CRSP 10-K & 10-Q changes, risk factors and insider trading

We have funded our operations through public and private offerings of our equity securities, private placements of our preferred shares, convertible loans and collaboration agreements with strategic partners. While we were profitable for the year ended December 31, 2021 due to an upfront payment associated with our collaboration with Vertex, we are not currently profitable and we do not expect to be profitable in future years. Our prior losses, combined with expected future losses, have had and will continue to have an adverse effect on our shareholders’ deficit and working capital. We anticipate that our expenses will increase substantially if and as we:

continue our clinical trials for our various wholly-owned and partnered programs;

conduct preclinical studies to support U.S. Investigational New Drug, or IND, applications and foreign equivalents and initiate clinical trials for our product candidates;

add operational, financial and management information systems and personnel, including personnel to support our product candidate development;

In addition, we and our partner, Vertex, have received marketing approval for CASGEVY in certain jurisdictions. Under the Amended A&R Vertex JDCA, for the years ended December 31, 2022, 2023 and 2024, we had the option to defer and did defer costs on the CASGEVY program in excess of $110.3 million annually, subject to certain adjustments under certain circumstances. Beginning in 2025, we will no longer have the option to defer such costs on the CASGEVY program.program, Weand, alsoas expecta result, we have incurred increased development and commercialization expenses for the CASGEVY programprogram. andWe expect that such expenses will exceed our share of revenue for the foreseeable future.

As a result of all of the foregoing, we expect to continue to incur significant and increasing operating losses for the foreseeable future. Because of the numerous risks and uncertainties associated with developing geneproduct editingcandidates, including gene-based product candidates, we are unable to predict the extent of any future losses or when we will become profitable, if at all. Even if we do become profitable, we may not be able to sustain or increase our profitability on a quarterly or annual basis.

The development of geneproduct editingcandidates, including gene-based product candidatescandidates, is capital intensive. We expect our expenses to increase in connection with our ongoing activities, particularly as we continue the research and development of, initiate preclinical studies and clinical trials for and seek marketing approval for our product candidates, as well as incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution to the extent that such sales, marketing, manufacturing and distribution are not the responsibility of our collaborators currently or in the future if we obtain marketing approval for any of our product candidates. For example, beginning in 2025, we will no longer have the option to defer certain costs on the CASGEVY program under the Amended A&R Vertex JDCAJDCA, and, as a result, we have incurred increased development and commercialization expenses for the CASGEVY program. We expect that our share of expenses for the development and commercialization of CASGEVY towill increase, and has increased, and that such expenses will exceedexceed, and have exceeded, our share of revenue for the foreseeable future. We may also need to raise additional funds sooner if we choose to pursue additional indications or geographies for our product candidates, investigate new technologies, including delivery modalities, or otherwise expand more rapidly than we presently anticipate. Accordingly, we will need to obtain substantial additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on attractive terms, we would be forced to delay, reduce or eliminate certain of our research and development programs or future commercialization efforts.

the scope, progress, results and costs of clinical trials, drug discovery, preclinical development and laboratory testing for our wholly ownedwholly-owned and partnered product candidates;

the success of our collaborations with Vertex and Sirius;

the extent to which we are obligated to reimburse, or entitled to reimbursement of various expenses, including clinical trial, developmentdevelopment, manufacturing and commercialization costs, under our current or future collaboration agreements, if any;

Our development efforts are ongoing and we have primarily focused our research and development efforts to date on gene editing and other technologies, including CRISPR/Cas9 technology,and next-generation platform technologies, as well as delivery technologies, and our initial product candidates. Our future success depends heavily on the successful development of our next-generation product candidates and other future product candidates. We have invested substantially all of our efforts and financial resources in the development of our proprietary technologies and identification and development of our current product candidates. Our ability to generate product revenue will depend heavily on the successful development and eventual commercialization of our product candidates, which may never occur. For example, while we and our partner, Vertex, have received marketing approvals for CASGEVY in certain jurisdictions, we cannot guarantee we and Vertex will receive additional marketing approvals for CASGEVY or we will receive marketing approvals for our other product candidates in the future, and our research programs, including additional programs subject to current and future collaboration agreements with third parties, may fail to identify potential product candidates for clinical development for a number of reasons or may fail to successfully advance any product candidates through clinical development. Our potential product candidates may be shown to have harmful side effects or may have other characteristics or unforeseeable consequences that may make the product candidates impractical to manufacture, unmarketable, or unlikely to receive marketing approval, or that lead to product-related claims or litigation, including without limitation personal injury or product liability claims, adverse or serious adverse events, regulatory enforcement actions, or product recalls or market withdrawals. Our partner, Vertex, generates product sales from CASGEVY, of which we receive 40% through our collaboration arrangement with Vertex. This amount is currently insufficient to cover program expenses and as such, we are responsible for 40% of losses, subject to certain limitations. We currently generate no revenue from sales of any wholly-owned product and we may never be able to again research, develop or commercialize a marketable product.

In addition, if any product candidates encounter safety or efficacy problems, development delays, regulatory issues or other problems, our development plans and business could be significantly harmed. For the reasons described above, among others, regulatory authorities, particularly the FDA, have requested, and may request in the future, additional preclinical studies for genome editing products, such as additional studies related to toxicology, biodistribution or reproductive health, and/or preclinical studies earlier in clinical development compared to other therapeutic modalities. Although to date the FDA has cleared the INDs that we have submitted for certain of our clinical trials, including CTX112 and CTX131, it is possible that the FDA may impose requirements that result in a delay of any of our programs or their regulatory approval. If we are unable to complete any required studies satisfactorily, the FDA or other regulatory authorities could require that we exclude certain patient populations from clinical studies, place our clinical studies on hold, or require us to cease further clinical studies or deny approval of such product candidates. Further, competitors that are developing ex vivo or in vivo products with similar technology may experience problems with their product candidates or programs that could in turn cause us to identify problems with our product candidates and programs, or cause the FDA or other regulatory authorities to impose additional requirements, that could cause us to delay or pause development of our product candidates. Any of these occurrences may harm our ability to identify and develop product candidates, and may harm our business, financial condition, results of operations and prospects significantly. We cannot guarantee that the FDA or other regulatory authorities will not change their requirements in the future or approve amendments to our INDs or equivalent regulatory filings on the timelines we expect.

