies are being developed by a number of additional companies, including but not limited to AbelZeta Pharma Inc., Arcellx, Inc., Arsenal Biosciences, Inc., Astellas Pharma Inc., Autolus Therapeutics plc, AvenCell Therapeutics, Inc., Bristol-Myers Squibb Company, Cabaletta Bio, Inc., Eureka Therapeutics, Inc., Gracell Biotechnologies Inc., an AstraZeneca PLC company, Iovance Biotherapeutics, Inc., Johnson & Johnson, Kite Pharma, Inc.
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.
Our genome-editing platform is based on our novel chRDNA ( C RISPR h ybrid R NA- DNA , or “chRDNA,” pronounced “chardonnay”) genome-editing technology, which enables more precise genome editing of allogeneic cell therapies.
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.
We have dedicated cGMP suites at our CMOs for the manufacture of our cell therapy product candidates. 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.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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If we are unable to advance our product candidates through clinical trials, obtain regulatory approval, and ultimately commercialize our product candidates, or we experience significant delays in doing so, our business will be materially harmed.
If we are unable to advance our product candidates through clinical trials, obtain regulatory approval, and ultimately commercialize our product candidates, or if we experience significant delays in doing so, our business will be materially harmed.
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.
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 therapies for cancer and other diseases.
The FDA and other regulatory authorities impose stringent restrictions on off-label promotion, and if we market our products for unapproved indications, including off-label indications, we may be subject to enforcement action for off-label marketing by the FDA and other federal and state enforcement agencies, including the DOJ.
The FDA and other regulatory authorities impose stringent restrictions on off-label promotion, and if we market our products for unapproved indications, we may be subject to enforcement action for off-label marketing by the FDA and other federal and state enforcement agencies, including the DOJ.
Other companies developing CRISPR-based technologies include, among others, Arbor Biotechnologies, Inc., Beam Therapeutics Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., Intellia Therapeutics, Inc., Mammoth Biosciences, Inc., Metagenomi, Inc., and Scribe Therapeutics, Inc. Companies developing other genome-editing technologies include, among others, Allogene Therapeutics, Inc., Cellectis S.A., Precision BioSciences, Inc., Prime Medicine, Inc., Sangamo Therapeutics, Inc., and Wave Life Sciences Ltd.
Other companies developing CRISPR-based technologies include, among others, Arbor Biotechnologies, Inc., Beam Therapeutics Inc., CRISPR Therapeutics AG, Editas Medicine, Inc., Intellia Therapeutics, Inc., Mammoth Biosciences, Inc., Metagenomi Therapeutics, Inc., and Scribe Therapeutics, Inc. Companies developing other genome-editing technologies include, among others, Allogene Therapeutics, Inc., Cellectis S.A., Precision BioSciences, Inc., Prime Medicine, Inc., Sangamo Therapeutics, Inc., and Wave Life Sciences Ltd.
We may face additional securities class action litigation, and our officers and directors may be subject to shareholder derivative suits, in the future. This risk is especially relevant for us because biotechnology and pharmaceutical companies have experienced significant stock price volatility in recent years, and we expect to experience continued stock price volatility.
In the future, we may face additional securities class action litigation, and our officers and directors may be subject to shareholder derivative suits. This risk is especially relevant for us because biotechnology and pharmaceutical companies have experienced significant stock price volatility in recent years, and we expect to experience continued stock price volatility.
We have entered into over 30 sublicenses, both exclusive and non-exclusive, to this CRISPR-Cas9 intellectual property in combination with licenses to our own Cas9 intellectual property (and sometimes in combination with a sublicense to the Vilnius Cas9 patent family we licensed from Pioneer) in a variety of fields (e.g., human therapeutics, forestry, agriculture, research reagents, transgenic animals, certain livestock targets, internal research, bioproduction, cell lines, and microbial applications, etc.).
We have entered into over 30 sublicenses, both exclusive and non-exclusive, to this CRISPR-Cas9 intellectual property in combination with licenses to our own Cas9 intellectual property (and sometimes in combination with a sublicense to the Vilnius Cas9 patent family we licensed from Pioneer) in a variety of fields (e.g., human therapeutics, animal therapeutics, agriculture, forestry, research reagents, transgenic animals, certain livestock targets, internal research, bioproduction, cell lines, and microbial applications, etc.).
Conversely, the FDA can place an IND application on clinical hold even if such other entities have provided a favorable review. In addition, regulatory agencies, including the FDA, develop and issue guidance documents with which we, in practice, must comply, even if the agencies state that the documents only represent the current thinking of the agencies and are not binding.
Conversely, the FDA can place an IND on clinical hold even if such other entities have provided a favorable review. In addition, regulatory agencies, including the FDA, develop and issue guidance documents with which we, in practice, must comply, even if the agencies state that the documents only represent the current thinking of the agencies and are not binding.
Litigation or other legal proceedings relating to intellectual property claims, with or without merit, is unpredictable and generally expensive and time-consuming and likely to divert significant resources from our core business, including distracting our management and scientific personnel from their normal responsibilities, and generally harm our business. Additionally, a defendant could counterclaim that our patent is invalid or unenforceable.
Litigation or other legal proceedings relating to intellectual property claims, with or without merit, is unpredictable and generally expensive and time-consuming and likely to divert significant resources from our core business, including distracting our management and personnel from their normal responsibilities, and generally harm our business. Additionally, a defendant could counterclaim that our patent is invalid or unenforceable.
As part of this amendment, Pioneer also granted a covenant not to sue for our licensees of our chRDNA technologies under certain other Pioneer intellectual property (to which we already have a license that, in this situation, we cannot sublicense to licensees of our chRDNA technologies in the field of human therapeutics) that might cover our chRDNA genome-editing technology, provided that we make the required payments.
As part of this amendment, Pioneer also granted a covenant not to sue for our licensees of our chRDNA technology under certain other Pioneer intellectual property (to which we already have a license that, in this situation, we cannot sublicense to licensees of our chRDNA technology in the field of human therapeutics) that might cover our chRDNA genome-editing technology, provided that we make the required payments.
These risks include: • our CMOs and suppliers may be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our preclinical, clinical, and commercial needs, if any; • our CMOs and suppliers may not be able to execute our manufacturing procedures appropriately; • our CMOs and suppliers have their own proprietary methods, which we may not have access to if we wish to, or are required to, switch CMOs or suppliers.
These risks include: • our CMOs and suppliers may be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical, and commercial needs, if any; • our CMOs and suppliers may not be able to execute our manufacturing procedures appropriately; • our CMOs and suppliers have their own proprietary methods, which we may not have access to if we wish to, or are required to, switch CMOs or suppliers.
Our ability to generate product revenue, which we do not expect will occur for many years, if ever, will be a result of the successful development and eventual commercialization of our product candidates, which may never occur. Our product candidates may have expected or unexpected adverse side effects or fail to demonstrate safety and efficacy.
Our ability to generate product revenue, which we do not expect will occur for many years, if ever, will be a result of the successful development and eventual commercialization of these product candidates, which may never occur. These product candidates may have expected or unexpected adverse side effects or fail to demonstrate safety and efficacy.
In any event, we will require additional capital for the further research, development, and commercialization of our product candidates, including potentially establishing our own internal manufacturing capabilities. Any additional fundraising efforts may divert our management from their day-to-day activities, which may adversely affect our ability to research, develop, and commercialize our product candidates.
In any event, we will require additional capital for the further development and commercialization of our product candidates, including potentially establishing our own internal manufacturing capabilities. Any additional fundraising efforts may divert our management from their day-to-day activities, which may adversely affect our ability to develop and commercialize our product candidates.
The implementation of cost containment measures that third-party payors and healthcare providers are instituting and any other healthcare reforms may prevent us from being able to generate, or may reduce, our revenues from the sale of our product candidates, if approved, and our product candidates may not be profitable.
The implementation of cost containment measures that third-party payors and healthcare providers are instituting and any other healthcare reforms may prevent us from being able to generate, or may reduce, our revenues from the sale of our product candidates, if approved, and our products may not be profitable.
The time and effort to qualify a new supplier or CMO, including to meet any regulatory requirements for such qualification, could result in additional costs, diversion of resources, or reduced manufacturing yields, any of which would negatively impact our operating results.
The time and effort to qualify a new supplier or CMO, including to meet any regulatory requirements for such qualification, could result in additional costs, diversion of resources, reduced manufacturing yields, or delays, any of which would negatively impact our operating results.
