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

Investing in our common stock involves a high degree of risk. In evaluating us and our business, careful consideration should be given to the following risk factors, in addition to the other information set forth in this Annual Report on Form 10-K for the year ended December 31, 20242025 and in other documents that we file with the SEC.Securities and Exchange Commission (“SEC”). If any of the following risks and uncertainties actually occurs, our business, prospects, financial condition and results of operations could be materially and adversely affected. The risks described below are not intended to be exhaustive and are not the only risks facing us. New risk factors can emerge from time to time, and we cannot predict the impact that any factor or combination of factors may have on our business, prospects, financial condition and results of operations.

CRISPR/Cas9 genome editing technology has only recently been clinically validated for human therapeutic use.

We are focused on developing novel therapeutics utilizing CRISPR/Cas9 genome editing technology, including in vivo therapies and ex vivo engineered cell therapies. Although there have been significant advances in recent years in the fields of gene therapy and genome editing, in vivo CRISPR-based genome editing technologies are relatively new and their therapeutic utility is largely unproven. Our approach to developing therapies centers on using CRISPR/Cas9 technology to alter, introduce or remove genetic information in vivo to treat various disorders, or to engineer human cells ex vivo to create therapeutic cells that can be introduced into the human body to address the underlying disease.

The approaches we are taking to discover and develop novel therapeutics using CRISPR/Cas9 systems are unproven and may never lead to marketable products.

Successful development of products by us will require solving a number of issues, including developing or obtaining technologies to safely deliver a therapeutic agent into target cells within the human body or engineer human cells while outside of the body such that the modified cells can have a therapeutic effect when delivered to the patient, optimizing the efficacy and specificity of such products, and demonstrating the therapeutic selectivity, efficacy, potency, purity and safety of such products. There can be no assurance we will be successful in solving any or all of these issues. With regards to CRISPR/Cas9-basedCRISPR-based therapies specifically, we are in clinical-stage development for nex-znexiguran ziclumeran (“nex-z,” also referred to as NTLA-2001) (pending resolution of the clinical hold on the IND for the MAGNITUDE trial) and for lonvoguran ziclumeran, (“lonvo-z,” also known as NTLA-2002) and advancing towards clinical testing for our other in vivo and ex vivo product candidates. Although one CRISPR/Cas9-editedCRISPR-edited ex vivo therapy has been approved in the United States (“U.S.”) and European Union (“EU”), no genome editing in vivo therapy has been approved in the U.S., EU countries or other key jurisdictions, and the potential to successfully obtain approval for any of our CRISPR/Cas9 product candidates remains uncertain.

Our future success also is highly dependent on the successful development of CRISPR-based genome editing technologies, cellular delivery methods and therapeutic applications for the indications on which we have focused our ongoing research and development efforts. We may decide to alter or abandon these programs as new data become available and we gain experience in developing CRISPR/Cas9-basedCRISPR-based therapeutics. We cannot be sure that our CRISPR/Cas9 efforts and technologies will yield satisfactory products that are safe and effective, sufficiently pure or potent, manufacturable, scalable or profitable in our selected indications or any other indication we pursue. We cannot guarantee that progress or success in developing any particular CRISPR/Cas9-basedCRISPR-based therapeutic product will translate to other CRISPR/Cas9-basedCRISPR-based products.

Successful completion of clinical trials is a prerequisite to submitting a Biologics License Application (“BLA”) to the U.S.United States Food and Drug Administration (“FDA”), and similar applications to comparable foreign regulatory authorities, for each product candidate and, consequently, the ultimate approval and commercial marketing of any product candidates. We do not know whether any of our clinical trials will begin or be completed on schedule, if at all. In addition, the regulatory requirements for later phase clinical trials, such as pivotal trials, are generally more stringent than earlier phase clinical trials, such as Phase 1 trials. We may not meet the requirements of regulatory authorities, such as the FDA, for initiating later phase clinical trials for our product candidates, which could delay the development of our product candidates, including the submission of a BLA or comparable marketing application.

challenges in obtaining regulatory authorization or approval to conduct clinical trials in the U.S. from the FDA through an investigational new drug (“IND”) application or from other regulatory agencies outside the U.S., such as the United Kingdom (“U.K.”) Medicines and Healthcare products Regulatory Agency (“MHRA”) or the European Medicines Agency (“EMA”), through corresponding applications, such as a clinical trial application, a clinical trial notification or a clinical trial exemption, because these agencies have very limited or no experience with the clinical development of CRISPR/Cas9-basedCRISPR-based therapeutics, particularly in vivo therapeutics, which may require additional significant testing or data compared to more traditional therapies or otherwise delay the development of our product candidates;

regulatory agencies may require us to amend our INDsIND applications or equivalent regulatory filings, modify the design of our clinical trials or perform more extensive or lengthier preclinical or clinical testing compared to existing therapeutic modalities, any of which may delay the initiation or progression of any of our clinical trials;

the FDA or other regulatory authorities may require us to submit additional data, such as long-term toxicology studies, or impose other requirements, including submitting preclinical data earlier in clinical development compared to existing therapeutic modalities or requiring amendments to our regulatory filings, before permitting us to initiateinitiate, continue or rely on a clinical trial;

the FDA or other regulatory authorities may revise the requirements for authorizing our clinical trials or approving our product candidates, or their interpretation of the authorization or approval requirements may not be what we anticipate or require us to adopt Risk Evaluation and Mitigation Strategy (“REMS”) as a condition of approval; and we may not ultimately obtain regulatory approval for a BLA, or corresponding applications outside the U.S., such as a marketing authorization application in the U.K. and other similar regulatory authorities, which may have very limited or no experience with the clinical development of CRISPR/Cas9-basedCRISPR-based therapeutics, particularly in vivo therapeutics.

We could also encounter delays if a clinical trial is suspended or terminated by us, the IRBs of the institutions in which such trials are being conducted, the relevant ethics committee or the FDA or other relevant regulatory authorities, or if the Data Monitoring Committee (“DMC”) for such trial recommends such suspension or termination. Such authorities may impose or recommend such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our study protocols, inspection of the clinical trial operations or trial site by the FDA or other regulatory authorities, resulting in the imposition of a clinical hold, manufacturing or quality control issues, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product or treatment, failure to establish or achieve clinically meaningful trial endpoints, or changes in governmental regulations or administrative actionsactions. orFor lackexample, on October 29, 2025, the FDA placed a clinical hold on the IND applications for the MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials for patients with transthyretin (“ATTR”) amyloidosis with cardiomyopathy (“ATTR-CM”) and hereditary ATTR amyloidosis with polyneuropathy (“ATTRv-PN”), respectively. This action followed a report of adequateGrade funding4 toliver continuetransaminase elevations and increased total bilirubin in a patient who was dosed with nex-z in the MAGNITUDE trial, who has since passed away. In January 2026, the FDA removed the clinical hold on the IND application for the MAGNITUDE-2 Phase 3 clinical trial, but we cannot predict when we will resume the MAGNITUDE Phase 3 clinical trial for nex-z, and there is a risk that we may not be able to resume the trial. ManyIf regulatory authorities determine that the case may be indicative of the factorsconcerns that cause, or lead to, a delay in the commencement or completion of clinical trials may also leadapply to aour delay in submitting a BLA or comparable marketing application or ultimately lead to the denial of regulatory approval of ourother product candidates.candidates, Further,it is possible that the FDA or other regulatory authorities may disagreerequest withadditional information, place additional restrictions or requirements, or impose a clinical hold on our clinical trial design and our interpretation of data fromother clinical trials or development programs, or that our licensing partners may changecease clinical development of their licensed assets, until we are able to resolve the requirements for approval even after they have reviewed and commented on the design for our clinical trials.hold.

To date, most human clinical trials utilizing either in vivo or ex vivo CRISPR-based therapeutics are still at a clinical stage, with only one ex vivo CRISPR-based therapeutic product approved in the U.S. and EU. We have ongoing clinical trials in various countries for nex-z for transthyretin (“ATTR”) amyloidosis (pending resolution of the clinical hold on the IND for the MAGNITUDE clinical trial) and NTLA-2002for lonvo-z for hereditary angioedema (“HAE”). There is no certainty that the FDA or other similar agencies will continue to apply to all our CRISPR/Cas9 product candidates the same regulatory pathway and requirements it is applying to other in vivo therapies or ex vivo engineered therapeutics.

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 bodies, 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 the FDA cleared the INDsIND applications that we have submitted, it is possible that the FDA may impose requirements that result in a delay of any of our programs,programs (including our submission of a BLA or comparable marketing application, or their regulatory approval.approval), Ifsuch we are unable to completeas the requiredclinical studieshold satisfactorily,that the FDA orplaced otheron regulatorythe bodiesIND couldapplications requirefor the MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials for patients with ATTR-CM and ATTRv-PN, respectively, in October 2025. While the FDA removed the clinical hold for the IND for the MAGNITUDE-2 trial in January 2026, we cannot predict when we will resume the MAGNITUDE Phase 3 clinical trial for nex-z, and there is a risk that we excludemay certainnot patientbe populations from clinical studies, place our clinical studies on hold, or require usable to cease further clinical studies or deny approval of such product candidates. Further, competitors that are developing in vivo or ex 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 causeresume the FDAtrial orat other regulatory bodies 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.all.