We aim to develop treatments and therapies for people suffering from serious diseases through transformative gene-based medicines, including ex vivo engineered cell therapies and in vivo therapies. Although there have been significant advances in recent years in the fields of gene therapy and genome editing, including CRISPR/Cas9 gene editing technology, such technologies, including in vivo CRISPR-based genome editing technologies in particular, are relatively new and only a limited number of clinical trials of product candidates based on such gene editing technologies have been commenced and their therapeutic utility is largely unproven. As such it is difficult to accurately predict the developmental challenges we may incur for our product candidates as they proceed through product discovery or identification, preclinical studies and clinical trials. For example, to date, no genome editing in vivo therapy has been approved in the United States, EU or other key jurisdictions. While we and our partner, Vertex, have received marketing approvals for CASGEVY in certain jurisdictions, we cannot guarantee we and Vertex will receive additional marketing approvals for CASGEVY or we will receive marketing approvals for our other product candidates in the future. In addition, because we have only recently commenced clinical trials for certain of our other product candidates, we have not yet been able to fully assess safety in humans. There may be long-term effects from treatment with any product candidates that we develop that we cannot predict at this time. Any product candidates we may develop will act at the level of DNA, and, because animal DNA differs from human DNA, testing of our product candidates in animal models may not be predictive of the results we observe in human clinical trials of our product candidates for either safety or efficacy. Also, animal models may not exist for some of the diseases we choose to pursue in our programs. As a result of these factors, it is more difficult for us to predict the time and cost of product candidate development, and we cannot predict whether the application of our gene editing technology, or any similar or competitive gene editing technologies, will result in the identification, development, and regulatory approval of any products. There can be no assurance that any development problems we experience in the future related to our gene editing technology or any of our research and development programs will not cause significant delays or unanticipated costs, or that such development problems can be solved. Any of these factors may prevent us from completing our preclinical studies or any clinical trials that we may initiate or commercializing any product candidates we may develop on a timely or profitable basis, if at all.

Our Engineered Allogeneic T cell Product Candidates Represent A Novel Approach To Autoimmune and Cancer Treatment That Creates Significant Challenges For Us.

For our autoimmune disease and immuno-oncology programs, we are developing a pipeline of allogeneic T cell product candidates (including, for example, CTX112 and CTX131) that are engineered from healthy donor T cells to express chimeric antigen receptors, or CARs, and are intended for use in any patient with certain autoimmune diseases or cancers. Unlike for autologous chimeric antigen receptor, or CAR T, therapies, for allogeneic CAR T therapies, we are reliant on receiving healthy donor material to manufacture our product candidates. Healthy donor T cells vary in type and quality, and this variation makes producing standardized allogeneic CAR T product candidates challenging and makes the development and commercialization pathway of those product candidates uncertain.

In addition, approved autologous CAR T therapies and those under development have shown frequent rates of cytokine release syndrome, neurotoxicity, serious infections, prolonged cytopenia and hypogammaglobulinemia, and other serious adverse events that have resulted in patient deaths. We expect similar adverse events for our allogeneic CAR T product candidates. Moreover, patients eligible for allogeneic CAR T cell therapies but ineligible for autologous CAR T cell therapies due to aggressive cancer and inability to wait for autologous CAR T cell therapies may be at greater risk for complications and death from therapy.therapy or underlying disease. Our allogeneic CAR T cell product candidates may also cause unique adverse events related to the differences between the donor and patients, such as Graft versus Host Disease, or GvHD, or infusion reactions. GvHD results when allogeneic T cells start recognizing the patient’s normal tissue as foreign.

We have designed our CRISPR/Cas9 gene editing technologyaimed to eliminate the T-cell receptor from the healthy donor T cells using our CRISPR/Cas9 gene editing technology to reduce the risk of GvHD from our product candidates, as well as to remove the class I major histocompatibility complex from the cell surface in order to limit the patient’s immune system from attacking the allogeneic T cells and to improve the persistence of the CAR T cells. However, the gene editing of our product candidates may not be successful in limiting the risk of GvHD or premature rejection by the patient. In addition, results of our autoimmune disease and immuno-oncology clinical trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics.

The FDA, MHRA and the EMA have each expressed interest in further regulating biotechnology, including gene therapy and genetic testing. For example, the EMA advocates for a risk-based approach to the development of a gene therapy product. Agencies at both the federal and state level in the United States, as well as the U.S. congressional committees and other governments or governing agencies, have also expressed interest in further regulating the biotechnology industry. Such action may delay or prevent commercialization of some or all of our product candidates.

Immunotherapy, and its method of action of harnessing the body’s immune system, is powerful and could lead to serious side effects that we only discover in clinical trials. Unforeseen side effects could arise either during clinical development or, if such side effects are rare, after our product candidates have been approved by regulatory authorities and the approved product has been marketed, resulting in the exposure of additional patients. If our technology or technology we in-license from third parties, including CRISPR/Cas9 gene editing technology and gene silencing technology, or delivery modalities we utilize demonstrate a similar effect, we may decide or be required to halt or delay preclinical development, clinical development or commercialization of our product candidates. For example, through internal efforts and external collaborations, we are pursuing the development of multiple delivery technologies, including LNPs, to support our current and future in vivo product candidates. Possible adverse side effects that could occur with treatment with a product or product candidate utilizing such delivery modalities could include an immunologic reaction early after administration which, while not necessarily adverse to the patient’s health, could substantially limit the effectiveness of the treatment. While we have designed our proprietary LNP platform to minimize any LNP vehicle-related toxicities with repeat administration in vivo by engineering amino lipids to avoid the immune system and to be rapidly biodegradable relative to prior LNP formulations, we cannot provide assurances that our product candidates utilizing our proprietary LNP platform or similar other delivery modalities will not activate one or more immune responses giving rise to potential immune reaction related adverse events, like liver toxicities or enzyme elevations.

Any positive results from our preclinical studies or preliminary results from our clinical trials of our product candidates may not necessarily be predictive of the results from required later preclinical studies and clinical trials. For example, for our in vivo product candidates, our proposed delivery modalities combined with or separate from our product candidates, have a limited history of being evaluated in human clinical trials. Any of our product candidates, including our in vivo candidates, candidates CTX310utilizing siRNA and CTX320 and our CAR T candidates, CTX112 and CTX131, may fail to show the desired safety and efficacy in later stages of clinical development despite having successfully advanced through initial clinical trials. Preliminary, interim and top-line data from clinical trials may change as more patient data become available. Preliminary, interim or top-line data from clinical trials are not necessarily predictive of final results, including the results submitted in support of approval in a BLA or equivalent submission outside the United States. Interim, top-line and preliminary data remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously announced. As a result, preliminary, interim and top-line data should be viewed with caution until the final data are available. Material adverse changes in the final data compared to the interim data could significantly harm our business prospects. Moreover, preliminary, interim and top-line data are subject to the risk that one or more of the clinical outcomes may materially change as more patient data become available when patients mature on study, patient enrollment continues or as other ongoing or future clinical trials with a product candidate further develop. For example, consistent with the FDA's recommendation, certain of our clinical trials include a 15 year follow-up observation period in which we will continue to collect patient data.

Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in late-stage clinical trials after achieving positive results in early-stage development and we cannot be certain that we will not face similar setbacks. Similarly, many companies in the pharmaceutical and biotechnology industries have failed to receive regulatory approval despite completing registrationregistrational trials. These setbacks have been caused by, among other things, preclinical and other nonclinical findings made while clinical trials were underway or safety or efficacy observations made in preclinical studies and clinical trials, including previously unreported adverse events. Moreover, preclinical, nonclinical and clinical data are often susceptible to varying interpretations and analyses and many companies that believed their product candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain FDA or EMA approval.

In general, the FDA requires the successful completion of two pivotal trials to support approval of a BLA, but in certain circumstances, will approve a BLA based on only one pivotal trial; and our ability to submit and obtain approval of a BLA is ultimately an FDA review decision, which will be dependent upon the data available at such time, and the available data may not be sufficiently robust from a safety and/or efficacy perspective to support the submission or approval of a BLA. For example, there is no assurance that data obtained at the completion of any of our clinical trials, including for our ongoing wholly-owned product candidates, including CTX112 and CTX131, will indicate clinically meaningful benefit or support submission of a BLA, or will be sufficiently robust from a safety and/or efficacy perspective to support either accelerated or conditional approval or full approval. Moreover, there is no assurance that the data obtained to date in the ongoing clinical trials of CASGEVY and being submitted or planned to be submitted is or will be sufficiently robust from a safety and/or efficacy perspective to support either accelerated or conditional approval or full approval of a BLA or a foreign equivalent in all jurisdictions for which regulatory applications are submitted. Depending on the outcome of these ongoing clinical trials and robustness of the data submitted, once submitted, the FDA may require that we conduct additional or larger pivotal trials before we can submit or obtain approval of a BLA. Furthermore, if any undesirable or unacceptable side effects, unexpected characteristics or other serious adverse events occur, and if we are unable to demonstrate such adverse events were caused by factors other than our product candidate, the FDA could suspend our clinical trial until we are able to gather sufficient information or order us to cease further clinical studies of our product candidate. If this were to occur this would likely result in delays in our ability to submit a BLA for regulatory approval. We may face similar challenges with foreign regulatory authorities.

In order to eventually market any of our product candidates in any particular jurisdiction, we must establish and comply with numerous and varying regulatory requirements on a jurisdiction-by-jurisdiction basis regarding safety and efficacy. Approval by the FDA in the United States, if obtained, does not ensure approval by regulatory authorities in other countries or jurisdictions. Similarly, approval by foreign regulatory authorities does not ensure approval by the FDA. In addition, data from clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country. Approval processes vary among countries and can involve additional product testing and validation and additional administrative review periods. Seeking regulatory approval in multiple jurisdictions could result in difficulties and costs for us and require additional preclinical studies or clinical trials which could be costly and time-consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our products in certain countries. Regulatory approval processes outside the United States involve all of the risks associated with FDA approval. We do not have any wholly-owned product candidates approved for sale in any jurisdiction, including international markets, and, as a company, do not have experience in being solely responsible for obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed, our target market will be reduced and our ability to realize the full market potential of our products will be unrealized.

Breakthrough Therapy Designation, Fast Track Designation, Regenerative Medicine Advanced Therapy Designation or Priority Review by the FDA, or PRIME Scheme by the EMA, Even If Granted for Any of Our Product Candidates, May Not Lead to a Faster Development, Regulatory Review or Approval Process, and It May Not Increase the Likelihood That Any of Our Product Candidates Will Receive MarkingMarketing Approval.

We have obtained and may seek RMAT designation for some of our product candidates. For instance, CASGEVY was granted RMAT designation by the FDA for the treatment of TDT and SCD, as well as CTX112zugo-cel for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma. There is no assurance that we will be able to obtain RMAT designation for other of our product candidates. RMAT designation does not change the FDA's standards for product approval, and there is no assurance that such designation will result in expedited review or approval or that the approved indication will not be narrower than the indication covered by the designation. Additionally, RMAT designation can be revoked if the criteria for eligibility cease to be met as clinical data emerges.

Generally, if a product candidate with an orphan drug designation receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the FDA or the European CommissionEMA from approving another marketing authorization application for a product that constitutes the same drug (or, in the EU, a “similar medicinal product”) treating the same indication for that marketing exclusivity period, except in limited circumstances. If another sponsor receives such approval before we do (regardless of our orphan drug designation), we will be precluded from receiving marketing approval for our product for the applicable exclusivity period. The applicable period is seven years in the United States and 10 years in the European Union. The exclusivity period in the United States can be extended by six months if the sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The exclusivity period in the European Union can be extended by two years for medicines that have complied with an agreed pediatric investigation plan prior to authorization of the product. The exclusivity period in the European Union can also be reduced to six years if, at the end of the fifth year, it is established that the product no longer meets the criteria for orphan designation, because, for example, the product is sufficiently profitable so that market exclusivity is no longer justified. Orphan drug exclusivity may be revokedwithdrawn if anythe relevant regulatory agencyauthority determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of patients with the rare disease or condition.

We Expect The Product Candidates We Develop Will Be Regulated Biologics And Therefore They May Be Subject To Competition Sooner Than Anticipated.

Ethical, social and legal concerns about gene therapy could result in additional regulations restricting or prohibiting our products. Even with the requisite approvals from FDA in the United States, the EMAEuropean Commission in the EU and other regulatory authorities internationally, the commercial success of our products or product candidates will depend, in significant part, on the acceptance of healthcare providers, patients and health care payors of gene therapy products in general, and our products or product candidates in particular, as medically necessary, cost-effective and safe. Any product that we commercialize may not gain acceptance by healthcare providers, patients, health care payors and others in the medical community. The degree of market acceptance of gene therapy products and, in particular, our product candidates, if approved for commercial sale, will depend on several factors, including:

the clinical indications for which the product candidate is approved by FDA, the EMAEuropean Commission or other regulatory authorities;

We compete in the segments of the pharmaceutical, biotechnology and other related markets that utilize technologies encompassing genomic medicines to create therapies, including gene editing,editing and gene therapytherapy, nucleic acid therapies, and cell therapy. In addition, we compete with companies working to develop therapies in areas related to our specific research and development programs. Our platform and product focus is on the development of therapies using gene editinggene-based technology, including CRISPR/Cas9, as well as other technologies, including next-generation editing technologies for targeted gene correction and gene insertion with non-viral delivery approaches. For a detailed discussion of the competition that we face with respect to our business, including our platform, product indications, other technologies (e.g. small molecule, antibody, or protein therapies), gene editing technology, gene or cell therapies, intellectual property, new technologies, personnel, clinical trial locations, reimbursement opportunities and collaborators, please see the section entitled “Business—Competition”. If we are unable to compete successfully in this highly competitive biopharmaceutical industry, our business, financial condition and results of operations could be materially adversely affected.