Additionally, invalidation trials or appeals thereof of the CVC IP are ongoing in China, India, and Japan. Such proceedings are often lengthy and can lead to the revocation of a patent in its entirety, the maintenance of the patent as granted, or, depending upon the jurisdiction, the maintenance of a patent in amended form.
Additionally, invalidation trials or appeals thereof of the CVC IP are ongoing in China and India. Such proceedings are often lengthy and can lead to the revocation of a patent in its entirety, the maintenance of the patent as granted, or, depending upon the jurisdiction, the maintenance of a patent in amended form.
The inability to recruit or retain certain executive officers, key employees, consultants, or advisors may impede the progress of our research, development, and commercialization objectives and have a material adverse effect on our business, intellectual property, financial condition, results of operations, and prospects.
The inability to recruit or retain certain executive officers, key employees, consultants, or advisors may impede the progress of our development and commercialization objectives and have a material adverse effect on our business, intellectual property, financial condition, results of operations, and prospects.
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.
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; • 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 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.
These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient enrollment for participation in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our development programs.
These competitors also compete with us in recruiting and retaining qualified clinical and management personnel and establishing clinical trial sites and patient enrollment for participation in clinical trials, as well as in acquiring technologies complementary to, or necessary for, our development programs.
We may form or seek collaborations or strategic alliances in the future for the development and commercialization of one or more of our product candidates or for new product candidates. We may not be successful in those efforts and, even if we do enter into any collaborations, they may not be successful.
We may form or seek new strategic collaborations in the future for the development and commercialization of one or more of our product candidates or for new product candidates. We may not be successful in those efforts and, even if we do enter into any collaborations, they may not be successful.
We expect to spend a substantial amount of capital in the research, development, and manufacture of our product candidates, particularly as we advance our CAR-T cell therapy product candidates through succeeding clinical phases with greater numbers of patients.
We expect to spend a substantial amount of capital in the clinical development and manufacture of our product candidates, particularly as we advance our CAR-T cell therapy product candidates through succeeding clinical phases with greater numbers of patients.
We may sell common stock, convertible securities, or other equity securities in one or more transactions at prices and in a manner we determine from time to time and investors may be substantially diluted by those issuances and sales.
We may sell common stock, convertible securities, or other equity securities in one or more transactions at prices and in a manner we determine from time to time and existing investors may be substantially diluted by those issuances and sales.
Such reforms could have an adverse effect on anticipated revenue from product candidates for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop product candidates.
Such reforms could have an adverse effect on anticipated revenue from products for which we may obtain regulatory approval and may affect our overall financial condition and ability to develop product candidates.
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.
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 Tax Code.
Events that may prevent successful or timely completion of clinical development include: • the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical trials; • delays or failure to obtain regulatory clearance to initiate our clinical trials, as well as delays or failures to obtain any necessary approvals by the clinical sites; • delays, suspension, or termination of our clinical trials by the clinical sites; • modification of clinical trial protocols; • delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites, as well as possible future breaches of such agreements; • failure to manufacture sufficient quantities of our product candidates for use in our clinical trials; • failure by CMOs, suppliers, CROs, or clinical trial sites to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all; • imposition of a temporary or permanent clinical hold by us, IRBs for the institutions at which such trials are being conducted, or by the FDA or other regulatory authorities for safety or other reasons, such as a result of a new safety finding in a clinical trial on a similar product by one of our competitors, that presents unreasonable risk to clinical trial participants; • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; • changes in the standard of care on which we developed our clinical development plan, which may require new or additional trials; • the cost of clinical trials of our product candidates being greater than we anticipated; • insufficient funding to continue clinical trials with our product candidates; • the emergence of unforeseen safety issues or undesirable side effects; • clinical trials of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development of our product candidates; • inability to establish clinical trial endpoints that applicable regulatory authorities consider clinically meaningful, or, if we seek accelerated approval, that applicable regulatory authorities consider likely to predict clinical benefit; • regulators withdrawing their approval of a product or imposing restrictions on its distribution; and • interruptions, delays, or staffing shortages resulting from pandemics or other public health crises.
Events that may prevent successful or timely completion of clinical development include: • the FDA or comparable foreign regulatory authorities disagreeing as to the design or implementation of our clinical trials; • delays or failure to obtain regulatory clearance to initiate our clinical trials, as well as delays or failures to obtain any necessary approvals by the clinical sites; • delays, suspension, or termination of our clinical trials by the clinical sites; • modification of clinical trial protocols; • delays in reaching agreement on acceptable terms with prospective CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites, as well as possible future breaches of such agreements; • failure to manufacture sufficient quantities of our product candidates for use in our clinical trials; 47 Table of Contents • failure by CMOs, suppliers, CROs, or clinical trial sites to comply with regulatory requirements and clinical trial protocols or to meet their contractual obligations to us in a timely manner, or at all; • imposition of a temporary or permanent partial or full clinical hold by us, IRBs for the institutions at which such trials are being conducted, or by the FDA or other regulatory authorities for safety or other reasons, such as a result of a new safety finding in a clinical trial on a similar product by one of our competitors, that presents unreasonable risk to clinical trial participants; • changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; • changes in the standard of care on which we developed our clinical development plan, which may require new or additional trials; • the cost of clinical trials of our product candidates being greater than we anticipated; • insufficient funding to continue clinical trials with our product candidates; • the emergence of unforeseen safety issues or undesirable side effects; • clinical trials of our product candidates producing negative or inconclusive results, which may result in our deciding, or regulators requiring us, to conduct additional clinical trials or abandon development of our product candidates; • inability to establish clinical trial endpoints that applicable regulatory authorities consider clinically meaningful, or, if we seek accelerated approval, that applicable regulatory authorities consider reasonably likely to predict clinical benefit; • regulators withdrawing their approval of a product or imposing restrictions on its distribution; and • interruptions, delays, or staffing shortages resulting from pandemics or other public health crises.
In addition, the design of a clinical trial can determine whether its results will support approval of our product candidates, and flaws in the design of a clinical trial may not be apparent until the clinical trial is well advanced.
The design of a clinical trial can determine whether its results will support approval of our product candidates, and flaws in the design of a clinical trial may not be apparent until the clinical trial is well advanced.
To become and remain profitable, we must develop and eventually commercialize product candidates with significant market potential, which will require us to be successful in a range of challenging activities.
To become and remain profitable, we must continue to develop and eventually commercialize product candidates with significant market potential, which will require us to be successful in a range of challenging activities.
Over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, and has had to furlough critical government employees and stop critical activities.
Over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical government employees and stop critical activities.
The information that we choose to disclose publicly regarding preclinical studies or clinical trials is typically a summary of extensive information, and others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities, or otherwise regarding a particular product candidate or our product candidates generally.
The information that we choose to disclose publicly regarding nonclinical studies or clinical trials is typically a summary of extensive information, and others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities, or otherwise regarding a particular product candidate or our product candidates generally.
The success of any future strategic transaction depends on various risks and uncertainties, including: • unanticipated liabilities related to acquired companies or joint ventures; • difficulties integrating acquired personnel, technologies, and operations into our existing business; • retention of key employees; • diversion of management’s time and focus from operating our business to management of strategic alliances or joint ventures or acquisition integration challenges; • increases in our expenses and reductions in our cash available for operations and other uses; • disruption in or termination of our relationships with collaborators or suppliers as a result of such a transaction; and • possible write-offs or impairment charges relating to acquired businesses or joint ventures.
The success of any future strategic transaction depends on various risks and uncertainties, including: • unanticipated liabilities related to acquired companies or joint ventures; • difficulties integrating acquired personnel, technologies, and operations into our existing business; • retention of key employees; • diversion of management’s time and focus from operating our business to management of new strategic collaborations or joint ventures or acquisition integration challenges; • increases in our expenses and reductions in our cash available for operations and other uses; • disruption in or termination of our relationships with collaborators or suppliers as a result of such a transaction; and • possible write-offs or impairment charges relating to acquired businesses or joint ventures.
Because our cell therapy product candidates are edited with CRISPR chRDNA guides, our products may be perceived to have additional or greater safety risks.
Additionally, because our cell therapy product candidates are edited with CRISPR chRDNA guides, our products may be perceived to have additional or greater safety risks.
Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is intended to treat a rare disease or condition, defined as a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States.
Under the Orphan Drug Act, the FDA may designate a drug or biologic as an orphan drug if it is intended to treat a rare disease or condition, defined as a patient population of fewer than 200,000 in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug or biologic will be recovered from sales in the United States.