We may experience manufacturing delays or other issues that prevent us from executing the clinical trials for nex-z (pending resolution of the clinical hold on the IND for the MAGNITUDE clinical trial) and NTLA-2002for lonvo-z or our other product candidates on the timeline we expect. Moreover, we cannot guarantee that the FDA, MHRA, the New Zealand Medicines and Medical Devices Safety Authority,EMA, or other regulatory authorities will not change their requirements in the future or that they will approve amendments to our INDsIND applications or equivalent regulatory filings, including for nex-z and NTLA-2002,lonvo-z, or our other product candidates, on the timeline we expect.

Results, including data from our preclinical and clinical studies, are not necessarily predictive of our other ongoing and future preclinical and clinical studies, and they do not guarantee or indicate the likelihood of approval of any potential product candidate by the FDA or any other regulatory agency. If we cannot replicate the positive results from any of our preclinical or clinical activities and studies, we may be unable to successfully develop, obtain regulatory approval for and commercialize any potential product candidate.

From time to time, we may disclose interim data from our clinical trials, such as the interim results of our ongoing Phase 1 study of nex-z or Phase 1/2 study of NTLA-2002.lonvo-z. Interim data from clinical trials that have not been completed are subject to the risk that the later results may be materially different as patient enrollment continues. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Consequently, interim data should be viewed with caution until we make the final data and analysis available.

In addition, there is a high failure rate, as well as potential substantial and unanticipated delays, for product candidates progressing through preclinical and clinical studies. Even if we are able to successfully complete our ongoing and future preclinical and clinical activities and studies for any potential product candidate, we may not be able to replicate, or may have to engage in significant efforts and resource and time investments to replicate, any positive results from these or any other studies in any of our future preclinical and clinical trials, and they do not guarantee approval of any potential product candidate by the FDA or any other necessary regulatory authorities in a timely manner or at all. For more information regarding these risks, see also the remainder of this risk factor section.

Negative public opinion and increased regulatory scrutiny of CRISPR/Cas9 use, genome editing or gene therapy may damage public perception of the safety of our product candidates and adversely affect our ability to conduct our business or obtain regulatory approvals for such product candidates.

Gene therapy in general, and genome editing in particular, remain novel technologies, with only a limited number of gene therapy products, and only one ex vivo genome editing product, approved to date in the U.S. and EU. Public perception may be influenced by claims that gene therapy or genome editing, including the use of CRISPR/Cas9,CRISPR, is unsafe or unethical, or carries an undue risk of side effects, such as improper modification of a gene sequence in a patient’s chromosome that could lead to disease such as cancer, and gene therapy or genome editing may not gain the acceptance of the public or the medical community. In particular, our success will depend upon physicians who specialize in the treatment of diseases targeted by our product candidates prescribing our product candidates in lieu of, or in addition to, existing treatments with which they are more familiar and for which greater clinical data may be available. In addition, responses by the U.S., state or foreign governments to negative public perception or ethical concerns may result in new legislation or regulations that could limit our ability to develop or commercialize any product candidates, obtain or maintain regulatory approval or otherwise achieve profitability. More restrictive statutory regimes, government regulations or negative public opinion could have an adverse effect on our business, financial condition and results of operations and prospects, and may delay or impair the development and commercialization of our product candidates or demand for any products we may develop. For example, certain gene therapy trials led to several well-publicized adverse events, including cases of leukemia and death.death, Seriousand serious adverse events,events suchalso ashave these,occurred in ourconnection with commercial use of approved gene therapies. In October 2025, the FDA placed a clinical trials,hold oron otherthe IND applications for the MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials involvingfor genepatients therapywith ATTR-CM and ATTRv-PN, respectively, following a report of Grade 4 liver transaminase elevations and increased total bilirubin in a patient who was dosed with nex-z in the MAGNITUDE trial. This patient passed away on November 5, 2025. It was reported by the principal investigator that the patient died due to septic shock secondary to a perforated duodenal ulcer. The patient’s complicated clinical course also included acute liver injury and its treatment with corticosteroids. An autopsy report supported the clinical diagnoses. The FDA removed the clinical hold on the IND for the MAGNITUDE-2 clinical trial in January 2026. For more information, see the above risk factor entitled “We may incur additional costs or genome editing products or our competitors’ products, even if not ultimately attributable to the relevant product candidates, and the resulting publicity could result in increased government regulation, unfavorable public perception, potential regulatoryexperience delays in the testingcompleting, or approvalultimately be unable to complete, the development and commercialization of ourany product candidates, stricter labeling requirements for those product candidates that are approved and a decrease in demand for any such product candidate. In addition, the use of genome editing technology by third parties in areas that are not being pursued by us, such as for targeting and editing of embryonic cells, could adversely impact public and governmental perceptions regarding the ethics and risks of CRISPR/Cas9 technology and lead to social or legal changes that could limit our ability to apply the technology to develop human therapies addressing disease. For example, reports of the use of CRISPR/Cas9 in China and Russia to edit embryos in utero have generated, and may continue to generate, negative public perception about the use of the technology in humans. Negative public and governmental perception of the technology, or additional governmental regulation of our technologies, could also adversely affect our stock price or our ability to enter into revenue generating collaborations or obtain additional funding from the public markets.candidates.”

Therapeutic applications of genome editing technologies, and CRISPR/Cas9 in particular, for both in vivo products and ex vivo products, are uncertain and must undergo rigorous clinical trials and regulatory review before receiving marketing authorization. If the results of our clinical studies or those of any other third parties, including with respect to genome editing technology or engineered cell therapies, are inconclusive or fail to show efficacy or if such clinical trials give rise to safety concerns or adverse events, we may:

Additionally, our product candidates could potentially cause other adverse events that have not yet been predicted and the potentially permanent nature of genome editing effects, including CRISPR/Cas9’sCRISPR’s effects, on genes or novel cell therapies in the organs of the human body may make these adverse events irreversible. The inclusion of critically ill patients in our clinical studies or those of our competitors may result in deaths or other adverse medical events, including those due to other therapies or medications that such patients may be using. Any of these events could prevent us from achieving or maintaining regulatory approval or market acceptance of our product candidates and impair our ability to achieve profitability.

We are at a clinical stage of development and our technology and approach has not yet led, and may never lead, to the approval or commercialization of any of our product candidates, including nex-z for ATTR amyloidosis,amyloidosis NTLA-2002(pending resolution of the clinical hold on the IND for the MAGNITUDE clinical trial) and lonvo-z for HAE, or to our other preclinical stage product candidates being deemed appropriate for clinical development and ultimately approval by a regulatory agency. Even if we are successful in building our pipeline of product candidates, completing clinical development, establishing the necessary manufacturing processes and capabilities, obtaining regulatory approvals and commercializing product candidates will require substantial additional funding and are subject to the risks of failure inherent in therapeutic product development. Investment in biopharmaceutical product development involves significant risk that any potential product candidate will fail to demonstrate acceptable safety and efficacy profiles, gain regulatory approval, or become commercially viable.

We cannot provide any assurance that we will be able to successfully advance any of our product candidates, including nex-z,nex-z NTLA-2002(pending resolution of the clinical hold on the IND for the MAGNITUDE clinical trial), lonvo-z, or product candidates developed through our collaborations, through the entire research and development process. Any of our other programs may show promise yet fail to yield product candidates for clinical development or commercialization for many reasons. For more information regarding these risks, see the above risk factor section entitled “Risks Related to Preclinical and Clinical Development.”

The use of the CRISPR/Cas9 system to create genome editing-based therapies is a recent development and may not become broadly accepted by patients, healthcare providers, third party payors and other stakeholders. A variety of factors will influence whether our product candidates are accepted in the market, including, for example:

Even if our products achieve market acceptance, we may not be able to maintain that market acceptance over time if new products or technologies are introduced that are more favorably received than our products, are more cost effective or render our products obsolete. In addition, adverse publicity due to the ethical and social controversies surrounding the therapeutic in vivo use of CRISPR/Cas9,CRISPR, genome edited modified cells, or other therapeutics mediums, such as viral vectors that we may use in our clinical trials may limit market acceptance of our product candidates. If our product candidates are approved but fail to achieve market acceptance among physicians, patients, hospitals, third party payors or others in the medical community, we will not be able to generate significant revenue. Our efforts to educate the healthcare providers, patients and third party payors about our products may require significant resources and may never be successful.

For example, through a license agreement between Caribou Biosciences, Inc. and us (the “Caribou License”), we sublicense the rights of the Regents of the University of California and the University of Vienna (collectively, “UC/Vienna”) to a worldwide patent portfolio that covers methods of use and compositions relating to engineered CRISPR/Cas9 systems for, among other things, cleaving or editing DNA and altering gene product expression in various organisms, including eukaryotic cells. We sublicense the UC/Vienna rights to this patent portfolio for human therapeutic, prophylactic and palliative uses, including companion diagnostics, except for anti-fungal and anti-microbial uses. Because UC/Vienna co-own this portfolio with Dr. Emmanuelle Charpentier (who has separately licensed her rights to other parties), we refer to this co-owned worldwide patent portfolio as the “UC/Vienna/Charpentier patent family.” In addition, we have granted further sublicenses to this portfolio to our collaborators in certain fields of use. The UC/Vienna/Charpentier patent portfolio to-date includes, for example, multiple granted, allowed, and/or allowable patent applications in the U.S., as well as granted patents from the European Patent Office, the United Kingdom’s Intellectual Property Office, the German Patent and Trade Mark Office, Australia’s Intellectual Property agency and China’s Intellectual Property Office, among others.