There may be significant delays in obtaining reimbursement for newly approved products, and reimbursement coverage may be more limited than the purposes for which the product is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for reimbursement does not imply that any product will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale, and distribution. Interim reimbursement levels for new products, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the product and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost products and may be incorporated into existing payments for other services. Net prices for products may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of products from countries where they may be sold at lower prices than in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our inability to promptly obtain coverage and profitable payment rates from both government-funded and private payors for any approved products we may develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products, and our overall financial condition. For additional information, see the sections entitled “Business—Coverage, Pricing and Reimbursement” and “Business—Healthcare Reform.” See also, “Risk Factors—Risks Related to Our Relationships with Third Parties—We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CAGEVYCASGEVY Program.”

WeSubject to the terms set forth in the A&R Vertex JDCA, we are obligated to share equally the net profits and net losses, as applicable, incurred under the Amended A&R Vertex JDCA with respect to all product candidates and products specified in the A&R Vertex JDCA other than for CASGEVY. With respect to CASGEVY only, beginning in July 2021, the net profits and net losses are allocated 40% to CRISPR and 60% to Vertex. Vertex has had and may again have additional expenditures related to the CASGEVY program or other programs under the Amended A&R Vertex JDCA that we cannot predict and that we will be required to pay our portion of or agree to pay a portion of in the future pursuant to the terms of the agreement. For example, under certain circumstances, either party can propose to in-license intellectual property that it believes is necessary or commercially reasonable to obtain to develop and commercialize CASGEVY or future hemoglobinopathies product candidates that are subject to the Amended A&R Vertex JDCA, and any costs associated with acquiring such intellectual property rights would be shared by the parties in accordance with the terms of the Amended A&R Vertex JDCA. Moreover, under the Amended A&R Vertex JDCA, for the years ended December 31, 2022, 2023 and 2024, we had the option to defer and did defer costs on the CASGEVY program in excess of $110.3 million annually, subject to certain adjustments under certain circumstances. Beginning in 2025, we will no longer have the option to defer such costs on the CASGEVY program. As a result, our expenses in 2025 related to the CASGEVY program may beare significantly greater than in 2022, 2023 and 2024 as a result of Vertex’s commercialization efforts for CASGEVY.CASGEVY and may be significantly greater than in 2022, 2023 and 2024 in the future.

We have entered into strategic collaborations and license agreements and may enter into additional collaborations and license agreements with third parties in the future. For example, we have entered into a series of agreements with Vertex that contemplate certain research, development, manufacturing and commercialization activities involving various targets. Pursuant to these agreements, Vertex has sole authority to conduct certain activities. For instance, under our 2015 Collaboration Agreement with Vertex, Vertex had sole authority to select genetic targets to pursue and we do not have control over the development of any product candidates for the selected genetic targets. In addition, under our 2019 Collaboration Agreement with Vertex, Vertex has sole authority to develop and commercialize products for the treatment of DMD and DM1 under the agreement (subject to our option to co-develop and co-commercialize products for the treatment of DM1). Some of these collaborations and license agreements provide us with important technologies in order to more fully develop our product candidates and we may enter into collaborations and license agreements with third parties in the future to provide us with important technologies or funding for our programs. The success of these arrangements will depend heavily on the efforts and activities of our collaborators and licensing partners.

Collaborators generally have significant discretion in determining the efforts and resources that they will apply to these collaborations and collaborators may not perform their obligations as expected. For some programs, we also depend on, or may in the future depend on, third-party collaborators and strategic partners to design and conduct our clinical trials, and for any approved products, the commercialization of such products. In some situations, we may not be able to influence our collaboration partners’ decisions regarding the development and commercialization of our partnered product candidates, and as a result, our collaboration partners may not pursue or prioritize the development and commercialization of those partnered product candidates in a manner that is in our best interest or may not be fiscally disciplined in their execution. For example, certain of our agreements allow for the parties under certain circumstances to in-license intellectual property that such believes is necessary or commercially reasonable to obtain to develop and commercialize applicable product candidates, and any costs associated with acquiring such intellectual property rights would be shared by the parties in accordance with the terms of the applicable collaboration or license agreement. Disagreements between parties to a collaboration arrangement regarding clinical developmentdevelopment, manufacturing and commercialization matters can lead to delays in the development process or commercializing the applicable product candidate and, in some cases, termination of the collaboration arrangement or result in litigation or arbitration, which would be time-consuming and expensive. If one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception and reputation in the business and financial communities could be adversely affected.

Licensors generally have sole discretion in determining the efforts and resources that they will apply to the licensed products. In addition, if any of these collaborators or strategic partnerslicensors withdraw support for ourlicensed programs or proposed products or otherwise impair their development or commercialization, our business could be negatively affected. Additionally, if one of our collaboratorslicensors terminates its agreement with us, we may find it more difficult to attract new license partners and our perception in the business and financial communities could be adversely affected.

If conflicts arise between our corporate or academic licensors, collaborators or strategic partners and us, the other party may act in a manner adverse to us and could limit our ability to implement our strategies. Some of our academic collaborators and strategic partners are conducting multiple product development efforts within each area that is the subject of the collaboration with us. Our collaborators or strategic partners, however, may develop, either alone or with others, products in related fields that are competitive with the products or potential products that are the subject of these collaborations. Competing products, either developed by the collaborators or strategic partners or to which the collaborators or strategic partners have rights, may result in the withdrawal of partner support for our product candidates.

CurrentIn addition, current or future collaborators or strategic partners could also become our competitors in the future. Our collaborators or strategic partners could develop competing products, preclude us from entering into collaborations with their competitors, fail to obtain timely regulatory approvals, terminate their agreements with us prematurely, or fail to devote sufficient resources to the development and commercialization of products. Any of these developments could harm our product development efforts.