Preclinical results in animals may not be predictive of safety or efficacy in humans. Failure can occur at any time during the preclinical study and clinical trial processes and because we have never successfully commercialized a product and our first product candidate is in an early stage of clinical development, there is a high risk of failure.
Nonclinical results in animals may not be predictive of safety or efficacy in humans. Failure can occur at any time during the nonclinical study and clinical trial processes and because we have never successfully commercialized a product and our first product candidate is in an early stage of clinical development, there is a high risk of failure.
In addition, as a smaller reporting company, we may choose to present only the two most recent fiscal years of audited financial statements in our Annual Report on Form 10-K. We cannot predict if investors will find our common stock less attractive if we rely on emerging growth company or smaller reporting company exemptions.
In addition, as a smaller reporting company, we may choose to present only the two most recent fiscal years of audited financial statements in our Annual Reports on Form 10-K. We cannot predict if investors will find our common stock less attractive if we rely on emerging growth company or smaller reporting company exemptions.
In addition, our current reliance on a limited number of CMOs and suppliers exposes us to a variety of risks, each of which could delay our preclinical studies, clinical trials, the approval, if any, of our product candidates by the FDA or foreign regulatory authorities, or the commercialization of our product candidates or result in higher costs or deprive us of potential product revenue.
In addition, our current reliance on a limited number of CMOs and suppliers exposes us to a variety of risks, each of which could delay our clinical trials, the approval, if any, of our product candidates by the FDA or foreign regulatory authorities, or the commercialization of our product candidates or result in higher costs or deprive us of potential product revenue.
As our product candidates proceed through preclinical studies to clinical trials to regulatory review, and potential marketing approval and commercialization, it is common that various aspects of our manufacturing methods will be altered along the way to optimize processes and results. Such changes carry the risk that intended objectives will not be achieved.
As our product candidates proceed through clinical trials to regulatory review, and potential marketing approval and commercialization, it is common that various aspects of our manufacturing methods will be altered along the way to optimize processes and results. Such changes carry the risk that intended objectives will not be achieved.
This landmark Loper decision may invite various stakeholders to bring lawsuits against the FDA to challenge longstanding decisions and policies of the FDA, including the FDA’s statutory interpretations of market exclusivities and the “substantial evidence” requirements for drug approvals, which could undermine the FDA’s authority, lead to uncertainty in the industry, and disrupt the FDA’s normal operations.
This landmark Loper decision may invite various stakeholders to bring lawsuits against the FDA to challenge longstanding decisions and policies of the FDA, including the FDA’s statutory interpretations of market exclusivities and the “substantial evidence” requirements for regulatory approvals, which could undermine the FDA’s authority, lead to uncertainty in the industry, and disrupt the FDA’s normal operations.
We have not previously submitted a BLA to the FDA or made a similar submission to any foreign regulatory authority. A BLA must include extensive preclinical and clinical data and supporting information to establish our product candidate’s safety and efficacy for each desired indication. The BLA must also include significant information regarding the chemistry, manufacturing, and controls for our product.
We have not previously submitted a BLA to the FDA or made a similar submission to any foreign regulatory authority. A BLA must include extensive nonclinical and clinical data and supporting information to establish our product candidate’s safety and efficacy for each desired indication. A BLA must also include significant information regarding the chemistry, manufacturing, and controls for our product.
Even if we are able to commercialize our product candidates, such products may be subject to unfavorable pricing regulations, third-party reimbursement practices, or healthcare reform initiatives, which could harm our business. The regulations that govern marketing approvals, pricing, and reimbursement for new biologic products vary widely from country to country.
Even if we are able to commercialize our product candidates, such products may be subject to unfavorable pricing regulations, third-party reimbursement practices, or healthcare reform initiatives, which could harm our business. The regulations that govern marketing approvals, pricing, and reimbursement for new biologics vary widely from country to country.
Our ability to generate product revenue or profits, which we do not expect to occur for many years, if ever, will depend heavily on the successful development and eventual commercialization of our product candidates, which may never occur. Unless we receive approval from the FDA or other regulatory authorities for our product candidates, we will not have product revenues.
Our ability to generate product revenue or profits, which we do not expect to occur for many years, if ever, will depend heavily on the successful development and eventual commercialization of our product candidates. Unless we receive approval from the FDA or other regulatory authorities for our product candidates, we will not have product revenues.
In addition, varying interpretations of the data obtained from preclinical studies and clinical trials could delay, limit, or prevent marketing approval of our product candidates. Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render our approved product not commercially viable.
In addition, varying interpretations of the data obtained from nonclinical studies and clinical trials could delay, limit, or prevent marketing approval of our product candidates. Any marketing approval we ultimately obtain may be limited or subject to restrictions or post-approval commitments that render our approved product not commercially viable.
Our success also depends on our ability to continue to attract, retain, and motivate entry-level, mid-level, and senior scientific personnel as well as managers. We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies, as well as academic and research institutions, for similar personnel.
Our success also depends on our ability to continue to attract, retain, and motivate entry-level, mid-level, and senior personnel. We may not be able to attract and retain these personnel on acceptable terms given the competition among numerous pharmaceutical and biotechnology companies, as well as academic and research institutions, for similar personnel.
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.
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 nonclinical studies or clinical trials. The same may happen with review of our product candidates by foreign regulatory authorities.
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.
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.
As of December 31, 2024, substantially all our cash on deposit was maintained at four financial institutions in the United States, and our current deposits are in excess of federally insured limits. If further failures in financial institutions where we hold deposits occur, we could experience additional risk.
As of December 31, 2025, substantially all our cash on deposit was maintained at four financial institutions in the United States, and our current deposits are in excess of federally insured limits. If further failures in financial institutions where we hold deposits occur, we could experience additional risk.
The clinical trial requirements of the FDA and other regulatory authorities, and the criteria these regulators use to determine the safety and efficacy of a product candidate, vary substantially according to the type, complexity, novelty, intended use, and target population of our product candidates. The outcome of preclinical studies and clinical trials is inherently uncertain.
The clinical trial requirements of the FDA and other regulatory authorities, and the criteria these regulators use to determine the safety and efficacy of a product candidate, vary substantially according to the type, complexity, novelty, intended use, and target population of our product candidates. The outcome of nonclinical studies and clinical trials is inherently uncertain.
From January 1, 2021, companies have had to comply with the GDPR and also the United Kingdom GDPR (“UK GDPR”), which, together with the amended United Kingdom Data Protection Act 2018, retains the GDPR in UK national law. The relationship between the United Kingdom and the EU in relation to certain aspects of data protection law remains unclear.
From January 1, 2021, companies have had to comply with the GDPR and also the UK GDPR (“UK GDPR”), which, together with the amended UK Data Protection Act 2018, retains the GDPR in UK national law. The relationship between the UK and the EU in relation to certain aspects of data protection law remains unclear.
Any of the above could significantly harm our business, financial condition, results of operations, and prospects and cause the price of our common stock to decline. Raising additional capital may cause dilution to our stockholders, restrict our operations, and/or require us to relinquish rights to our technologies or product candidates.
Any of the above could significantly harm our business, financial condition, results of operations, and prospects and cause the price of our common stock to decline. Raising additional capital may cause dilution to our stockholders, restrict our operations, and/or require us to relinquish rights to our genome-editing technologies or product candidates.
Any product candidates we may develop, and the activities associated with their development and commercialization, including their manufacture, preclinical and clinical development, safety, efficacy, recordkeeping, labeling, storage, advertising, promotion, sale, and distribution, are subject to comprehensive regulation by the FDA and other regulatory authorities.
Any product candidates we may develop, and the activities associated with their development and commercialization, including their manufacture, nonclinical and clinical development, safety, efficacy, recordkeeping, labeling, storage, advertising, promotion, sale, and distribution, are subject to comprehensive regulation by the FDA and other regulatory authorities.
We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with these laws and regulations. In addition, we may incur substantial costs to comply with current or future environmental, health, and safety laws and regulations. These current or future laws and regulations may impair our product candidate development and research program efforts.
We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with these laws and regulations. In addition, we may incur substantial costs to comply with current or future environmental, health, and safety laws and regulations. These current or future laws and regulations may impair our product candidate development efforts.
As a result, our effective tax rate is derived from a combination of applicable tax rates in the locations in which we operate. In preparing our financial statements, we estimate the amount of tax that will become payable in each jurisdiction using enacted tax rates as of the balance sheet date.
As a result, our effective tax rate is derived from a combination of applicable tax rates in the locations in which we operate. In preparing our financial statements, we estimate the amount of tax, if any, that will become payable in each jurisdiction using enacted tax rates as of the balance sheet date.