Third parties could assert, and have in the past asserted, that our licensors do not have rights to the licensed patents and/or patent applications (such as, in the case of the Caribou License, the UC/Vienna/Charpentier patent family), including inventorship and ownership rights to currently issued or allowable patents. In addition, third parties could assert, and have asserted, that our licensors, or any rights owned by our licensors, such as UC/Vienna/Charpentier, are limited. If such third parties were found to have rights to patents or patent applications covering our licensed technology (such as CRISPR/Cas9 technology), they could assert that we infringe such patents and, as discussed above, we may be required to obtain rights from such parties (e.g., by obtaining a license) or cease our development and commercialization efforts. Even if such third parties are not ultimately successful in their claims, such assertions could result in significant costs or delays to our programs.

For example, various patent applications within the UC/Vienna/Charpentier patent family and the Broad Institute patent family have been involved in patent interferences and other patent challenges in the U.S. and other jurisdictions, in which the respective owners have alleged, and are alleging, that they invented and/or own intellectual property claiming overlapping aspects of CRISPR/Cas9 systems. Specifically, certain patent applications within the UC/Vienna/Charpentier patent family, licensed to us under the Caribou License, covering certain aspects of CRISPR/Cas9 systems to edit genes in eukaryotic cells, including human cells (collectively, the “UC/Vienna/Charpentier eukaryotic patent family”) have been the subject of patent interferences involving patents and patent applicationapplications co-owned by the Broad Institute, Massachusetts Institute of Technology, the President and Fellows of Harvard College and the Rockefeller University (collectively, the “Broad Institute”) that also claim CRISPR/Cas9 systems to edit genes in eukaryotic cells (collectively, the “Broad Institute patent family”). For example, onOn June 25, 2019, the Patent Trial and Appeal Board (“PTAB”) of the U.S. Patent and Trademark Office (“USPTO”) declared an interference between the UC/Vienna/Charpentier eukaryotic patent family and the Broad Institute patent family to determine which research group first invented the use of the CRISPR/Cas9 technology in eukaryotic cells and, therefore, is entitled to the U.S. patents covering that invention. The interference involved 14 allowable patent applications from the UC/Vienna/Charpentier eukaryotic patent family and 13 patents and one patent application from the Broad Institute patent family. On February 28, 2022, the PTAB issued a Decision of Priority and Judgment in the interferenceinterference, finding that the Broad Institute patent family has priority over the UC/Vienna/Charpentier patent family with respect to the subject matter of the interference. AnBoth appealparties andfiled cross-appealappeals from the interference are pending atto the United States Court of Appeals for the Federal Circuit as Case Nos. 22-1594 and 22-1653 (the “Interference Appeal”), and the oral argument occurred on May 7, 2024. On May 12, 2025, the Federal Circuit panel issued its decision in the Interference Appeal. The Federal Circuit (a) vacated the PTAB’s finding that the Broad Institute was the first to invent the use of CRISPR technology in eukaryotic cells, (b) returned the case to the PTAB to determine which research group was the first to invent the use of CRISPR technology in eukaryotic cells under the correct legal standard, (c) affirmed the PTAB’s finding that the first application filed by UC/Vienna/Charpentier lacked written description support, and (d) dismissed the Broad Institute’s cross-appeal. After neither party requested rehearing of the Federal Circuit panel’s decision, the mandate issued and the interference was returned to the PTAB for further proceedings.

In addition, on December 14, 2020, the PTAB declared an interference between the same 14 allowable patent applications in the UC/Vienna/Charpentier eukaryotic patent family, and one patent application owned by ToolGen, Inc. And, on June 21, 2021, the PTAB declared another interference between the same 14 allowable patent applications in the UC/Vienna/Charpentier eukaryotic patent family and one patent application owned by Sigma-Aldrich Co. LLC (a subsidiary of Merck KGaA). Because the patent applications involved in these interferences also purport to cover the use of CRISPR/Cas9 for gene editing in eukaryotic cells, the PTAB seeks to determine between the various groups which one invented first and is entitled to the resulting U.S. patents. A decision on motions issued in the ToolGen interference on September 28, 2022, and the priority phase of that interference was suspendedsuspended. untilIn January 2026, in response to a mandatemotion concludesfrom ToolGen seeking to lift the Interferencesuspension, Appeal.the PTAB ordered that the stay in the ToolGen interference will be lifted following a decision on remand in the Broad Interference, and the prevailing party in the Broad interference will then proceed with the priority phase against ToolGen. The Sigma-Aldrich interference is incurrently its motions phase, and an order scheduling oral argument issued on October 24, 2022.stayed. In addition, other third parties, such as Vilnius University (whose patents we have sublicensed under our Caribou Agreement) and Harvard University, filed patent applications claiming CRISPR/Cas9-relatedCRISPR-related inventions around or within a year after the first patent application filed in the UC/Vienna/Charpentier patent family and allege (or may allege) that they invented one or more of the inventions claimed by UC/Vienna/Charpentier before UC/Vienna/Charpentier. If the USPTO deems the scope of any of such third party’s claims sufficiently overlap with the allowable claims from the applicable patent applications in the UC/Vienna/Charpentier patent family, the USPTO could declare other interference proceedings to determine the actual inventor of such claims.

If either the Broad Institute, ToolGen or Sigma-Aldrich were to succeed in any of their respective interferences, or if other third parties, such as Vilnius University or Harvard University, pursue claims and succeed in such claims, the prevailing party or parties could assert its issued patents against us based on our CRISPR/Cas9-basedCRISPR-based activities, including research, development, and commercialization of our product candidates or resulting products. In addition, such claims could result in the loss of rights to certain patents and patent applications in the UC/Vienna/Charpentier patent family and, thus, we (and our sublicensees) could lose the benefits that we obtained under our Caribou License to the UC/Vienna/Charpentier patent family. The prevailing party may also assert similar infringement claims against our existing or potential collaborators, clinical investigators, CMOs, CROs, consultants or vendors, and we may be obligated to defend and/or indemnify those parties against such infringement claims. As discussed above, such allegations or litigation may affect our ability to market and sell CRISPR/Cas9-basedCRISPR-based human therapeutics and may result in significant costs or delays to our programs.

Further, many third parties, including the third parties described above, have also filed patent applications and obtained patents covering aspects of the CRISPR/Cas9 technology in other key jurisdictions, including the EU members, the U.K., China and Japan. If these patents are deemed valid and cover our product candidates or related activities, we could be prevented from developing and/or commercializing all or some of our product candidates, or the resulting products, unless we license the relevant intellectual property or avoid it.

We could be unsuccessful in obtaining or maintaining adequate patent protection for one or more of our products or product candidates,candidates or asserting and defending our intellectual property rights that protect our products and technologies.

The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the U.S. and abroad. There is a substantial amount of litigation as well as administrative proceedings for challenging patents, including interference, derivation, reexamination, and other post-grant proceedings before the USPTO and oppositions and other comparable proceedings in foreign jurisdictions, involving patents and other intellectual property rights in the biotechnology and pharmaceutical industries, and we expect this to be true for the CRISPR/Cas9 space as well. As discussed above, a number of third parties have filed oppositions challenging the validity, and seeking the revocation, of several CRISPR/Cas9 genome editing patents granted to UC/Vienna/Charpentier by the European Patent Office (“EPO”). U.S. law also provides for other procedures to challenge patents, including inter partes reviews, post-grant reviews and, in certain circumstances, interference or derivation proceedings, thatwhich add uncertainty to the possibility of challenge to our developed or licensed patents and patent applications in the future. See the above risk factor entitled “Third party claims of intellectual property infringement against us, our licensors or our collaborators may prevent or delay our product discovery, research, development and/or commercialization efforts.”

We have limited intellectual property rights outside the U.S. Filing, prosecuting, maintaining and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the U.S. can have a different scope and strength than do those in the U.S. In addition, the laws of some foreign countries, such as China, Brazil, Russia, India and South Africa, do not protect intellectual property rights to the same extent as federal and state laws in the U.S. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the U.S., or from selling or importing products made using our inventions in and into the U.S. or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement rights are not as strong as those in the U.S. These products may compete with our products and our patents or other intellectual property rights may not be effective or adequate to prevent them from competing. In addition, in jurisdictions outside the U.S., a license may not be enforceable unless all the owners of the intellectual property agree or consent to the license. Further, patients may choose to travel to countries in which we do not have intellectual property rights or which do not enforce these rights to obtain the products or treatment from competitors in such countries.