Our collaborators or strategic partners may adopt alternative technologies, which could decrease the marketability of our gene-editing technology, including CRISPR/Cas9Cas9, geneor editingother technology.technologies. Additionally, because our current collaborators or strategic partners are and we anticipate that any future collaborators or strategic partners will be working on more than one development project, they could choose to shift their resources to projects other than those they are working on with us. If they do so, this would delay our ability to test our technology and would delay or terminate the development of potential products based on our technology, including CRISPR/Cas9 gene editing technology. Further, our collaborators and strategic partners may elect not to develop products arising out of our collaborative and strategic partnering arrangements or to devote sufficient resources to the development, manufacturing, marketing or sale of these products. For example, ViaCyte (a wholly ownedwholly-owned subsidiary of Vertex) elected to opt-out of our diabetes collaboration in 2023. As a result, following such opt-out, we are solely responsible for the costs associated with our diabetes program and we will owe ViaCyte certain opt-out royalties pursuant to the ViaCyte JDCA, which will increase our expenses. Furthermore, the failure to develop and commercialize a product candidate pursuant to our agreements with our current or future collaborators would prevent us from receiving future milestone and royalty payments which would negatively impact our financial results.

We Rely On and Expect To Rely On Third Parties To Conduct Our Clinical Trials And Certain Aspects Of Our Preclinical Studies For Our Product Candidates. If These Third Parties Do Not Successfully Carry Out Their Contractual Duties, Comply With Regulatory Requirements Or Meet Expected Deadlines, We May Not Be Able To Obtain Regulatory Approval For Or Commercialize Our Product Candidates And Our Business Could Be Substantially Harmed.

We and our CROs are and will continue to be required to comply with regulations, including GCPs, for conducting, monitoring, recording and reporting the results of preclinical studies and clinical trials to ensure that the data and results are scientifically credible and accurate and that the trial patients are adequately informed, among other things, of the potential risks of participating in clinical trials and their rights are protected. These regulations are enforced by the FDA, the Competent Authorities of the Member States of the European Economic Area and comparable regulatory authorities for any drugs in clinical development. The FDA enforces GCP regulations through periodic inspections of clinical trial sponsors, principal investigators and trial sites. If we or our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and FDA or comparable regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that, upon inspection, the FDA will determine that any of our future clinical trials will comply with GCPs. In addition, our future clinical trials must be conducted with product candidates produced in accordance with the requirements in cGMP regulations. Our failure or the failure of our CROs to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process and could also subject us to enforcement action and require significantly greater expenditures.

Our Relationships With Healthcare Providers, Physicians, And Third-party Payors Are Subject To Applicable Anti-kickback, Fraud And Abuse And Other Healthcare Laws And Regulations, Which Could Expose Us To Criminal Sanctions, Civil Penalties, Exclusion From Government Healthcare Programs, Contractual Damages, Reputational Harm And Diminished Profits And Future Earnings.

Gene Editing and Gene Silencing Products Are Novel And May Be Complex And Difficult To Manufacture. We Could Experience Manufacturing Problems Or Regulatory Requirements That Result In Delays In The Development, Approval Or Commercialization Of Our Product Candidates Or Otherwise Harm Our Business.

The manufacturing process used to produce ex vivo engineered cell therapies and in vivo genome editing products based on gene-editing technology, including CRISPR/Cas9Cas9, genomeas editingwell technologyas siRNA product candidates are novel, may be complex, and there is limited industry experience implementing and executing such processes to meet clinical and commercial production demand. Several factors could cause production interruptions, including inability to develop novel manufacturing processes, equipment malfunctions, facility contamination, raw material shortages or contamination, natural disasters, including pandemics, disruption in utility services, human error or disruptions in the operations of our suppliers, including acquisition of a supplier by a third party or declaration of bankruptcy. The expertise required to manufacture these product candidates may be unique to a particular third-party contract manufacturing organization, and as a result, it would be difficult and time consuming to find an alternative third-party contract manufacturing organization. Failure or process defects in any of the interrelated systems at either our manufacturing facility or those of our third-party manufacturers, could adversely impact our ability to manufacture and supply cell therapy product candidates and certain components thereof intended for research, clinical and, if approved, commercial production. In addition, we may rely on third-party contract manufacturers outside the United States for certain components of our product candidates, and may be subject to importation regulations that may affect our ability to manufacture or increase the cost of our product candidates.

Our product candidates require and will continue to require processing steps that are more complex than those required for most small molecule drugs. Moreover, unlike small molecules, the physical and chemical properties of biologics generally cannot be fully characterized. As a result, assays of the finished product may not be sufficient to ensure that the product or product candidate will perform in the intended manner. Accordingly, we will employ multiple steps to control the manufacturing process to assure that the process works and the product candidate is made strictly and consistently in compliance with the process. Problems with the manufacturing process, even minor deviations from the normal process, could result in product defects or manufacturing failures that result in lot failures, product recalls, product liability claims or insufficient inventory, or other supply disruptions. If microbial, viral or other contaminations are discovered in our product candidates or in the manufacturing facilities in which our product candidates are made, production at such manufacturing facilities may be interrupted for an extended period of time to investigate and remedy the contamination. We may encounter problems achieving adequate quantities and quality of clinical grade materials that meet FDA, the EMA or other applicable standards or specifications with consistent and acceptable production yields and costs.

In addition, the FDA, the EMA and other health regulatory authorities may require us to submit samples of any lot of any approved product together with the protocols showing the results of applicable tests at any time. Under some circumstances, the FDA, the EMA or other regulatory authorities may require that we not distribute a lot until the relevant agency authorizes its release. Slight deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls. Lot failures could cause us to delay product launches or clinical trials and we may need to conduct product recalls, all of which could be costly to us and otherwise harm our business, financial condition, results of operations and prospects. Problems in our manufacturing process could restrict our ability to meet market demand for our products.products or supply our clinical trials.

Our partner, Vertex, is the manufacturer and exclusive license holder of CASGEVY. For additional information regarding the manufacture of CASGEVY, please see “Risk Factors—Risks Related to Our Relationships with Third Parties—We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CAGEVYCASGEVY Program.”

We and the third-party manufacturers of our product candidates are subject to applicable regulatory requirements, known as current Good Manufacturing Practice, or cGMPs, prescribed by the FDA and other rules and regulations prescribed by the EMA and other regulatory authorities. To obtain FDA and EMAEuropean Commission approval for our product candidates in the United States, Europe and other regions around the world, we need to undergo strict pre-approval inspections of our or our third-party manufacturing facilities. When inspecting our or our contractors'contractors’ manufacturing facilities, the FDA, EMAcompetent authorities of the EU Member States or other regulatory authorities might cite cGMP deficiencies, both minor and significant, which we may not be required to disclose. Remediating deficiencies can be laborious and costly and consume significant periods of time. Moreover, if the FDA, EMAcompetent authorities of the EU Member States or otheranother regulatory authority notes deficiencies as a result of its inspection, it will generally reinspect the facility to determine if the deficiency has been remediated to its satisfaction. The FDA, EMAcompetent authorities of the EU Member States or other regulatory authorityauthorities may note further deficiencies as a result of its reinspection, either related to the previously identified deficiency or otherwise. If we or the manufacturers of our product candidates cannot satisfy the FDA, EMAcompetent authorities of the EU Member States and other regulatory authorities as to compliance with cGMP on a timely basis, marketing approval for our product candidates could be seriously delayed, which in turn would delay commercialization of our product candidates.