Some of the factors that may cause the market price of our common stock to fluctuate include: • the timing and results of preclinical studies and clinical trials for any product candidates that we develop; • delay, failure, or discontinuation of any of our product candidates or research programs; • results of preclinical studies, clinical trials, or regulatory approvals of product candidates of our competitors, or announcements about new research programs or product candidates of our competitors; • adverse regulatory decisions, including failure to receive regulatory approval of one or more of our product candidates; • unanticipated or serious safety concerns related to our product candidates; • developments or changing views regarding the use of biologics, including those that involve genome editing; • commencement or termination of collaborations; • regulatory or legal developments in the United States and other countries; • assertions that our product candidates infringe third-party patents; • invalidity challenges to our intellectual property, including intellectual property that we have in-licensed; • manufacturing delays and delays caused by supply chain issues; • acceptance or lack of acceptance of allogeneic CAR-T cell therapies as compared with autologous CAR-T cell therapies and perceptions that allogeneic CAR-T cell therapies do not maintain a durable response; • inability to obtain collaboration partners; • the recruitment and retention of key personnel; • the level of expenses related to any of our product candidates, including preclinical studies and clinical trials, as well as the level related to our research programs; • the results of our efforts to develop additional product candidates or technologies; • actual or anticipated changes in estimates as to financial results, development timelines, or recommendations by securities analysts; • announcements or expectations of additional financing efforts; • significant lawsuits, including contract disputes with our licensors, licensees, assignors, assignees, suppliers, CMOs, CROs, clinical sites, or securities class action litigation; • sales of our common stock by us, our insiders, or other stockholders; • variations in our financial results or those of companies that are perceived to be similar to us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; 89 Tabl e of Contents • general economic and political conditions such as recessions, inflationary pressures, interest rates, fuel prices, elections, drug pricing policies, international currency fluctuations, acts of war or terrorism, geopolitical events, and public health crises; and • the other factors described in this “Risk Factors” section.
Some of the factors that may cause the market price of our common stock to fluctuate include: • the timing and results of our clinical trials; • delay, failure, or discontinuation of any of our product candidates; • results of nonclinical studies, clinical trials, or regulatory approvals of product candidates of our competitors, or announcements about new research programs or product candidates of our competitors; • adverse regulatory decisions, including failure to receive regulatory approval of one or more of our product candidates; • unanticipated or serious safety concerns related to our product candidates; • developments or changing views regarding the use of biologics, including those that involve genome editing; • commencement or termination of collaborations; • regulatory or legal developments in the United States and other countries; • assertions that our product candidates infringe third-party patents; • invalidity challenges to our intellectual property, including intellectual property that we have in-licensed; • manufacturing delays and delays caused by supply chain issues; 93 Table of Contents • acceptance or lack of acceptance of allogeneic CAR-T cell therapies as compared with autologous CAR-T cell therapies and perceptions that allogeneic CAR-T cell therapies do not maintain a durable response; • inability to obtain and maintain collaboration partners; • the recruitment and retention of key personnel; • the level of expenses related to any of our product candidates, including clinical trials; • the results of our efforts to develop additional product candidates or technologies; • actual or anticipated changes in estimates as to financial results, development timelines, or recommendations by securities analysts; • announcements, expectations, or structures of additional financing efforts; • significant lawsuits, including contract disputes with our licensors, licensees, assignors, assignees, suppliers, CMOs, CROs, clinical sites, or securities class action litigation; • sales of our common stock by us, our insiders, or other stockholders; • variations in our financial results or those of companies that are perceived to be similar to us; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic and political conditions such as recessions, inflationary pressures, interest rates, fuel prices, elections, drug and biologic pricing policies, international currency fluctuations, acts of war or terrorism, geopolitical events, and public health crises; and • the other factors described in this “Risk Factors” section.
For any violations of laws and regulations during the conduct of our preclinical studies and clinical trials, we could be subject to warning letters or enforcement action that may include civil and other penalties, up to and including criminal prosecution.
For any violations of laws and regulations during the conduct of our clinical trials, we could be subject to warning letters or enforcement action that may include civil and other penalties, up to and including criminal prosecution.
We have devoted almost all of our financial resources to research and development, including our preclinical development activities.
We have devoted almost all of our financial resources to research and development, including our preclinical and clinical development activities.
Before obtaining regulatory approval for the commercial sale of any of our product candidates, we must demonstrate through lengthy, complex, and expensive preclinical studies and clinical trials that our product candidates are both safe and effective for their intended use.
Before obtaining regulatory approval for the commercial sale of any of our product candidates, we must demonstrate through lengthy, complex, and expensive nonclinical studies and clinical trials that our product candidates are both safe and effective for their intended use.
Any of these occurrences may harm our business, financial condition, results of operations, and prospects. The FDA or other regulatory agencies may disagree with our regulatory plans and we may fail to obtain regulatory approval of our cell therapy product candidates.
Any of these occurrences may harm our business, financial condition, results of operations, and prospects. The FDA or other regulatory agencies may disagree with our regulatory plans and we may fail to obtain regulatory approval of our CAR-T cell therapy product candidates.
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.
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.
As a result of these factors, it is difficult for us to predict the time and cost of our product candidate development, and we cannot predict whether the application of our chRDNA technologies, or other genome-editing technologies we may use in the future, will result in the identification, development, preclinical studies, and clinical trials to support regulatory approval of any of our cell therapy product candidates.
As a result of these factors, it is difficult for us to predict the time and cost of our product candidate development, and we cannot predict whether the application of our chRDNA technology, or other genome-editing technologies we may use in the future, will result in the identification, development, nonclinical studies, and clinical trials to support regulatory approval of any future cell therapy product candidates.
Since the regulatory framework in the United Kingdom covering pharmaceutical products is derived from EU directives and regulations, Brexit could materially impact the future regulatory requirements for product candidates and products in the United Kingdom as there is now potential for the UK regulations to diverge from the EU regulations.
Since the regulatory framework in the UK covering pharmaceutical products is derived from EU directives and regulations, Brexit could materially impact the future regulatory requirements for product candidates and products in the UK as there is now potential for the UK regulations to diverge from the EU regulations.
Since the COVID pandemic, many of our non-researchers work remotely or on a hybrid work schedule. This may lead to employees not feeling as connected to our company and thus more inclined to pursue other opportunities.
Since the COVID pandemic, many of our employees work remotely or on a hybrid work schedule. This may lead to employees not feeling as connected to our company and thus more inclined to pursue other opportunities.
Any failure to report our financial results on an accurate and timely basis could result in sanctions, lawsuits, delisting of our shares from Nasdaq, or other adverse consequences that would materially and adversely affect our business, financial condition, results of operations, and prospects. We do not expect to pay any dividends for the foreseeable future.
Any failure to report our financial results on an accurate and timely basis could result in sanctions, lawsuits, delisting of our shares from Nasdaq, or other adverse consequences that would materially and adversely affect our business, financial condition, results of operations, and prospects. 97 Table of Contents We do not expect to pay any dividends for the foreseeable future.
We are subject to securities class action litigation, and our officers and directors may be subject to shareholder derivative lawsuits, which may result in substantial costs and a diversion of management's attention and resources, which could harm our business.
We may be subject to securities class action litigation, and our officers and directors may be subject to shareholder derivative lawsuits, which will result in substantial costs and a diversion of management's attention and resources, which could harm our business.
As a result, the information we provide stockholders will be different than the information that is available with respect to some other public companies. In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards.
As a result, the information we provide stockholders will be different than the information that is available with respect to some other public companies. 96 Table of Contents In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards.
In addition, the longer term economic, legal, political, regulatory, and social framework to be put in place between the United Kingdom and the EU has had, and may continue to have, a material and adverse effect on global economic conditions and the stability of global financial markets and may significantly reduce global market liquidity and restrict the ability of key market participants to operate in certain financial markets.
In addition, the longer term economic, legal, political, regulatory, and social framework to be put in place between the UK and the EU has had, and may continue to have, a material and adverse effect on global economic conditions and the stability of global financial markets and may significantly reduce global market liquidity and restrict the ability of key market participants to operate in certain financial markets.
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.
All these factors could be costly to us and otherwise harm our business, financial condition, results of operations, and prospects. 44 Table of Contents 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.
However, some uncertainty over interpretation of the law remains, and there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider our product candidates to be reference products for competing products, potentially creating the opportunity for biosimilar competition sooner than anticipated.