If we or one of our licensing partners initiate legal proceedings against a third party to enforce a patent covering one of our product candidates, the defendant could counterclaim that the patent covering our product candidate is invalid or unenforceable. In patent litigation in the U.S., defendant counterclaims alleging invalidity or unenforceability are commonplace, and there are numerous grounds upon which a third party can assert invalidity or unenforceability of a patent. Third parties may also raise similar claims before administrative bodies in the U.S. or other jurisdictions, even outside the context of litigation. Such mechanisms include re-examination, inter partes review, post-grant review and equivalent proceedings in foreign jurisdictions, such as opposition or derivation proceedings. Such proceedings could result in revocation or amendment to our patents in such a way that they no longer cover and protect our product candidates. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity of our patents, for example, we cannot be certain that there is no invalidating prior art of which we, our patent counsel, and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity, unpatentability and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates. For example, as highlighted in the above risk factor entitled “We could be unsuccessful in obtaining or maintaining adequate patent protection for one or more of our products or product candidates, or asserting and defending our intellectual property rights that protect our products and technologies,” various third parties have filed, and may file in the future, challenges to the validity of patents we own or license (e.g., patents or patent applications in the UC/Vienna/Charpentier patent family). If we or the owners of patents we license (e.g., UC/Vienna/Charpentier) fail in defending the validity of these patents, we (and our sublicensees) may lose the benefit of patents and patent applications we own or license (e.g., patents and patent applications licensed under the Caribou License), as discussed above. Such an outcome could have a material adverse effect on our business in Europe.

In vivo genome editing products and ex vivo engineered cell therapies based on CRISPR/Cas9 genome editing technology are novel, complex and difficult to manufacture.

The manufacturing processes used to produce CRISPR/Cas9-basedCRISPR-based in vivo genome editing product candidates and ex vivo engineered cell therapy product candidates are novel and complex. In addition, our manufacturing processes may require components that are difficult to obtain or manufacture at the necessary quantities and in accordance with regulatory requirements. Several factors could cause production interruptions, including equipment malfunctions; facility unavailability or contamination; raw material cost, shortages or contamination; natural disasters, such as pandemics or other outbreaks or similar public health crises; disruption in utility services; human error; insufficient personnel; inability to meet legal or regulatory requirements; or disruptions in the operations of our suppliers.

Because our product candidates are regulated as biologics, their processing steps will be more complex than those of most small molecule drugs. Moreover, unlike small molecules, the physical and chemical properties of a complex product such as ours generally cannot be fully characterized. As a result, assays of the finished product or relevant components may not be sufficient to ensure that the product will perform in the intended manner. For this reason, we will employ multiple steps to control the manufacturing process to ensure that the process results in product candidates that meet their specifications, but complications at any one step could adversely impact our manufacturing of products. Further, we may encounter problems achieving adequate quantities and quality of clinical (or, if approvedapproved, commercial) grade materials that meet the FDA or other relevant regulatory agency’s applicable standards or our specifications with consistent and acceptable production yields and costs. Manufacturing process irregularities, even minor deviations from the normal process, could result in product defects or manufacturing issues that cause lot failures, product recalls, product liability claims and litigation, insufficient inventory or production interruption. In addition, product manufacturing and supply could be delayed if the FDA and other regulatory authorities require us to submit lot samples, testing results and protocols, or if they require that we not distribute a lot until they authorize the product’s release.

Patient enrollment is a significant factor in the timing of clinical trials and is affected by many factors, including willingness of physicians to use an experimental therapy, the availability of existing treatments, the trial’s geographic locations and the number of patients in each geographic location. In addition, our ability to enroll and dose patients may be delayed by the relevant regulatory authority, as well as the IRB or another ethics committee (whether local or national). For example, as set forth in the National Institutes of Health (“NIH”) Guidelines for Research Involving Recombinant or Synthetic Nucleic Acid Molecules (“NIH Guidelines”), gene therapy clinical trials are also subject to review and oversight by an institutional biosafety committee (“IBC”), a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution. Before a clinical trial can begin at any institution, that institution’s IRB and its IBC assesses the safety of the research and identifies any potential risk to public health or the environment. While the NIH Guidelines are not mandatory unless the research in question is being conducted at or sponsored by institutions receiving NIH funding of recombinant or synthetic nucleic acid molecule research, many companies and other institutions not otherwise subject to the NIH Guidelines voluntarily follow them. Further, a clinical trial may be suspended or terminated by us, the relevant IRBs or ethics committees of the trial, or the FDA or other regulatory authorities, or upon a recommendation of the trial’s DMC, due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a product candidate, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial. For example, in October 2025, the FDA placed a clinical hold on the IND applications for the MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials for patients with ATTR-CM and ATTRv-PN, respectively. The clinical hold on the IND for the MAGNITUDE-2 clinical trial was removed in January 2026, but we cannot predict when we will resolve the clinical hold with the FDA on the IND for the MAGNITUDE clinical trial for nex-z, and there is a risk that we may not be able to resume this trial. For more information, see the above risk factor entitled “We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of any product candidates.” If we experience termination of, or delays in the completion of, any clinical trial of product candidates, the commercial prospects for such product candidates will be harmed, and our ability to generate product revenue will be impaired. In addition, any delays in completing any clinical trials will increase our costs, slow down our product development and approval process and jeopardize our ability to commence product sales and generate revenue.

We are currently conducting our Phase 3 clinical trials of nex-z (pending resolution of the clinical hold on the IND for the MAGNITUDE clinical trial) and NTLA-2002,for lonvo-z, and may in the future conduct clinical trials for our other product candidatescandidates, outside the U.S. The acceptance of data from clinical trials conducted outside the U.S. or another jurisdiction by the FDA or comparable foreign regulatory authority may be subject to certain conditions or may not be accepted at all. The FDA will generally not consider the data from a foreign clinical trial not conducted under an IND unless (i) the trial was well-designed and well-conducted in accordance with good clinical practice (“GCP”) requirements, including requirements for the design, conduct, performance, monitoring, auditing, recording, analysis, and reporting of clinical trials in a way that provides assurance that the data and reported results are credible and accurate and that the rights, safety, and well-being of trial subjects are protected, and (ii) the FDA is able to validate the data from the trial through an onsite inspection, if necessary. Additionally, the FDA’s clinical trial requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory authorities have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the foreign jurisdictions where the trials are conducted. There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the U.S. or the applicable jurisdiction. If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which could be costly and time-consuming, and which may result in product candidates that we may develop not receiving approval for commercialization in the applicable jurisdiction.

We have received orphan drug designation for nex-z and NTLA-2002lonvo-z and may in the future seek orphan drug designation for some of our other product candidates, but we may be unable to obtain such designations or to maintain the benefits associated with orphan drug status, including market exclusivity, which may cause our revenue, if any, to be reduced.

We have received orphan drug designation from the FDA for nex-z for the treatment of ATTR amyloidosisamyloidosis, which is currently the subject of an FDA clinical hold on the IND for the MAGNITUDE clinical trial as described above (see the above risk factor entitled “We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of any product candidates.”), and from the FDA and EC for NTLA-2002lonvo-z for the treatment of HAE. We may seek orphan drug designation for some of our other product candidates in orphan indications in which there is a medically plausible basis for the use of these product candidates. Even where we obtain orphan drug designation, exclusive marketing rights in the U.S. may be limited if we seek approval for an indication broader than the orphan designated indication and may be lost if the FDA later determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantities of the product to meet the needs of patients with the rare disease or condition. In addition, although we intend to seek orphan drug designation for other product candidates, we may never receive such designations.

The FDA may reevaluate the Orphan Drug Act and its regulations and policies. We do not know if, when, or how the FDA may change the orphan drug regulations and policies in the future, and it is uncertain how any changes might affect our business. In addition, proposed amendmentsreforms to EU regulationspharmaceutical regardinglegislation orphanhave medicinesbeen areprovisionally underagreed considerationbetween the Council of the European Union and the European Parliament that, if implemented, could reduce the current 10-year marketingmarket exclusivity period in the EU for certain orphan medicines. Depending on what changes the FDA and the EC may make to their orphan drug regulations and policies, our business could be adversely impacted.

We have received regenerative medicine advanced therapy (“RMAT”) designation by the FDA for nex-z for the treatment of ATTRv-PN and for NTLA-2002lonvo-z for the treatment of HAE, and may in the future seek such designation for some of our other product candidates, but such designation may not actually lead to a faster development or regulatory review or approval process and we may be unable to obtain or maintain the benefits associated with such designation.

We have received the RMAT designation from the FDA for nex-z for the treatment of ATTRv-PNATTRv-PN, which is currently the subject of an FDA clinical hold as described above (see the above risk factor entitled “We may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and NTLA-2002commercialization of any product candidates.”), and for lonvo-z for the treatment of HAE. A product candidate is eligible for RMAT designation if: (1) it is a cell therapy, therapeutic tissue engineering product, human cell or tissue product, or a combination product using any such therapies or products; (2) it is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and (3) there is preliminary clinical evidence that indicates that the product candidate has the potential to address unmet medical needs for such disease or condition. This program is intended to facilitate efficient development and expedite review of RMATs. A BLA for a product candidate with RMAT designation may be eligible for priority review or accelerated approval through (1) surrogate or intermediate endpoints reasonably likely to predict long-term clinical benefit or (2) reliance upon data obtained from a meaningful number of sites. Benefits of such designation also include early interactions with the FDA to discuss any potential surrogate or intermediate endpoint to be used to support accelerated approval. A product candidate that has RMAT designation and is subsequently granted accelerated approval and is subject to post-approval requirements may fulfill such requirements through the submission of clinical evidence, clinical studies, patient registries, or other sources of real-world evidence, such as electronic health records, the collection of larger confirmatory data sets, or post-approval monitoring of all patients treated with such therapy prior to its approval. RMAT designation is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for RMAT designation, the FDA may disagree and instead determine not to grant such designation. In any event, the receipt of RMAT designation for a product candidate may not result in a faster development process, review or approval compared to product candidates considered for approval under conventional FDA procedures and does not assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualifies for RMAT designation, the FDA may later decide that the product candidate no longer meets the conditions for qualification.