Although we have established internal manufacturing capabilities and have established our own cell therapy manufacturing facility, we still rely on outside vendors to manufacture suppliessupplies, critical components and process our product candidates in connection with any clinical trialtrials we undertake of such product candidates. We have not yet caused any product candidates to be manufactured or processed on a commercial scale and may not be able to do so for any of our product candidates. We will make changes as we work to optimize the manufacturing process, and we cannot be sure that even minor changes in the process will result in therapies that are safe and effective.

The facilities used to manufacture our product candidates must be evaluated by the FDA, or other regulatory agencies in other jurisdictions, pursuant to inspections that will be conducted after we submit an application to the FDA or other regulatory agencies. We may not control the manufacturing process of, and will be completely dependent on, our contract manufacturing partners for compliance with regulatory requirements, known as cGMP requirements,requirements for manufacture of our product candidates, as well as critical components for such product candidates. If our third-party contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or other regulatory authorities, they will not be able to secure and/or maintain regulatory approval for their manufacturing facilities or regulatory authorities may cite them for deficiencies, and we may not be able to obtain or may be delayed in obtaining regulatory approval from the FDA or other regulatory authorities for our product candidates. In addition, we have no direct control over the ability of our third-party contract manufacturers to maintain adequate quality control, quality assurance and qualified personnel. If the FDA or a comparable regulatory authority does not approve these facilities or cites these facilities for deficiencies for the manufacture of our product candidates or if it withdraws any such approval or cites deficiencies in the future, we may need to find alternative manufacturing facilities, which would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved. In addition, if our third-party contract manufacturers are unable to timely perform or become distracted as a result of actions taken by the FDA or a comparable regulatory authority, we may experience manufacturing delays or may need to find alternative manufacturing facilities, which in each case, would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.

OurIn addition, our reliance on a limited number of third-party manufacturers exposes us to a number of risks, including the following:

a change in manufacturers or certain changes in manufacturing processes/ and procedures will require that we conduct a manufacturing comparability study to verify that any new manufacturer or manufacturing process/processes and procedures will produce our product candidate according to the specifications previously submitted to the FDA or other regulatory authority, and such study may be unsuccessful;

Our mission is to create transformative gene-based medicines for serious human diseases. We are a leading gene editingbiopharmaceutical company focused on the development of CRISPR-based therapeutics, including by using CRISPR/Cas9 technology. CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA. We aim to apply this technology to disrupt, delete, correct and insert genes to treat genetic diseases and to engineer advanced cellular therapies. We have advanced this technology from discovery to an approved medicine with unparalleled speed, culminating in the landmark first approval of a CRISPR-based therapy, CASGEVY (exagamglogene autotemcel [exa-cel]), in 2023 with our collaborators at Vertex Pharmaceuticals Incorporated, or Vertex. We have established a portfolio of therapeutic programs spanning four core franchises: hemoglobinopathies, in vivo approaches, CAR T, in vivo approaches and typeregenerative 1 diabetes.medicine. Depending on the program, we take either an ex vivo approach, in which we edit cells outside of the human body before administering them to the patient, or an in vivo editing approach, where we deliver the CRISPR-based therapeutic directly to target cells within the human body.

We continue to innovate on our platform to develop next-generation technologies that can enable new therapies. We are developing other technologies, including delivery technologies and other gene editing technologies, like SyNTase. Through our efforts, we aim to unlock the full potential of CRISPR-basedgene-based therapeutics to create medicines that can transform people'speople’s lives. We believe that our innovative research, translational expertise, and clinical development experience, position us as a leader in the development of CRISPR-based therapeutics and may enable us to create an entirely new class of highly effective and potentially curative therapies for patients with both rarecommon and commonrare diseases for whom current biopharmaceutical approaches have had limited success.

In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world. To date, CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland, Kingdom of Saudi Arabia, Kingdom of BahrainSwitzerland and certain countries in the UnitedMiddle Arab EmiratesEast for the treatment of eligible patients 12 years and older with SCD or TDT. We and Vertex continue to investigate CASGEVY, including (1) threein clinical trials designed to assess the safety and efficacy of a single dose of CASGEVY in patients 12 to 35 years of age with severe SCD and TDT, respectively, (2) two clinicalpivotal trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and (3) long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion. Overall, CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of this therapy as a potential one-time functional cure for people with severe SCD and TDT.

WeOur believelead CRISPR/Cas9 has the potential to create the next generation of CAR T cell therapies that may have a superiornext-generation product profilecandidate, andzugocabtagene allowgeleucel broader(zugo-cel; patient access compared to current autologous therapies. We are advancing several cell therapy programs for oncology and/or autoimmune indications, including two next-generation allogeneic CAR T programs,formerly CTX112), targeting Cluster of Differentiation 19, or CD19, and CTX131 targeting Cluster of Differentiation 70, or CD70. These product candidates incorporateincorporates edits designed to enhance CAR T potency, reduce CAR T exhaustion and evade the immune system. AnAs additionala editresult inof CTX131 is designed to prevent CAR T cells from killing other CAR T cells. In addition, thesethe next-generation candidatesedits, exhibitzugo-cel exhibits increased manufacturing robustness, with a higher and more consistent number of CAR T cells produced per batch. We are producing CTX112 and CTX131zugo-cel for clinical trials at our internal GMP manufacturing facility in Framingham, Massachusetts. Zugo-cel continues to advance in both autoimmune disease and hematologic malignancies.

Our CRISPR/Cas9 platform enables us to innovate continuously by incorporating incremental edits into next-generation products. We are advancing several additional investigational CAR T programs,programs. includingIn anaddition, autologous,we gene-editedare developing both transient and integrated in vivo CAR T programtherapies by targeting glypican-3T forcells thewith potentialLNPs treatmentand ofleveraging solidour tumors.delivery, mRNA, and gene editing expertise.

While we have made significant progress with our current portfolio of programs, we recognize that we needmay be able to continuebring transformative therapies to even more patients by continuing to innovate to unlock the full powerpotential of gene editing and bring potentially transformative therapies to even more patients.editing. We haveare a dedicated early-stage research team called CRISPR-X that focusesfocused on innovating next-generation editing modalities. CRISPR-XFor isexample, we have developed a proprietary, next-generation, site-specific gene correction platform called SyNTase editing. In addition, we are also developing technologies to enable whole gene correction and insertion via non-viral DNA delivery and all-RNA systems, without requiring homology-directed repair or viral delivery of DNA.systems.