However, some uncertainty over interpretation of the law remains, and there is a risk that this exclusivity could be shortened due to congressional action or otherwise, or that the FDA will not consider our product candidates eligible for reference product exclusivity, potentially creating the opportunity for biosimilar competition sooner than anticipated.
We also rely on know-how and continuing technological innovation to develop and maintain our competitive position. If we are unable to obtain or maintain intellectual property protection with respect to our CRISPR chRDNA genome-editing platform technologies and product candidates, our business, financial condition, results of operations, and prospects will be materially harmed.
We also rely on know-how and continuing technological innovation to develop and maintain our competitive position. If we are unable to obtain or maintain intellectual property protection with respect to our CRISPR chRDNA genome-editing technology and product candidates, our business, financial condition, results of operations, and prospects will be materially harmed.
If the FDA or foreign regulatory authorities require us to complete additional preclinical studies or we are required to satisfy other requests for additional data or information, our clinical trials may be delayed.
If the FDA or foreign regulatory authorities require us to complete additional nonclinical studies or we are required to satisfy other requests for additional data or information, our clinical trials may be delayed.
Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations, and prospects. If our trademarks are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
Should any of these events occur, they could have a material adverse effect on our business, financial condition, results of operations, and prospects. 77 Table of Contents If our trademarks are not adequately protected, then we may not be able to build name recognition in our markets of interest and our business may be adversely affected.
Many of the biotechnology companies and research institutions that we compete against for qualified personnel and consultants have greater financial and other resources, different risk profiles, and a longer history in the industry than we do. Recruiting and retaining qualified research, development, manufacturing, regulatory, and clinical personnel is critical to our success.
Many of the biotechnology companies and research institutions that we compete against for qualified personnel and consultants have greater financial and other resources, different risk profiles, and a longer history in the industry than we do. 84 Table of Contents Recruiting and retaining qualified development, manufacturing, regulatory, and clinical personnel is critical to our success.
A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising results in earlier trials. Based upon negative or inconclusive results, we may decide, or regulatory agencies may require us, to conduct additional clinical trials or preclinical studies.
A number of companies in the biopharmaceutical industry have suffered significant setbacks in advanced clinical trials due to lack of sufficient efficacy or adverse safety profiles, notwithstanding promising results in earlier trials. Based upon negative or inconclusive results, we may decide, or regulatory agencies may require us, to conduct additional clinical trials or nonclinical studies.
For example, on March 10, 2023, Silicon Valley Bank (“SVB”) was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation (“FDIC”) as receiver. Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp. were each put into receivership. Although the U.S.
For example, on March 10, 2023, Silicon Valley Bank (“SVB”) was closed by the California Department of Financial Protection and Innovation, which appointed the Federal Deposit Insurance Corporation (“FDIC”) as receiver. Similarly, on March 12, 2023, Signature Bank and Silvergate Capital Corp. were each put into receivership.
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.
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; 88 Table of Contents • 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; • 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.
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.
Our product candidates are in various stages of clinical development. 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.
For example, if a collaborator were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under such collaboration could be delayed, diminished, or terminated; and • collaboration agreements may be terminated and, if terminated, we may find it more difficult to find a suitable replacement collaborator or attract new collaborators, resulting in a need for additional capital to pursue further development or commercialization of the applicable product candidates we may develop.
For example, if a collaborator were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under such collaboration could be delayed, diminished, or terminated; and 83 Table of Contents • collaboration agreements may be terminated and, if terminated, it may be more difficult for us to find a suitable replacement collaborator or attract new collaborators, resulting in a need for additional capital to pursue further development or commercialization of the applicable product candidates we may develop.
Any of these actions could have a material adverse effect on our business, financial condition, results of operations, and prospects. We have a limited operating history, which may make it difficult to evaluate our technologies and product candidate development capabilities or to predict our future performance.
Any of these actions could have a material adverse effect on our business, financial condition, results of operations, and prospects. 40 Table of Contents We have a limited operating history, which may make it difficult to evaluate our technologies and product candidate development capabilities or to predict our future performance.
Even if we comply with all FDA requests, we may still fail to obtain regulatory approval. We cannot be sure that we will ever obtain regulatory clearance for our product candidates.
Even if we comply with all FDA requests and requirements, we may still fail to obtain regulatory approval. We cannot be sure that we will ever obtain regulatory clearance for our product candidates.
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.
Since 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.
If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay, or discontinue one or more of our product candidate preclinical studies, clinical trials, or development and commercialization, or we may be unable to expand our operations or otherwise capitalize on our business opportunities, as desired.
If we are unable to obtain funding on a timely basis, we may be required to significantly delay initiation, curtail, or discontinue one or more of our product candidate clinical trials, or development and commercialization, or we may be unable to expand our operations or otherwise capitalize on our business opportunities, as desired.
Although the FDA has found substantial evidence to support approval outside of the traditional phase 1, phase 2, and phase 3 framework for the approved autologous anti-CD19 and anti-BCMA CAR-T cell therapies, the general approach for FDA approval of a new biologic is for the sponsor to provide dispositive data from at least two adequate and well-controlled clinical trials of the relevant biologic in the applicable patient population.
Although the FDA has found substantial evidence of effectiveness to support approval outside of the traditional phase 1, phase 2, and phase 3 framework for the approved autologous anti-CD19 and anti-BCMA CAR-T cell therapies, the general approach for FDA approval of a new biologic is for the sponsor to provide dispositive data from adequate and well-controlled clinical trials of the relevant biologic in the applicable patient population.
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.
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.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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For 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.
For 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, 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.
Our day-to-day cybersecurity risk management and strategy processes are overseen by representatives from our IT, finance, and legal departments. Such individuals have an average of over 15 years of prior work experience in various roles involving IT security, auditing, compliance, data protection, privacy, risk management, systems, and programming.
Our day-to-day cybersecurity risk management and strategy processes are overseen by representatives from our IT, finance, and legal departments. Such individuals have an average of over 20 years of prior work experience in various roles involving IT security, auditing, compliance, data protection, privacy, risk management, systems, and programming.
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
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.
We also leverage third-party expertise to audit and test our cybersecurity program. These include periodic reviews of cybersecurity threats and related controls, including reviews of periodic penetration tests conducted by independent third parties. We have implemented processes to manage the cybersecurity risks associated with our use of third-party service providers.
These include periodic reviews of cybersecurity threats and related controls, including reviews of periodic penetration tests conducted by independent third parties. We have implemented processes to manage the cybersecurity risks associated with our use of third-party service providers.
To defend, detect, and respond to cybersecurity incidents, we perform cybersecurity reviews of systems and applications; audits of applicable data policies; regular vulnerability assessments and penetration testing using external third-party tools to test security control; security incident and event management; continuous monitoring, and threat intelligence gathering; conduct employee training; and implement appropriate changes.
To defend, detect, and respond to cybersecurity incidents, we perform cybersecurity reviews of systems and applications; audits of applicable data policies; regular vulnerability assessments and penetration testing using external third-party tools to test security control; security incident and event management; continuous monitoring, and threat intelligence gathering; conduct employee training; and implement appropriate changes. 99 Table of Contents We also leverage third-party expertise to audit and test our cybersecurity program.
This includes proactive monitoring of third party’s configurations, risk questionnaires for new technology vendors, and other processes to minimize risks associated with our third-party providers. Security events and data incidents are evaluated, ranked by severity, and prioritized for response and remediation. Incidents are evaluated to determine materiality as well as operational and business impact, and reviewed for privacy impact.
This includes proactive monitoring of third-party service providers’ security protocols, risk questionnaires for new technology vendors, and other processes to minimize risks associated with our third-party providers. Security events and data incidents are evaluated, ranked by severity, and prioritized for response and remediation.
Our risk management program also assesses third-party risks, and we perform third-party risk management to identify and mitigate risks from third parties such as vendors and suppliers. Cybersecurity risks are evaluated when determining the selection and oversight of applicable third-party service providers and potential fourth-party risks when handling and/or processing our confidential information and data.
Cybersecurity risks are evaluated when determining the selection and oversight of applicable third-party service providers and potential fourth-party risks when handling and/or processing our confidential information and data. In addition to new vendor onboarding, we perform risk management during third-party cybersecurity compromise incidents to identify and mitigate risks to us from third parties.
Removed
In addition to new vendor onboarding, we perform risk management during third-party cybersecurity compromise incidents to identify and mitigate risks to us from third parties.