Existing regulatory policies mayhave begun to change, and additional government regulations may be enacted that could prevent, limit or delay regulatory approval of our product candidates.

In June 2024, the U.S. Supreme Court overruled the Chevron doctrine, which gave deference to regulatory agencies’ statutory interpretations in litigation against federal government agencies, such as the FDA and Centers for Medicare & Medicaid Services (“CMS”), agencies within the U.S. Department of Health and Human Services,Services (“HHS”), where the law is ambiguous. This decision may result in more lawsuits against the FDA to challenge longstanding decisions and policies of the FDA, which could undermine the FDA’s authority, lead to uncertainties in the industry, and disrupt the FDA’s normal operations, any of which could delay the FDA’s review of our regulatory submissions. We cannot predict the full impact of this decision, future judicial challenges brought against the FDA, or the nature or extent of government regulation that may arise from future legislation or administrative action. In addition, the leadership, personnel, policies, and/or priorities of government departments and agencies responsible for establishing and operating programs and regulations related to pharmaceutical products, such as the U.S. Department of Health and Human Services,HHS, FDA and CMS, maybegan change.to change in 2025. New leadership, personnel, policies, priorities, and/or regulations have affected our industry and may affect our industryproduct and/or products.candidates. For example, FDA or CMS policies and practices concerning gene and cell therapies may change in a way that disparately impacts our product candidates, such as reducing the staff of these agencies or not retaining experienced staff at these agencies who have expertise relevant to our industry and products, and/or products.applying evolving standards for regulatory decisions. If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained, and we may not achieve or sustain profitability.

The Commonwealth of Massachusetts, where most of our employees are based, also has laws that expand on federal laws or create additional rights for employees or obligations for employers. For example, onin July 1, 2018, the Massachusetts Equal Pay Act went into effect, which added protections employers must comply with regarding pay equity for “comparable work.” In addition, onin JulyOctober 31, 2024, Massachusetts passed2025, the Frances Perkins Workplace Equity Act,Act became effective in Massachusetts, requiring disclosure of the pay range for a particular job under certain circumstances, including job postings, promotions, or when an employee requests. There is currently uncertainty regarding the exact scope of these new legal limits and such uncertainty may remain for the foreseeable future. We may face increased employment and legal costs to ensure we are complying with these laws.

The ability of the FDA and other similar regulatory agencies to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel and authorization to accept the payment of user fees, reallocation of resources to address unique or new healthcare issues (or other future public health concerns), and statutory, regulatory, and policy changes. For example, in 2025, the U.S. government issued executive orders and implemented reductions in force that adversely impacted FDA staffing and resources. In addition, government funding of other government agencies on which our operations may rely, including those that fund research and development activities, is subject to the political process, which is inherently fluid and unpredictable. For example, over the last several years, the U.S. government has shut down several times and during such times, certain regulatory agencies, such as the FDA and the SecuritiesSEC, andin Exchangesome Commission (“SEC”),instances have had to furlough critical FDA, SEC and other government employees and stop certain critical activities.

Our technological advancements and any potential for revenue may be derived in part from our collaborations, including, for example, with Regeneron,Regeneron Pharmaceuticals, Inc. (“Regeneron”), and if the collaboration or co-development agreements related to a material collaboration were to be terminated or materially altered in an adverse manner, our business, financial condition, results of operations and prospects would be harmed.

As part of our business strategy, we may pursue acquisitions or licenses of assets or acquisitions of businesses, or disposition of assets or technologies. For example, in February 2022, we announced the acquisition of Rewrite in order to add additional capabilities to our growing platform, which acquisition included an exclusive license from the Regents of the University of California under certain patents related to DNA writing technology. We also may pursue strategic alliances and joint ventures that leverage our core technology and industry experience. If we decide to collaborate with other companies to discover, develop and commercialize therapeutic products, we face significant competition in seeking appropriate collaborators because, for example, third parties have comparable rights to the CRISPR/Cas9 system or similar genome editing technologies. In addition, we have limited experience with acquiring, disposing of or licensing assets or forming strategic alliances and joint ventures. Our ability to reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may have to curtail, delay or abandon discovery efforts or development programs, and the development, manufacture or commercialization of a product candidate, or increase our expenditures and undertake these activities at our own expense. If we elect to fund and undertake discovery, development, manufacturing or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary discovery, development, manufacturing and commercialization activities, we may not be able to further develop our product candidates, manufacture the product candidates, bring them to market or continue to develop our technology and our business may be materially and adversely affected. Furthermore, we may not identify or complete these transactions in a timely manner, on a cost-effective basis, or at all, and we may not realize the anticipated benefits of any acquisition, license, strategic alliance or joint venture.

We are increasingly dependent upon information technology systems, infrastructure, and data to operate our business. In the ordinary course of business, we collect, store, and transmit large amounts of confidential information (including but not limited to intellectual property, such as trade secrets, proprietary business information, and personal information). It is critical that we do so in a secure manner to maintain the confidentiality and integrity of such confidential information. We have also outsourced elements of our operations to third parties, and as a result we manage a number of third party vendors who may or could have access to our confidential information. Our third party collaborators, vendors and service providers (including our CMOs and CROs) also have access to large amounts of confidential information relating to our operations, including our research and development efforts. The size and complexity of our information technology systems, and those of third party vendors, service providers and collaborators, and the large amounts of confidential information stored on those systems, make such systems potentially vulnerable to service interruptions or systems failures, or to cybersecurity incidents, breaches or compromises from inadvertent or intentional actions by our employees, third party vendors, service providers, collaborators, and/or business partners, or from cyber-attackscybersecurity attacks by malicious third parties.

General and administrative expenses consist primarily of compensation and benefits, including stock-based compensation, for our executive, finance, legal, human resources, business development and support functions. Also included in general and administrative expenses are allocated facility-related costs not otherwise included in research and development expenses, adjustments related to impairment or accelerated amortization of long-lived assets, ongoing expenses related to the buildout of our commercial infrastructure, travel expenses and professional fees for auditing, tax and legal services, including IP-related legal services, and other consulting fees and expenses.

Other Income (Expense),Income, Net

DuringOther the year ended December 31, 2024, other income (expense),income, net consists of interest income earned on our cash, cash equivalents, restricted cash equivalents and marketable securities and change in the fair value of our investments. During the year ended December 31, 2023, other income (expense), net consisted of interest income earned on our cash, cash equivalents, restricted cash equivalents and marketable securities, loss from our equity method investment and change in fair value of contingent consideration.

Collaboration revenue increased by $21.6$9.8 million to $67.7 million during the year ended December 31, 2025, as compared to $57.9 million during the year ended December 31, 2024, as compared to $36.3 million during the year ended December 31, 2023.2024. The increase in collaboration revenue during the year ended December 31, 20242025 is primarily due to a $23.7 million increase, primarily in cost reimbursements related to our collaboration with Regeneron Pharmaceuticals, Inc. (“Regeneron”) and $9.0 million in revenue that was recognized as a result of the termination of our License, Collaboration and Option Agreement with SparingVision SAS (the “SparingVision LCA”), offset in part by the recognition of $21.0 million of previously eliminated intra-entity profit under our licenseLicense and collaborationCollaboration agreementAgreement with AvenCell Therapeutics, Inc. (the “AvenCell LCA”) and a $12.8 million increase in revenue related to Regeneron Pharmaceuticals, Inc. (“Regeneron”), offset by a $12.3 million decrease in revenue related to the AvenCellyear LCA.ended December 31, 2024. Refer to NoteNotes 9 and 10 to our consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K for further details.

Research and development expenses increaseddecreased by $31.2$77.5 million to $388.9 million during the year ended December 31, 2025, as compared to $466.3 million during the year ended December 31, 2024, as compared to $435.1 million during the year ended December 31, 2023.2024.

The increasedecrease in research and development expenses for the year ended December 31, 20242025 compared to the year ended December 31, 20232024 was primarily attributable to:

a $15.3$20.7 million increase in external costs related to the development of nexiguran ziclumeran (“nex-z”, also referred to as NTLA-2001), one of our lead product candidates, primarily due to an increase in spend on contracted services and consulting fees, offset in part by a decrease in drug components;

a $17.6$5.6 million increase in external costs related to the development of NTLA-2002,lonvoguran ziclumeran (“lonvo-z”, also referred to as NTLA-2002), one of our lead product candidates, primarily due to an increase in spend on drug components,components and contracted services and consulting fees;

a $6.3$5.0 million increase in facility-related expenses primarily related to depreciation, facility maintenance costs, technologyrent expense allocated to research and development, and rent; and a $12.0$44.8 million increasedecrease in stock-based compensation.compensation caused primarily by our reduced workforce and lower grant date fair values of share-based awards granted in the current period.