Other Partnerships. We have entered into a number of additional collaborationscollaborations, research and license agreements in other therapeutic areas, including an additional agreementagreements with Vertex including for the treatment of Duchenne muscular dystrophy and myotonic dystrophy type 1, as well as diabetes, and othersothers, including to support and complement our hematopoietic stem cell, CAR T, in vivo and T1Ddiabetes programs and platform, including agreements with: Nkarta, Inc. to develop and commercialize products leveraging donor-derived, gene-edited CAR-NK cells; Capsida Biotherapeutics, Inc. to develop in vivo gene editing therapies delivered with engineered adeno-associated virus vectors; Roswell Park Comprehensive Cancer Center to advance a gene-edited autologous CAR T program against a new target; MaxCyte, Inc. on ex vivo delivery for our hemoglobinopathy and CAR T programs; CureVac AG on optimized mRNA constructs and manufacturing for certain in vivo programs; and KSQ Therapeutics, Inc. on intellectual property for our allogeneic immuno-oncology programs.platform.

We have a history of recurring losses and expect to continue to incur losses for the foreseeable future; however, we have been in a net income position in certain previous years due to certain payments associated with our collaboration and license agreements with Vertex. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase as we continue our current research programs and development activities; seek to identify additional research programs and additional product candidates; conduct initial drug application supporting preclinical studies and initiate clinical trials for our product candidates; pursue business development activities; initiate preclinical testing and clinical trials for any other product candidates we identify and develop; seek regulatory approval for our product candidates; maintain, defend, protect and expand our intellectual property estate; further develop our gene editing platform; hire additional research, clinical and scientific personnel; incur facilities costs associated with such personnel growth; continue to develop internal manufacturing capabilities and infrastructure; and incur additional costs associated with operating as a public company.

We have not generated any revenue to date from sales of any wholly ownedwholly-owned product. No collaboration revenue was recognized for the year ended December 31, 2025. During the years ended December 31, 2024, 20232024 and 2022,2023, we recognized $35.0 million, $370.0 million and $0.4$370.0 million, respectively, of collaboration revenue, which is primarily related to our collaboration and license agreements with Vertex.

For additional information about our revenue recognition policy, see Note 2 and Note 8 of the notes to our auditedthe consolidated financial statements included in this Annual Report on Form 10-K.

costs of services performed by third parties that conduct research and development and preclinical and clinical activities on our behalf;

facility costs, including rent, depreciation and maintenance expenses; and fees and other payments related to acquiring and maintaining licenses under certain of our third-party licensing agreements.

Other incomeIncome (netExpense), Net

Other income, net consists primarily of interest income earned on investments.investments, as well as the change in fair value of corporate equity securities.

Refer to Note 2 of the notes to ourthe consolidated financial statements included in this Annual Report on Form 10-K for a discussion of recent accounting pronouncements.

No collaboration revenue was recognized for the year ended December 31, 2025. Collaboration revenue was $35.0 million for the year ended December 31, 2024,2024 compared to $370.0 million for the year ended December 31, 2023. Collaboration revenue for the year ended December 31, 2024and was related to Vertex'sVertex’s achievement of a $10.0 million research milestone and $25.0 million research milestone under the Non-Ex License Agreement with Vertex in the fourth quarter of 2024. Collaboration revenue for the year ended December 31, 2023 was related to (i) the achievement of a $200.0 million milestone in connection with the approval of CASGEVY under our collaboration with Vertex and (ii) an upfront payment of $100.0 million and a milestone achieved of $70.0 million under the Non-Ex License Agreement with Vertex. Refer to Note 8 of the notes to ourthe consolidated financial statements included in this Annual Report on Form 10-K for a description of revenue recognized related to Vertex.

$7.9$5.6 million of decreased facility expenses primarily driven by lower laboratory-related costs; and $7.3 million of decreased employee-related expenses.

In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world. To date, CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland and certain countries in the Middle EastEast, including the Kingdom of Saudi Arabia, for the treatment of eligible patients 12 years and older with SCD or TDT. Additionally, in July 2026, the FDA approved expanded use of CASGEVY in the United States for the treatment of eligible patients ages 2 years and older with either SCD or TDT. CASGEVY is the first approved genetic therapy indicated for children as young as 2 years for both SCD and TDT. We and Vertex continue to investigate CASGEVY, including in clinical trials designed to assess the safety and efficacy of a single dose of CASGEVY in patients 12 to 35 years of age with severe SCD and TDT, respectively, two pivotal trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion. Overall, CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of this therapy as a potential one-time functional cure for people with severe SCD and TDT.

Our in vivo portfolio includes cardiovascular programs, such as CTX310, directed towards angiopoietin-related protein 3, which is currently in an ongoing Phase 1b clinical trial in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia. In addition, we have initiated Phase 1 clinical trials of CTX340, directed towards angiotensinogen, in patients for the treatment of refractory hypertension and CTX460, directed towards SERPINA1 using our proprietary SyNTase editing platform, for the treatment of alpha-1 antitrypsin deficiency.

In addition, we have a number of earlier stage investigational in vivo programs leveraging gene disruption in the liver for both common and rare diseases, including CTX340, directed towards angiotensinogen for the treatment of refractory hypertension; our next-generation LPA program, CTX321 directed towards LPA, the gene encoding apolipoprotein(a), a major component of lipoprotein(a), or Lp(a), in development for patients with elevated Lp(a), and CTX460, directed towards SERPINA1 using our proprietary SyNTase editing platform, for the treatment of alpha-1 antitrypsin deficiency. CTX340,. CTX321 and CTX460 areis currently in IND/CTA-enabling studies. We are also pursuing additional delivery technologies, including LNPs, for delivery to tissues beyond the liver, including hematopoietic stem cells and T cells.

In autoimmune disease, it is being investigated in ongoing clinical trials designed to assess the safety and efficacy of the product candidate in adult patients across multiple indications, including an initial clinical trial in systemic lupus erythematosus, or SLE, systemic sclerosis, and inflammatory myositis; a second clinical trial in immune thrombocytopenia purpura and warm autoimmune hemolytic anemia; and a third clinical trial in autoimmune neurologic diseases, including progressive multiple sclerosis, neuromyelitis optica spectrum disorder, myelin oligodendrocyte glycoprotein antibody-associated Disease (MOGAD), N-methyl-D-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated Protein 1 (LGI1) autoimmune encephalitis,encephalitis and stiff person syndrome.