Added
Incidents are evaluated to determine materiality as well as operational and business impact, and reviewed for privacy impact. Our risk management program also assesses third-party risks, and we perform third-party risk management to identify and mitigate risks from third parties such as vendors and suppliers.

Item 2. Properties

Properties — owned and leased real estate

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See Note 8 to the consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information. We believe that our existing facilities are adequate for our near-term needs and that suitable additional facilities will be available in the future if and when needed.
See Note 8 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information. We believe that our existing facilities are adequate for our near-term needs and that suitable additional facilities will be available in the future if and when needed.
Item 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 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 July 2032 and March 2033. 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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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.
Haurwitz, et al, case number 4:25-cv-02199 (“First 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 from our company as well as that we make certain changes to our corporate governance.
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.
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.
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.
The Saylor Case complaint challenged disclosures regarding our business, operations, and prospects, specifically with respect to the alleged safety, efficacy, and durability of vispa-cel, the clinical results and commercial prospects for vispa-cel, and our financial statements, in alleged violation of Sections 10(b) and 20(a) of the Securities Exchange Act of 1934, as amended (“Exchange Act”).
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.
District Court for the Northern District of California against our company and certain of our current and former officers, Saylor v. Caribou Biosciences, Inc., et al., case number 3:24-cv-09413 (“Saylor Case”). The alleged class period was July 14, 2023, to July 16, 2024.
Item 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.
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. 100 Table of Contents On December 24, 2024, a putative class action lawsuit was filed in the U.S.
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”).
On March 11, 2025, a second shareholder derivative complaint was filed in the U.S. District Court for the Northern District of California against the same defendants as in the First Derivative Case, Allen, derivatively on behalf of Caribou Biosciences, Inc. v. Braunstein, et al. , case number 4:25-cv-02463 (“Second Derivative Case”), with the same allegations.
Removed
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.
Added
Item 3. Legal Proceedings. From time to time, we may become involved in litigation arising in the ordinary course of business.
Removed
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.
Added
On April 15, 2025, the lead plaintiff filed a motion to voluntarily dismiss the lawsuit and, on April 27, 2025, the court granted the motion, dismissing the lawsuit without prejudice. On March 3, 2025, a shareholder derivative complaint was filed in the U.S.
Removed
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.
Added
On April 1, 2025, the First Derivative Case and the Second Derivative Case were deemed related and assigned to the same judge and, on April 7, 2025, the First Derivative Case and the Second Derivative Case were consolidated into a single action, In re Caribou Biosciences, Inc. Derivative Litigation , lead case number 4:25-cv-02199 (“Consolidated Derivative Action”).
Removed
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.
Added
The plaintiffs in the Consolidated Derivative Action filed an amended complaint on July 7, 2025. The amended complaint largely tracked the claims from the original complaints, but it also challenged additional disclosures as false or misleading. On August 21, 2025, the defendants filed a motion to dismiss the complaint.
Removed
The Derivative Case is at the preliminary stage of the proceedings. Item 4. Mine Safety Disclosures. Not applicable.
Added
On October 16, 2025, the parties filed a stipulation to voluntarily dismiss the lawsuit without prejudice, which the court granted on October 17, 2025. Item 4. Mine Safety Disclosures. Not applicable. 101 Table of Contents PART II

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Recent 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.
Recent 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] 102 Table of Contents
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.
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 February 27, 2026, we had 34 holders of record of our common stock.

Item 7. Management's Discussion & Analysis

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

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We have no current ongoing material financing commitments, such as lines of credit or guarantees, that are expected to affect our liquidity over the next five years, except for our lease commitments, and payments under certain of our license agreements as described in Note 4 and Note 9, respectively, to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
We have no current ongoing material financing commitments, such as lines of credit or guarantees, that are expected to affect our liquidity over the next five years, except for our lease commitments and payments under certain of our license agreements as described in Notes 4 and Note 9, respectively, to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K.
Personnel-related costs consist of salaries, benefits, and stock-based compensation for our general and administrative personnel. Intellectual property costs include expenses for filing, prosecuting, and maintaining patents and patent applications, including certain patents and patent applications that we license from third parties.
Personnel-related costs consist of salaries, benefits, and stock-based compensation expense for our general and administrative personnel. Intellectual property costs include expenses for filing, prosecuting, and maintaining patents and patent applications, including certain patents and patent applications that we license from third parties.
The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the consolidated financial statements, as well as the reported expenses incurred during the reporting periods.
The preparation of these consolidated financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of our consolidated financial statements, as well as the reported expenses incurred during the reporting periods.
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.
We expect to continue to rely on our CMOs for manufacturing our 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.
Some of these agreements include contingent payments that will become payable if and when we achieve certain development, regulatory, clinical, and/or commercial milestones. As of December 31, 2024, the satisfaction and timing of such contingent payments is uncertain and is not reasonably estimable.
Some of these agreements include contingent payments that will become payable if and when we achieve certain development, regulatory, clinical, and/or commercial milestones. As of December 31, 2025, the satisfaction and timing of such contingent payments is uncertain and is not reasonably estimable.
The capitalized amounts are recognized as expenses as the goods are delivered or as related services are performed. We separately track certain external costs on a program-by-program basis; however, we do not track costs that are deployed across multiple programs.
The capitalized amounts are recognized as expenses as the goods are delivered or as related services are performed. We separately track certain external costs on a program-by-program basis; however, we do not track costs that are deployed across our programs.
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.
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 (“scFv”) 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 expiring on June 29, 2026.
On June 29, 2023, in connection with the Pfizer Investment, we and Pfizer also entered into an Information Rights Agreement, having a 36-month term.
On June 29, 2023, in connection with the Pfizer Investment, we and Pfizer also entered into an Information Rights Agreement, having a 36-month term and expiring on June 29, 2026.
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.
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.
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.
We do not allocate internal costs as several of our departments support our programs and our payroll and other personnel expenses are not tracked on a program-by-program basis. Clinical development activities are central to our business model.
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.
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, 2025, and 2024 were $148.1 million and $149.1 million, respectively.
We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. Certain of our license agreements have two performance obligations: a license and a material right for annual license renewals.
We evaluate the measure of progress each reporting period and, if necessary, adjust the measure of performance and related revenue recognition. 113 Table of Contents Certain of our license agreements have two performance obligations: a license and a material right for annual license renewals.
If we raise additional funds through collaborations, strategic alliances, or licensing arrangements with third parties, we may have to relinquish valuable rights to our intellectual property, future revenue streams, research programs, or product candidates or grant licenses on terms that may not be favorable to us.
If we raise additional funds through new strategic collaborations or licensing arrangements with third parties, we may have to relinquish valuable rights to our intellectual property, future revenue streams, or product candidates or grant licenses on terms that may not be favorable to us.
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.
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.
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.
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 clinical development and manufacturing of our product candidates, including under agreements with CMOs, suppliers, contract research organizations (“CROs”), and clinical sites; and • other research and development costs, including lab supplies, and consulting services.
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.
Liquidity, Capital Resources, and Capital Requirements Sources of Liquidity Since our inception through December 31, 2025, we have raised an aggregate net proceeds of $849.0 million to fund our operations through our initial public offering (“IPO”); sales of convertible preferred stock; a 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 successful development of our CAR-T product candidates, as well as other potential future product candidates, is highly uncertain. Accordingly, at this time, we cannot reasonably estimate or know the nature, timing, and costs of the efforts that will be necessary to complete the development of our product candidates.
The successful development of our CAR-T product candidates is highly uncertain. Accordingly, at this time, we cannot reasonably estimate or know the nature, timing, and costs of the efforts that will be necessary to complete the development of our product candidates.
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 had an accumulated deficit of $596.5 million as of December 31, 2025. 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.
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.
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, new collaborations, structured or other non-dilutive financings, licensing arrangements, and/or other sources.
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 expenses, which primarily consist of expenditures related to clinical trials. 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 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.
Our genome-editing platform is based on our novel chRDNA ( C RISPR h ybrid R NA- DNA , or “chRDNA,” pronounced “chardonnay”) genome-editing technology, which enables more precise genome editing of allogeneic cell therapies.
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.
During each of the years ended December 31, 2025, and 2024, we recorded $1.2 million of patent cost reimbursements as a reduction to general and administrative expenses.
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.
Our future funding requirements will depend on many factors, including the following: • the initiation, progress, timing, costs, and results of clinical trials for our product candidates; • the clinical development plans we establish for these product candidates; • the outcome, timing, and cost of meeting regulatory requirements established by the FDA and other comparable foreign regulatory authorities; • potential impact of reductions in government spending and personnel; • 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 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; • the amount of revenue, if any, received from commercial sales of our product candidates, should any of our product candidates receive marketing approval; 110 Table of Contents • 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 and tariffs on the cost of our operations; and • the costs of operating as a public company, including defending against any future class action securities litigation and shareholder derivative lawsuits.