General and administrative expenses increaseddecreased by $9.3$6.0 million to $119.8 million during the year ended December 31, 2025, compared to $125.8 million during the year ended December 31, 2024, compared to $116.5 million during the year ended December 31, 2023.2024. This increasedecrease was primarily related to ana increasedecrease in stock-based compensation offset in part by increased expenses related to the ongoing buildout of $8.2our million.commercial infrastructure and reductions to right-of-use assets for accelerated amortization and impairment.

Other Income (Expense),Income, Net

In 2022, we entered into an Open Market Sale Agreement (the “2022 Sale Agreement”) with Jefferies LLC (“Jefferies”), under which Jefferies is able to offer and sell, from time to time in “at-the-market” offerings, shares of our common stock having aggregate gross proceeds of up to $400.0 million. In February 2024, we entered into an amendment to the 2022 Sale Agreement (the “2022 Sale Agreement, as amended”) to increase the size of the at-the-market offering program from $400.0 million to $750.0 million. We agreed to pay cash commissions of up to 3.0% of the gross proceeds of sales of common stock under the 2022 Sale Agreement, as amended. To date through December 31, 20242025 we have issued 14,522,53326,313,157 shares of our common stock under the 2022 Sale Agreement, as amended. During the year ended December 31, 2024,2025, we issued 7,004,37011,790,624 shares of our common stock, in a series of sales, at an average price of $25.68$11.15 per share, in accordance with the 2022 Sale Agreement, as amended, for aggregate net proceeds of $174.8$128.2 million, after payment of cash commissions and approximately $0.3 million related to legal, accounting and other fees in connection with the sales.commissions. As of December 31, 2024,2025, $249.1$117.7 million in shares of common stock remain eligible for sale under the 2022 Sale Agreement, as amended.

Our primary uses of capital are, and we expect will continue to be, research and development research materials and contracted services, clinical trial costs, compensation and related expenses, laboratory and office facilities, research supplies, legal and regulatory expenses, patent prosecution filing and maintenance costs for our licensed IP, commercial launch capabilities, milestone and royalty payments and general overhead costs. During 2025,2026, we expect our research and development expenses to decrease compared to prior periods as a result of our recently announced strategic reorganization in January 2025, as we focus resources on high value programs within our pipeline, such as NTLA-2002lonvo-z and nex-z, to ensure efficient execution, achieve near-term clinical milestones, and prepare for commercial launch. We expect the decrease in research and development expenses to be mostly offset by increased expenses in 2026 related to our ongoing buildout of a commercial infrastructure.

Because our lead programs are in the clinical stage and the outcome of these efforts is uncertain, we cannot estimate the actual amounts necessary to successfully complete the development and commercialization of any future product candidates or whether, or when, we may achieve profitability. Until such time as we can generate substantial product revenues, if ever, we expect to fund our ongoing cash needs through equity financings and collaboration arrangements. We receive cost reimbursements from Regeneron related to our collaboration agreements with them.Regeneron. Additionally, we are eligible to earn milestone payments and royalties, in each case, on a per-product basis under our collaborations with SparingVision SAS (“SparingVision”), ONK Therapeutics, Ltd. (“ONK”) and ReCode Therapeutics, Inc. (“ReCode”), on a per-target basis under our collaboration with Regeneron, androyalties upon achievement of certain events with Kyverna, subject to the provisions ofunder our agreementscollaboration with each of them.agreements. Except for these sources of funding, we will not have any committed external source of liquidity. To the extent that we raise additional capital through the future sale of equity, the ownership interest of our stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing stockholders. If we raise additional funds through collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Based on our research and development plans and our expectations related to the progress of our programs, we expect that our cash, cash equivalents and marketable securities as of December 31, 2024,2025, as well as research and cost reimbursement funding from our collaboration agreements, will enable us to fund our ongoing operating expenses and capital expenditure requirements into the firstsecond half of 2027, excluding any potential milestone payments or extension fees that could be earned and distributed under our collaboration agreements or any strategic use of capital not currently in the base case planning assumptions. We have based this estimate on current assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect.

Our ability to generate revenue and achieve profitability depends significantly on our success in many areas, including: developing our delivery technologies and our CRISPR/Cas9 technology platform; 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 ofand pricing approvals for our product candidates; 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, protecting, and expanding our portfolio of IP rights, including patents, trade secrets, and know-how; and attracting, hiring, and retaining qualified personnel.

Net cash provided by (used in) investing activities

During the year ended December 31, 20232024 we usedadded $125.6 million of net cash of $31.3 million inthrough investing activities. The decreaseincrease in the year ended December 31, 20232024 is primarily due to $17.4$131.3 million in marketable securities purchasedthat matured (net of maturitiespurchases), andoffset $14.0in part by $5.8 million in cash used for the purchase of property and equipment.

Property Leases - Commenced

As of December 31, 2024,2025, our total undiscounted future minimum lease payments for our property leases that have commenced were $294.8$111.2 million, which will be paid over the term of such leases. For additional information on our leases and timing of future payments refer to Note 11, “Leases”, of the consolidated financial statements included in this Annual Report on Form 10-K.

We recognize revenue in accordance with Financial Accounting Standards Board (“FASB”) Accounting Standards Update (“ASU”) 2014-09, Revenue from Contracts with Customers (Topic 606) and its related amendments (collectively known as Accounting Standard Codification (“ASC”) 606 (“ASC 606”)).

As of December 31, 2024,2025, our revenue recognized is solely related to collaboration agreements with third parties which are either within the scope of ASC 606, under which we license certain rights to our product candidates to third parties, or within the scope of ASC 808, Collaborative Arrangements (“ASC 808”) if it involves a joint operating activity pursuant to which we are an active participant and are exposed to significant risks and rewards with respect to the arrangement. As discussed in further detail in Note 9 to our consolidated financial statements of this Annual Report on Form 10-K, we enter into out-licensing agreements which are within the scope of ASC 606, under which we license certain rights to our product candidates to third parties and may provide services related to the research and development of the product candidates. The terms of these arrangements typically include consideration payable to us of one or more of the following: nonrefundable, upfront fees; development, regulatory, and commercial milestone payments; research and development funding payments; and royalties on the net sales of licensed products. Additionally, the terms of certain arrangements may include an equity interest in the other company. Consideration received from each of these payments results in collaboration revenues, except for revenues from royalties on the net sales of licensed products, which are classified as royalty revenues. For arrangements within the scope of ASC 808, the terms of these arrangements typically include payments received or made under the cost sharing provisions which are recognized as a component of collaboration revenues in the consolidated statements of operations and comprehensive loss.

We measure employee stock-based compensation for stock options based on the grant date fair value of the equity awards using the Black-Scholes option pricing model. For awards with service conditions only, we recognize stock-based compensation expense on a straight-line basis over the requisite service period. For equity awards that have a performance or market condition, we recognize stock-based compensation expense using the accelerated attribution method. Estimates of stock-based compensation expense for an award with a performance condition are based on our assessment of the probability that the performance condition will be achieved, which requires significant judgment. Our stock price is a key input thatin will drivedetermining the grant date fair value of the equity awards. Forfeitures are recorded as they occur.

We are not profitable and have incurred losses in each period since our inception. Our net loss was $96.2$202.9 million for the threesix months ended MarchJune 31,30, 2026. As of MarchJune 31,30, 2026, we had an accumulated deficit of $2,686.3$2,793.0 million. We expect these losses to increase as we continue to incur significant research and development and other expenses related to our ongoing operations, seek regulatory approvals for our future product candidates, scale-up manufacturing capabilities, maintain, expand and protect our intellectual property portfolio and hire additional personnel to support the development of our product candidates and to enhance our operational, financial and information management systems. We expect to finance our operations through a combination of collaboration revenue, equity or debt financings or other sources, which may include collaborations with third parties.

The rapid evolution of AI will require the application of significant resources to govern, design, develop, test, maintain and monitor such systems to help ensure that AI is implemented in accordance with applicable law and regulation and in a socially responsible manner and to minimize any real or perceived unintended harmful impacts. The use of certain AI technologies can also give rise to IPintellectual property risks, including by disclosing or otherwise compromising our confidential or proprietary IP,intellectual property, or by undermining our ability to assert or defend ownership rights in IPintellectual property created with the assistance of AI tools.

Our vendors may in turn incorporate AI tools into their offerings, and the providers of these AI tools may not meet existing or rapidly evolving regulatory or industry standards, including with respect to privacy and data security. Further, bad actors around the world use increasingly sophisticated methods, including the use of AI, to engage in illegal activities involving the theft and misuse of personal information, confidential information and IP.intellectual property. Any of these effects could damage our reputation, result in the loss of valuable property and information, cause us to breach applicable laws and regulations, and adversely impact our business.

The biotechnology and pharmaceutical industries are extremely competitive in the race to develop new products. While we believe we have significant competitive advantages with our industry-leading expertise in genome editing, clinical development expertise and dominant IPintellectual property position, we currently face and will continue to face competition for our development programs from companies that use genome editing or gene therapy development platforms and from companies focused on more traditional therapeutic modalities such as small molecules and antibodies. The competition is likely to come from multiple sources, including large and specialty pharmaceutical and biotechnology companies, academic research institutions, government agencies and public and private research institutions. Many of these competitors may have access to greater capital and resources than us. For any products that we may ultimately commercialize, not only will we compete with any existing therapies and those therapies currently in development, but we will also have to compete with new therapies that may become available in the future.