We have a history of recurring losses and expect to continue to incur losses for the foreseeable future; however, we have been in a net income position in certain previous years due to certain payments associated with our collaboration and license agreements with Vertex. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase as we continue our current research programs and development activities; seek to identify additional research programs and additional product candidates; conduct initial drug application supporting preclinical studies and initiate clinical trials for our product candidates; pursue business development activities; initiate preclinical testing and clinical trials for any other product candidates we identify and develop; seek regulatory approval for our product candidates; maintain, defend, protect and expand our intellectual property estate; further develop our gene editing platform and other technologies; hire additional research, clinical and scientific personnel; incur facilities costs associated with such personnel growth; continue to develop internal manufacturing capabilities and infrastructure; and incur additional costs associated with operating as a public company.

We have not generated any revenue to date from sales of any wholly-owned product and do not expect to do so in the near future. Revenue recognized for the three and six months ended MarchJune 31,30, 2026 was $10.2 million and $11.6 million, respectively, primarily related to an upfront payment on an immaterial license and collaboration agreement entered into during the second quarter of 2026. Revenue for the three and six months ended June 30, 2025 was not material. For additional information about our revenue recognition policy, see Note 2, “Summary of Significant Accounting Policies,” in our Annual Report on Form 10-K for the year ended December 31, 2025 filed with the SEC on February 12, 2026, as well as Note 6 of the notes to our unaudited condensed consolidated financial statements included in this Quarterly Report on Form 10-Q.

Comparison of three months ended MarchJune 31,30, 2026 and 2025 (in thousands):

Research and development expenses were $68.6$67.2 million for the three months ended MarchJune 31,30, 2026, compared to $72.5$69.9 million for the three months ended MarchJune 31,30, 2025. The following table summarizes our research and development expenses for the three months ended MarchJune 31,30, 2026 and 2025, together with the changes in those items in dollars (in thousands):

The decrease of approximately $3.9$2.7 million was primarily attributable to a decrease in employee-related costs,costs includingand stock-based compensationfacility-related expenses, offset by an increase in externallicense research and development expenses.fees.

General and administrative expenses were $17.2$17.6 million for the three months ended MarchJune 31,30, 2026, compared to $19.3$18.9 million for the three months ended MarchJune 31,30, 2025. The decrease of approximately $2.1$1.3 million was primarily associated with a decrease in employee-related costs.costs, including stock-based compensation expenses.

Collaboration expense, net, was $45.9$40.3 million for the three months ended MarchJune 31,30, 2026, compared to $57.5$45.2 million for the three months ended MarchJune 31,30, 2025. The decrease was primarily attributable to an increase in our share of CASGEVY revenue.

Other income was $8.2$27.1 million for the three months ended MarchJune 31,30, 2026, compared to $13.5$22.1 million of income for the three months ended MarchJune 31,30, 2025. The decreaseincrease of approximately $5.3$5.0 million in other income was primarily due to the change in fair value of corporate equity securities during the three months ended MarchJune 31,30, 2026.

We have predominantly incurred losses and cumulative negative cash flows from operations since our inception. As of MarchJune 31,30, 2026, we had $2,441.8$2,364.4 million in cash, cash equivalents and marketable securities, of which approximately $305.2$308.1 million was held outside of the United States, and an accumulated deficit of $2,070.5$2,161.6 million. We anticipate that we will continue to incur losses for at least the next several years. We expect to continue to incur research and development costs and general and administrative expenses consistent with costs associated with research and development at companies of our size and stage of development, and, as a result, we will need additional capital to fund our operations, which we may raise through public or private equity or debt financings, strategic collaborations, or other sources.

For the three and six months ended MarchJune 31,30, 2025, we issued and sold an aggregate of 0.2 million common shares under the 2021 ATM at an average price of $54.33 per share for aggregate proceeds of $8.7 million, which were net of equity issuance costs of $0.1 million, excluding stamp taxes of $0.1 million.

No common shares were issued and sold under the 2025 ATM for the three and six months ended MarchJune 31,30, 2026. As of MarchJune 31,30, 2026, we issued and sold an aggregate of 0.7 million common shares under the 2025 ATM at an average price of $60.81 per share for aggregate proceeds of $42.3 million, which were net of equity issuance costs of $0.5 million, excluding stamp taxes of $0.4 million. Common shares having aggregate gross proceeds up to $557.2 million remain available under the 2025 ATM.

Our ability to generate revenue and achieve profitability depends significantly on our success in many areas, including: developing our delivery technologies and our gene editing technology platformplatform, as well as our delivery and other technologies; selecting appropriate product candidates to develop; completing research and preclinical and clinical development of selected product candidates; obtaining regulatory approvals and marketing authorizations for product candidates for which we complete clinical trials; developing a sustainable and scalable manufacturing process for product candidates; launching and commercializing product candidates for which we obtain regulatory approvals and marketing authorizations, either directly or with a collaborator or distributor; obtaining market acceptance of our product candidates, either directly or with a collaborator or distributor, if approved, including for CASGEVY; addressing any competing technological and market developments; negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter; maintaining good relationships with our collaborators and licensors; maintaining, defending, protecting and expanding our estate of intellectual property rights, including patents, trade secrets and know-how; and attracting, hiring and retaining qualified personnel.

Net cash used in operating activities was $108.8$192.4 million for the threesix months ended MarchJune 31,30, 2026, compared to $53.9$167.8 million for the threesix months ended MarchJune 31,30, 2025. The $54.9$24.6 million increase in net cash used in operating activities was primarily driven by a $70.3$57.4 million overall decrease in net changes of operating assets and liabilities, primarily driven by the timing of receipt of a $25.0 million milestone payment from Vertex which was paid in the first quarter of 2025, offset by a decrease in net loss of approximately $13.1$130.5 million.

Net cash used in investing activities for the threesix months ended MarchJune 31,30, 2026 was $410.7$466.4 million, compared to net cash usedprovided inby investing activities of $19.8$50.2 million for the threesix months ended MarchJune 31,30, 2025. The increase in net cash used in investing activities was primarily driven by a net increase in purchases of our marketable securities.

Net cash provided by financing activities for the threesix months ended MarchJune 31,30, 2026 was $591.9$599.1 million, compared with $10.6$12.8 million for the threesix months ended MarchJune 31,30, 2025. Net cash provided by financing activities for the threesix months ended MarchJune 31,30, 2026 consisted primarily of $585.4 million in net proceeds from the issuance of the Notes in March 2026.

There have been no material changes in our critical accounting policies and estimates in the preparation of our condensed consolidated financial statements during the three and six months ended MarchJune 31,30, 2026 compared to those discussed in our Annual Report on Form 10-K for the year ended December 31, 2025 filed with the SEC on February 12, 2026, with the exception of the new policy with respect to convertible debt described below.