Furthermore, our operating plans may change, and we expect to need additional funds to meet operational needs and capital requirements for clinical trials and other research and development expenditures.
Furthermore, our operating plans may change, and we expect to need additional funds to meet operational needs and capital requirements for our clinical trials and development of our product candidates.
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).
Under the ATM Sales Agreement and the 2022 Shelf Registration Statement, we issued and sold an aggregate of 3,588,696 shares of our common stock at an average price per share of $4.71 for aggregate gross proceeds of $16.9 million ($16.2 million net of offering expenses).
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.
We anticipate that our expenses will increase substantially as we: • progress our clinical trials for our vispa-cel and CB-011 cell therapy product candidates, particularly as we advance vispa-cel in our planned pivotal clinical trial; • hire additional personnel, as needed; • acquire or in-license intellectual property, new technologies, and/or additional product candidates; • expand, maintain, enforce, and defend our intellectual property portfolio; 103 Table of Contents • seek regulatory and marketing approvals for our vispa-cel and CB-011 product candidates if our clinical trials are successful; • expand manufacturing capabilities and supply chain capacity for our vispa-cel and CB-011 product candidates; • experience any delays, challenges, or other issues associated with any of the above, including the failure of clinical trials meeting endpoints, generation of clinical trial data subject to differing interpretations, or the occurrence of potential safety issues or other development or regulatory challenges; • make royalty, milestone, or other payments under current, and any future, in-license or assignment agreements 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 future class action securities litigation.
There are no assurances that we will be successful in obtaining an adequate level of financing to support our business plans as needed on acceptable terms, or at all.
We cannot provide any assurance that we will be successful in obtaining an adequate level of financing to support our business plans as needed on acceptable terms, or at all.
The disruption and volatility in the global and domestic capital markets resulting from heightened inflation, capital market volatility, interest rate and currency rate fluctuations, artificial intelligence, government agency changes under the new Administration, any potential economic slowdown or recession, including trade wars or civil or political unrest (such as the ongoing war between Ukraine and Russia, conflict in the Middle East, and tension between China and Taiwan) may increase the cost of capital and limit our ability to access capital.
Disruptions and volatility in the global and domestic capital markets resulting from heightened inflation, tariffs, capital market volatility, interest rate and currency rate fluctuations, artificial intelligence (“AI”), political and geopolitical tensions, government agency changes, any potential economic slowdown or recession, including trade wars or civil or political unrest (such as the ongoing war between Ukraine and Russia, conflicts in the Middle East, including the recent hostilities involving Iran, tension between China and Taiwan, geopolitical tensions in Europe, South America, and elsewhere) may increase the cost of capital and limit our ability to access capital.
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 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, CD19 and B cell maturation antigen (“BCMA”).
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.
Under these agreements, we license rights to certain intellectual property controlled by us. 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.
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.
We are advancing two clinical-stage allogeneic CAR-T cell therapy product candidates for the treatment of patients with hematologic malignancies: • Vispacabtagene regedleucel (“vispa-cel,” formerly CB-010): an allogeneic anti-CD19 CAR-T cell therapy that has been evaluated in patients with relapsed or refractory B cell non-Hodgkin lymphoma (“r/r B-NHL”) in our ANTLER phase 1 clinical trial • CB-011: an allogeneic anti-BCMA CAR-T cell therapy that is being evaluated in patients with relapsed or refractory multiple myeloma (“r/r MM”) in our CaMMouflage 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.
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).
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, in accordance with the ATM Sales Agreement and the 2022 Shelf Registration Statement for aggregate gross proceeds of $15.7 million ($15.2 million net of offering expenses).
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.
General and Administrative Expenses General and administrative expenses decreased by $8.5 million to $37.9 million for the year ended December 31, 2025, from $46.5 million for the year ended December 31, 2024.
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. We cannot estimate when such payments will be due and none of these events is probable as of December 31, 2025.
Because of the numerous risks and uncertainties associated with the development of human therapeutics, we may never achieve profitability and, unless and until we are able to develop and commercialize our product candidates, we will need to continue to raise additional capital; however, funding may not be available to us on acceptable terms, or at all.
Because of the numerous risks and uncertainties associated with therapeutic product development, we may never achieve profitability and, unless and until we are able to develop and commercialize our product candidates, we will need to continue to raise additional capital.
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 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; conduct translational research to support our product candidates; seek regulatory approvals for our product candidates that successfully complete clinical trials; and hire additional personnel to support our clinical development efforts.
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).
Pursuant to the 2025 Shelf Registration Statement, we may, from time to time, sell up to $300.0 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 under the 2025 Shelf Registration Statement for our at-the-market equity offering program described below).
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.
If we raise additional funds through collaborations, new strategic collaborations, structured or other non-dilutive financings, or licensing arrangements with third parties, we may have to relinquish valuable rights to our intellectual property, future revenue streams, or product candidates or grant licenses on terms that may not be favorable to us.
We will continue to be dependent upon equity financing, debt financing, collaboration and licensing arrangements, and/or other forms of capital raises at least until we are able to generate significant positive cash flows from our operations.
We will continue to be dependent on equity financing, debt financing, collaboration and licensing arrangements, and/or other forms of capital raises, including structured or other non-dilutive financings, to fund operating expenses, including to fully fund our planned pivotal trial for vispa-cel, at least until we are able to generate significant positive cash flows from our operations.
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.
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 genome-editing platform technologies, and our in-licensing, assignment, and other third-party agreements.
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.
Leases We have two operating lease agreements for our laboratory and office space. As of December 31, 2025, we had lease payment obligations totaling $43.8 million, of which $4.8 million is due within 12 months. 111 Table of Contents Strategic Investment On June 29, 2023, we entered into a Securities Purchase Agreement (“Securities Purchase Agreement”) with Pfizer, Inc.
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.
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.
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”).
At-the-Market Equity Offering Program On August 9, 2022, we entered into an at-the-market Open Market Sale Agreement SM (“ATM Sales Agreement”) with Jefferies LLC (“Jefferies”), pursuant to which, on the terms and subject to the conditions and limitations set forth in the ATM Sales Agreement, from time to time, we could have issued and sold, through Jefferies, acting as sales agent, up to $100.0 million of our shares of common stock under the 2022 Shelf Registration Statement.
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 use our chRDNA technology to armor our cell therapy product candidates through genome-editing strategies, such as checkpoint disruption and immune cloaking, to enhance allogeneic CAR-T cell therapy activity against hematologic malignancies.
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.
Benefit From Income Taxes An income tax benefit of $0.6 million was recognized for the year ended December 31, 2025, which was primarily related to deferred federal and state taxes. An income tax benefit of less than $0.1 million was recognized for the year ended December 31, 2024, which was primarily rela ted to deferred state taxes.
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.
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.
The 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.
The duration, costs, and timing of 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; • establishment, maintenance, enforcement, and defense of our patents and other intellectual property rights; 105 Table of Contents • our ability to not infringe, misappropriate, or otherwise violate third-party intellectual property rights; • 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; • successful development of our internal process development and transfer to CMOs; • establishment and maintenance 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 nonpatent regulatory exclusivity for our product candidates; • establishment of sales, marketing, and distribution capabilities necessary for commercialization of our product candidates if 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 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.
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.
We make significant judgments and estimates in determining the accrual balance in each reporting period. As actual costs become known, we adjust our accruals.
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.
This decrease was primarily due to (i) a decrease of $8.8 million in other research and development expenses primarily related to the reduction in workforce and strategic pipeline prioritization, (ii) a decrease of $5.5 million in personnel-related expenses related to the reduction in workforce and strategic pipeline prioritization, (iii) a net decrease of $3.1 million in external CMO and CRO activities, driven by a decrease of (a) $3.5 million due to timing of CMO activities, and an increase of (b) $0.4 million in CRO activities for our clinical trials, (iv) a decrease of $2.1 million in expenses related to licenses, sublicensing revenue, and milestones, and (v) a decrease of $1.2 million in other facilities and allocated expenses.
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.
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.
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.
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 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 expect that our general and administrative expenses will increase in the future as a result of expanding our operations, including hiring personnel, preparing for potential commercialization of our product candidates, and additional facility occupancy costs, as well as other expenses necessary to support the growth and operations of a clinical-stage public company.