Third party payors, whether domestic or foreign, or governmental or commercial, are developing increasingly sophisticated methods of controlling healthcare costs. In the U.S. and certain other jurisdictions, there have been, and are expected to continue to be, a number of legislative and regulatory changes to the healthcare system that could impact our ability to sell our products profitably. In addition, significant uncertainty exists in the U.S. and certain other jurisdictions regarding the provision and financing of healthcare because the elected administrations in such countries have publicly declared their intention to review and potentially significantly modify the current legal and regulatory framework for the healthcare system. For example, recent CMS proposals, including the GLOBE,Global GUARD,Benchmark for Efficient Drug Pricing (“GLOBE”), the Guarding U.S. Medicare Against Rising Drug Costs (“GUARD”), and GENEROUS,the GENErating cost Reductions fOr U.S. Medicaid (“GENEROUS”) models, which seek to incorporate most-favored-nation (“MFN”) drug pricing into Medicare and Medicaid, could materially impact our revenue.

Our management has broad discretion to use our cash, cash equivalents and marketable securities to fund our operations and could spend these funds in ways that do not improve our results of operations or enhance the value of our common stock. The failure by our management to apply these funds effectively could result in financial losses that could have a material adverse effect on our business, cause the price of our common stock to decline and delay the development of our product candidates. Pending our use to fund operations, we may invest our cash, cash equivalents and marketable securities in a manner that does not produce income or that loses value.

our ability to execute our planned commercial launch of lonvoguran ziclumeran (“lonvo-z,” previously referred to as NTLA-2002), our program for the treatment of hereditary angioedema (“HAE”), including the ability to successfully completethat the filingU.S. Food and Drug Administration (“FDA”) will accept our submission of a biologics license application (“BLA”) orseeking comparable marketing applicationapproval for lonvo-z in the second half of 2026, we expect to receive approval to market lonvo-z, and we plan to launch lonvo-z in the U.S. in the first half of 2027, or the success of such program;

our ability to execute our clinical study strategy for nexiguran ziclumeran (“nex-z,” previously referred to as NTLA-2001), our program for the treatment of transthyretin (“ATTR”) amyloidosis, including the ability to resume dosing in the MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials following removal of the clinical hold placed by the U.S. Food and Drug Administration (“FDA”) on their Investigational New Drug (“IND”) applications, theour ability to complete enrollment in MAGNITUDE-2 in the second half of 2026, and theour ability to successfully complete thisthe study,MAGNITUDE and MAGNITUDE-2 Phase 3 studies, or the success of such program;

For over a decade, we have applied our proprietary technologies and expertise, including CRISPR-based gene editing technologies, oligonucleotides, and lipid nanoparticles (“LNPs”), to develop novel, first-in-class product candidates. This includes the development of lonvoguran ziclumeran (“lonvo-z,” previously referred to as NTLA-2002) for the treatment of hereditary angioedema (“HAE”) and nexiguran ziclumeran (“nex-z,” previously referred to as NTLA-2001) for the treatment of transthyretin (“ATTR”) amyloidosis. These lead product candidates are the first in vivo genome editing product candidates to advance into Phase 3 clinical development. These systemically administered CRISPR-based candidates are designed to address diseases with high unmet need with a single intravenous (“IV”) infusion that is administered in an outpatient setting. In April 2026, we reported positive topline data from the global Phase 3 HAELO clinical trial of lonvo-z in HAE, and preparations are underway for the planned commercial launch of lonvo-z in the first half of 2027.2027, if approved.

Our strategy is to (1) advance the clinical development of our lead CRISPR-based product candidates, (2) build and leverage a fully integrated commercial-stage infrastructure, (3) expand our pipeline utilizing our expertise and proprietary technologies, and (4) collaborate with partners to expand our technology reach and maximize our return on investment. All of our revenue to date has been collaboration revenue. Since our inception and through MarchJune 31,30, 2026, we have funded our operations through our initial public offering (“IPO”), private placements, follow-on public offerings, at-the-market offerings, the sale of convertible preferred stock and through our collaboration agreements.

In April 2026, we announced positive topline results from the global Phase 3 HAELO clinical trial. In June 2026, we reported additional data in a late-breaking oral session at the European Academy of Allergy & Clinical Immunology Annual Congress 2026 and in a manuscript published in the New England Journal of Medicine. The trial met its primary endpoint. For the six-month efficacy evaluation period (weeks 5 to 28), a one-time infusion of lonvo-z reduced attacks by 87% versus placebo, with a mean monthly attack rate of 0.26 in the lonvo-z arm compared with 2.10 in the placebo arm (p<0.0001). The trial met all of its key secondary endpoints with statistical significance (p<0.0001). These included a: 62% rate of patients who were entirely attack free and therapy free in the lonvo-z arm for the six-month efficacy evaluation period, compared with 11% of patients in the placebo arm; the mean monthly rate of attacks requiring on-demand treatment was 0.19 in the lonvo-z arm for the six-month efficacy evaluation period, compared with 1.79 in the placebo arm; the mean monthly rate of moderate/severe attacks was 0.11 in the lonvo-z arm for the six-month efficacy evaluation period, compared with 1.23 in the placebo arm; and the change in Angioedema Quality of Life (“AE-QoL”) total score was -23.51 in the lonvo-z arm from baseline to Week 28, compared with -6.47 in the placebo arm. Additionally, all patients in the lonvo-z arm experienced attack-rate reductions from baseline compared with weeks 5 to 28; attack-rate reductions were observed for all evaluated subgroups; and all patients who received lonvo-z at baseline or in crossover after week 28 remained free from long-term prophylaxis therapy as of the February 10, 2026 data cutoff. Favorable safety and tolerability data were observed for lonvo-z. The most common treatment emergent adverse events (“TEAEs”) during the primary observation period (infusion through week 28) were infusion-related reactions, headacheheadache, fatigue, back pain, and fatigue.upper respiratory tract infection. All TEAEs reported as of the data cutoff (February 10, 2026) were mild or moderate (Grade 1 or Grade 2) and there were no serious adverse events observed in the lonvo-z arm. As of the data cutoff, all patients who received lonvo-z at baseline or in crossover after week 28 remained free from long-term prophylaxis therapies.

We significantly advanced our launch readiness activities in recent months, including finalizing our field medical, reimbursement and strategic accounts teams and engaging with HAE treatment centers around the U.S. In April 2026, we announced the initiation of a rolling biologics license application (“BLA”) to the U.S. Food and Drug Administration (“FDA”) to seek regulatory approval for lonvo-z. We expect the FDA to completeaccept our BLA submission to the FDA in the second half of 20262026. If approved, we plan to support a potential U.S. launch oflonvo-z lonvo-zcommercially in the first half of 2027.

On October 29, 2025, the FDA placed a clinical hold on the investigational new drug (“IND”) applications for the MAGNITUDE and MAGNITUDE-2 Phase 3 clinical trials for patients with ATTR amyloidosis with cardiomyopathy (“ATTR-CM”) and hereditary ATTR with polyneuropathy (“ATTRv-PN’),ATTRv-PN, respectively. This action followed a report of Grade 4 liver transaminase elevations and increased total bilirubin in a patient who was dosed with nex-z in the MAGNITUDE trial. This patient passed away on November 5, 2025. It was reported by the principal investigator that the patient died due to septic shock secondary to a perforated duodenal ulcer. The patient’s complicated clinical course also included acute liver injury and its treatment with corticosteroids. An autopsy report supported the clinical diagnoses.

In January 2026, we announced that the FDA lifted the clinical hold on the IND for MAGNITUDE-2 for patients with ATTRv-PN. In March 2026, we announced that the FDA lifted the clinical hold on the IND for MAGNITUDE for patients with ATTR-CM. Patient screeningenrollment activities areis advancing in both trials.

Nex-z is the subject of a co-development and co-promotion (“Co/Co”) agreement (the “ATTR Co/Co”) with Regeneron Pharmaceuticals, Inc. (“Regeneron”),Regeneron, for which we are the clinical and commercial lead party and Regeneron is the participating party. Regeneron shares in approximately 25% of worldwide development costs and commercial profits for the ATTR program and has an option to enter into a co-promotion agreement for the U.S. commercialization.

In November 2024, we announced that the FDA had cleared our nex-z Investigational New Drug (“IND”) application to initiate the MAGNITUDE-2 pivotal Phase 3 trial for ATTRv-PN. MAGNITUDE-2 is an international, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of nex-z in 50 adults with ATTRv-PN. Patients will be randomized 1:1 to receive a single 55 mg infusion of nex-z or placebo. Patients randomized to the placebo arm will be eligible for optional crossover to receive nex-z following month 18. The primary endpoints are the change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at month 18 and serum TTR at day 29. The mNIS+7 scale is a validated measure specifically designed to assess and quantify polyneuropathy impairment, including muscle weakness, muscle stretch reflexes, sensory loss and autonomic impairment. In April 2025, we announced that the first patient was randomized and dosed with nex-z in the global Phase 3 MAGNITUDE-2 study.

We planremain on track to complete patient enrollment in MAGNITUDE-2 in the second half of 2026.

In order to treat—and potentially cure—a broader range of severe diseases, we and our collaboration partners are advancing the development of additional clinical and preclinical product candidates. Throughout our history, we have leveraged collaborations to expand and accelerate the development of product candidates. Our current relationships include our collaboration with Regeneron Pharmaceuticals, Inc. (“Regeneron”) and other research collaborations focused on the development of product candidates. See Note 7, “Collaborations and Other Arrangements” of our condensed consolidated financial statements appearing elsewhere in this Quarterly Report on Form 10-Q for additional information related to the terms of the agreements between us and our collaborators.

General and administrative expenses consist primarily of compensation and benefits, including stock-based compensation, for our executive, finance, legal, human resources, business development and support functions. Also included in general and administrative expenses are allocated facility-related costs not otherwise included in research and development expenses, adjustments related to impairment or accelerated amortization of long-lived assets, ongoing expenses related to the buildout of our commercial infrastructure, travel expenses and professional fees for auditing, tax and legal services, including IP-relatedintellectual property-related legal services, and other consulting fees and expenses.

During the three and six months ended MarchJune 31,30, 2026 and 2025, other income (expense), net consists of interest income earned on our cash, cash equivalents, restricted cash equivalents and marketable securities and change in the fair value of our investments.

Comparison of Three Months Ended MarchJune 31,30, 2026 and 2025

Collaboration revenue decreased by $1.6$6.6 million during the three months ended MarchJune 31,30, 2026, as compared to the three months ended MarchJune 31,30, 2025. The decrease in collaboration revenue is primarily due to a reductionreductions in revenue under the license and collaboration agreement with AvenCell Therapeutics, Inc. (the “AvenCell LCA”), as well as the achievement of a development milestone under the 2016 Regeneron Agreement in March of 2025, partially offset by an increase in revenue related toand the ATTR Co/Co.

Research and development expenses decreased by $27.7$14.4 million during the three months ended MarchJune 31,30, 2026, as compared to the three months ended MarchJune 31,30, 2025.

The decrease in research and development expenses for the three months ended MarchJune 31,30, 2026 compared to the three months ended MarchJune 31,30, 2025 was primarily attributable to:

a $2.9$5.7 million decrease in external costs related to the development of nex-z, one of our lead product candidates, primarily due to a decrease in spend on contracted services and drugconsulting componentsfees;

a $2.5 million decrease in external costs related to the development of lonvo-z, one of our lead product candidates, primarily due to a decrease in spend on drug components and contracted services, offset in part by an increase in consulting fees;

a $7.0$1.9 million decreaseincrease in employee-related expenses driven primarily by decreasedincreased employee headcount in 2026, offset in part by a decrease in consulting costs and severance expense related to the Company's workforce reduction in January 2025fees;

a $7.6$3.0 million decrease in research materials and contracted services driven primarily driven by a decrease in internalspend research and development spend, contracted services andon drug components;

a $2.4$0.9 million decrease in facility-related expenses primarily related to a decrease in rent expense allocated to research and development; and a $5.0$4.6 million decrease in stock-based compensation driven by lower grant date fair values of share-based awards granted in the current period.

General and administrative expenses increased by $5.8$10.6 million during the three months ended MarchJune 31,30, 2026, as compared to the three months ended MarchJune 31,30, 2025. This increase is primarily related to increased legal expensesexpenses, compensation, and consulting costs associated with the Company’s continued buildout of thea commercial function, partially offset by a decrease in stock-based compensation.function.

The decrease in other income, net of $2.2$2.6 million is primarily related to a $3.4$1.6 million decrease in interest income,income partially offset byand a $1.2$1.0 million decrease in expenseincome due to the change in fair value of our investment.

Since our inception through MarchJune 31,30, 2026, we have funded our operations through an initial public offering, private placements, follow-on public offerings, at-the-market offerings, the sale of convertible preferred stock and through our collaboration agreements.

As of MarchJune 31,30, 2026, we had $517.2$628.4 million in cash, cash equivalents and marketable securities.

In March 2022, we entered into an Open Market Sale Agreement (the “2022 Sale Agreement”) with Jefferies LLC (“Jefferies”), under which Jefferies was able to offer and sell, from time to time in “at-the-market” offerings, shares of our common stock having aggregate gross proceeds of up to $400.0 million. In February 2024, we entered into an amendment to the 2022 Sale Agreement to increase the size of the at-the-market offering program from $400.0 million to $750.0 million. In March 2026, we entered into Amendment No. 2 to the 2022 Sale Agreement (the “2022 Sale Agreement, as amended”) to increase the size of the at-the-market offering program from $750.0 million to $1,035.3 million. We agreed to pay cash commissions of up to 3.0% of the gross proceeds of sales of common stock under the 2022 Sale Agreement, as amended. Through MarchJune 31,30, 2026 we have issued 28,925,501 shares of our common stock under the 2022 Sale Agreement, as amended. During the threesix months ended MarchJune 31,30, 2026, we issued 2,612,344 shares of our common stock, in a series of sales, at an average price of $13.21 per share, in accordance with the 2022 Sale Agreement, as amended, for aggregate net proceeds of $33.6 million, after commissions and offering costs. As of MarchJune 31,30, 2026, $368.5 million in shares of common stock remain eligible for sale under the 2022 Sale Agreement, as amended.

Our primary uses of capital are, and we expect will continue to be, research and development research materials and contracted services, clinical trial costs, compensation and related expenses, laboratory and office facilities, research supplies, legal and regulatory expenses, patent prosecution filing and maintenance costs for our licensed IP,intellectual property, commercial launch capabilities, milestone and royalty payments and general overhead costs. During 2026, we expect our research and development expenses to decrease compared to prior periods as we focus resources on high value programs within our pipeline, such as lonvo-z and nex-z, to ensure efficient execution, achieve near-term clinical milestones, and prepare for commercial launch. We expect the decrease in research and development expenses to be mostly offset by increased expenses in 2026 related to our ongoing buildout of a commercial infrastructure.

Based on our research and development plans and our expectations related to the progress of our programs, we expect that our cash, cash equivalents and marketable securities as of MarchJune 31,30, 2026, the net proceeds from our April 2026 equity offering, as well as research and cost reimbursement funding from our collaboration agreements, will enable us to fund our ongoing operating expenses and capital expenditure requirements at least into 2028, excluding any potential milestone payments or extension fees that could be earned and distributed under our collaboration agreements oragreements, any strategic use of capital not currently in the base case planning assumptions.assumptions and any potential commercial revenues from lonvo-z. We have based this estimate on current assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect.

Our ability to generate revenue and achieve profitability depends significantly on our success in many areas, including: developing our delivery technologies and our CRISPR/Cas9 technology platform; 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 and pricing approvals for our product candidates; 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, protecting, and expanding our portfolio of IPintellectual property rights, including patents, trade secrets, and know-how; and attracting, hiring, and retaining qualified personnel.

Net cash used in operating activities of $117.3$200.5 million during the threesix months ended MarchJune 31,30, 2026 primarily consists of a net loss of $96.2$202.9 million, accretion of investment discounts of $0.5$1.1 million and net changes in operating assets and liabilities of $37.2$33.0 million, partially offset by stock-based compensation of $13.5$31.6 million, depreciation expense of $2.2$4.3 million and a change in fair value of our investment in Kyverna Therapeutics, Inc. (“Kyverna”) of $0.9$0.6 million.

Net cash used in operating activities of $148.9$248.6 million during the threesix months ended MarchJune 31,30, 2025 primarily consists of a net loss of $114.3$215.6 million, further reduced by accretion of investment discounts of $2.3$3.9 million and net changes in operating assets and liabilities of $58.8 million, partially offset by decreases in stock-based compensation of $21.8 million, depreciation expense of $2.5 million and a change in fair value of our investment in Kyverna of $2.1$78.7 million. Included in the net cash used in operating activities wasis approximately $51.0$65.0 million of non-recurring cash payments associated with aour previously announced portfolio prioritization, workforce reduction, and real estate consolidation. These decreases are offset in part by stock-based compensation of $43.9 million, $0.8 million in net adjustments to the fair value of our investment in Kyverna and depreciation expense of $5.0 million.

Net cash (used in) provided by investing activities

During the threesix months ended MarchJune 31,30, 2026, our investing activities providedused cash of $66.3$75.3 million. The increasedecrease in the threesix months ended MarchJune 31,30, 2026 is primarily due to $66.4$73.5 million in maturitiespurchases of marketable securities (net of maturities) and $1.9 million for purchases). of property and equipment.

During the threesix months ended MarchJune 31,30, 2025 our investing activities provided cash of $94.3$201.2 million. The increase is primarily due to $95.1$202.2 million of marketable securities maturing (net of purchases), partially offset by $0.7$1.0 million in cash for the purchase of property and equipment.

Net cash provided by financing activities of $33.6$229.7 million during the threesix months ended MarchJune 31,30, 2026 is primarily related to $194.6 million in net proceeds from a follow-on public offering and $33.6 million in net proceeds from at-the-market offerings. There was no cash provided by financing activities during the three months ended March 31, 2025.

There were no material changes to our contractual obligations during the threesix months ended MarchJune 31,30, 2026 other than those described within Note 9, “Leases” in the notes to condensed consolidated financial statements. For a complete discussion of our contractual obligations, please refer to our Management’s Discussion and Analysis of Financial Condition and Results of Operations in our Annual Report for the year ended December 31, 2025.