We expect that our general and administrative expenses will increase in the future if our clinical trials are successful and if we prepare for potential commercialization of our product candidates, to support the growth and operations of a public company with late-stage clinical programs and potential commercial products.
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.
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.
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.
Each of these payments results in licensing and collaboration revenue. Revenue under such licensing and collaboration agreements was $11.2 million and $10.0 million for the years ended December 31, 2025, and 2024, respectively.
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 was primarily driven by lower cash utilized for purchases of marketable securities; partially offset by a decrease in proceeds from maturities of marketable securities. Cash Provided by Financing Activities Net cash provided by financing activities was $4.8 million for the year ended December 31, 2025, compared to $16.7 million for the year ended December 31, 2024.
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”).
Changes in these assumptions used could materially affect our financial condition and results of operations. 114 Table of Contents 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.
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.
This decrease was primarily related to a decrease of $4.7 million in legal expenses, including $3.9 million related to the accrual of a securities class action litigation settlement expense in 2024 and a decrease of $3.3 million in personnel-related expenses related to the reduction in workforce and strategic pipeline prioritization.
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.
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.
We may seek to raise any necessary additional capital through a combination of equity offerings (including our at-the-market equity offering program), debt financings, collaborations and strategic alliances, licensing arrangements, or other sources.
Until such time, if ever, that we can generate significant revenue from product sales, we expect to finance our operations through equity offerings (including our at-the-market equity offering program), debt financings, new strategic collaborations, structured or other non-dilutive financings, licensing arrangements, and/or other sources.
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.
Other (Expense) Income Total other (expense) income decreased by $17.8 million for the year ended December 31, 2025, as compared to the year ended December 31, 2024. Impairment of equity investment was $9.2 million related to our equity investment in Edge for the year ended December 31, 2025, compared to zero for the year ended December 31, 2024.
Jefferies uses commercially reasonable efforts consistent with its normal sales and trading practices to sell shares from time to time, based upon our instructions (including any price or size limits or other customary parameters or conditions we may impose).
Jefferies has agreed to use commercially reasonable efforts consistent with its normal sales and trading practices to sell shares from time to time, based on our instructions (including any price or size limits or other customary parameters or conditions we may impose). 109 Table of Contents During the year ended December 31, 2025, we sold 1,644,228 shares of our common stock, in a series of sales, at an average price of $2.60 per share, in accordance with the ATM Sales Agreement and the 2025 Shelf Registration Statement for aggregate gross proceeds of $4.3 million ($4.1 million net of offering expenses).
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.
This decrease was due to (i) changes in the components of net loss primarily related to (a) increase in non-cash charges primarily for impairment charges and impairment of equity investment incurred for the year ended December 31, 2025, and (b) decreases in research and development expenses and general and administrative expenses; and (ii) an increase in net changes in our operating assets and liabilities primarily related to increases in net changes in other assets, prepaid expenses and other current assets, and accounts payable partially offset by a decrease in net changes of accrued expenses and other current liabilities. 112 Table of Contents Cash Provided by Investing Activities Net cash provided by investing activities was $102.2 million for the year ended December 31, 2025, compared to $86.6 million for the year ended December 31, 2024.
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.
See Note 3 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information. 108 Table of Contents Other income, net decreased by $8.7 million for the year ended December 31, 2025, compared to December 31, 2024.
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.
This decrease was primarily related to a $7.2 million decrease in interest income earned from marketable securities and a $1.4 million decrease in gain recognized related to the change in the fair value of the MSKCC success payments liability.
If we are unable to obtain adequate financing when needed, we may have to delay, reduce the scope of, or suspend one or more of our preclinical studies, clinical trials, research and development programs, and/or commercialization efforts.
If we are unable to raise capital as and when needed or on attractive terms, we may have to significantly delay, reduce, or discontinue the development and commercialization of our product candidates or scale back or terminate our pursuit of new in-licenses and acquisitions.
The Shelf Registration Statement was declared effective by the SEC on August 16, 2022, and will expire after three years.
On May 8, 2025, in anticipation of the expiration of the 2022 Shelf Registration Statement on August 16, 2025, we filed a new shelf registration statement on Form S-3 (“2025 Shelf Registration Statement”), which was declared effective by the SEC on May 14, 2025.
Removed
Under these agreements, we license rights to certain intellectual property controlled by us.
Added
See Notes 5 and 7 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information. 104 Table of Contents For the foreseeable future, we expect substantially all our revenue will be generated from licensing and collaboration agreements.
Removed
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.
Added
The following table summarizes our research and development expenses for the periods indicated: Year Ended December 31, 2025 2024 Change (in thousands) External costs: Expenses related to licenses, sublicensing revenue, and milestones $ 2,720 $ 4,828 $ (2,108) Services provided by CROs, CMOs, and third parties that conduct preclinical studies and clinical trials on our behalf 46,183 49,261 (3,078) Other research and development expenses 14,799 23,560 (8,761) Total external costs 63,702 77,649 (13,947) Internal costs: Personnel-related expenses 33,983 39,531 (5,548) Facilities and other allocated expenses 11,754 12,973 (1,219) Total internal costs 45,737 52,504 (6,767) Total research and development expenses $ 109,439 $ 130,153 $ (20,714) 106 Table of Contents 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.
Removed
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.
Added
Impairment Charges Impairment charges consist of charges related to the strategic pipeline prioritization with workforce and cost reduction initiatives announced on April 24, 2025, and include impairment of our leasehold improvements, right of use assets, and lab equipment. See Note 15 to our consolidated financial statements included elsewhere in this Annual Report on Form 10-K for additional information.
Removed
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.
Added
Other (Expense) Income Other (expense) income consists primarily of impairment of an equity investment, 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 the now-terminated Exclusive License Agreement, dated November 13, 2020, with MSKCC (as amended, “MSKCC Agreement”).
Removed
As of December 31, 2024, we had cash, cash equivalents, and marketable securities of $249.4 million. On August 9, 2022, we filed a universal shelf registration statement on Form S-3 (“Shelf Registration Statement”) with the U.S.
Added
Results of Operations Comparison of the Years Ended December 31, 2025, and 2024 The following table summarizes our results of operations for the periods indicated: Years Ended December 31, Change 2025 2024 $ (in thousands) Licensing and collaboration revenue $ 11,159 $ 9,994 $ 1,165 Operating expenses: Research and development 109,439 130,153 (20,714) General and administrative 37,914 46,457 (8,543) Impairment charges 12,150 — 12,150 Total operating expenses 159,503 176,610 (17,107) Loss from operations (148,344) (166,616) 18,272 Other (expense) income Impairment of equity investment (9,158) — (9,158) Other income, net 8,827 17,502 (8,675) Total other (expense) income (331) 17,502 (17,833) Net loss before benefit from income taxes (148,675) (149,114) 439 Benefit from income taxes (550) (9) (541) Net loss $ (148,125) $ (149,105) $ 980 107 Table of Contents Licensing and Collaboration Revenue The following table summarizes our revenue by licensee for the years ended December 31, 2025, and 2024: Years Ended December 31, 2025 2024 Change (in thousands) Pfizer, related party (1) 2,487 2,487 — Edge, related party — 1,623 (1,623) Other licensees 8,672 5,884 2,788 Total licensing revenue $ 11,159 $ 9,994 $ 1,165 (1) Pfizer ceased to be a related party as of December 31, 2025.
Removed
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.
Added
Licensing and collaboration revenue increased by $1.2 million to $11.2 million for the year ended December 31, 2025, from $10.0 million for the year ended December 31, 2024.
Removed
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.
Added
This increase is primarily due to a $2.8 million increase related to other licensees, which was partially offset by a $1.6 million decrease in revenue related to the issuance of additional shares of convertible preferred stock received as consideration to us under the Exclusive License Agreement for Veterinary Therapeutics (as amended, “Edge chRDNA License Agreement”) with Edge Animal Health (“Edge”) in the year ended December 31, 2024.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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We do not believe that inflation had a material effect on our results of operations during the year ended December 31, 2024.
We do not believe that inflation had a material effect on our results of operations during the year ended December 31, 2025.
We 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.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk. We had cash, cash equivalents, and marketable securities of $142.8 million and $249.4 million as of December 31, 2025, and December 31, 2024, respectively, consisting of cash, money market funds, government securities, commercial paper, and U.S. Treasury bills.
Removed
Item 7A. Quantitative and Qualitative Disclosures About Market Risk.

Other CRBU 10-K year-over-year comparisons