10q10k10q10k.net

What changed in CRISPR Therapeutics AG's 10-K — 2024 vs 2025

vs

Paragraph-level year-over-year comparison of CRISPR Therapeutics AG's 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+739 added−648 removedSource: 10-K (2026-02-12) vs 10-K (2025-02-11)

Top changes in CRISPR Therapeutics AG's 2025 10-K

739 paragraphs added · 648 removed · 485 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

193 edited+162 added−82 removed330 unchanged
Biggest changeOther Partnerships We have entered into a number of additional collaborations and license agreements in other therapeutic areas, including an additional agreement with Vertex for the treatment of Duchenne muscular dystrophy, or DMD, and myotonic dystrophy type 1, or DM1, and others to support and complement our hematopoietic stem cell, CAR T, in vivo and T1D programs and platform, including agreements with: Nkarta, Inc., or Nkarta, to develop and commercialize products leveraging donor-derived, gene-edited CAR-NK cells; Capsida Biotherapeutics, Inc. to develop in vivo gene editing therapies delivered with engineered adeno-associated virus, or AAV, vectors; Roswell Park Comprehensive Cancer Center to advance a gene-edited autologous CAR T program against a new target; MaxCyte, Inc. on ex vivo delivery for our hemoglobinopathy and CAR T programs; CureVac AG on optimized mRNA constructs and manufacturing for certain in vivo programs; and KSQ Therapeutics, Inc. on intellectual property for our allogeneic immuno-oncology programs.
Biggest changeWe have entered into a number of additional collaborations, research and license agreements in other therapeutic areas, including an additional agreements with Vertex including for the treatment of Duchenne muscular dystrophy, or DMD, and myotonic dystrophy type 1, or DM1, as well as diabetes, and others, including to support and complement our hematopoietic stem cell, CAR T, in vivo and diabetes programs and platform.
We believe that our innovative research, translational expertise, and clinical development experience, position us as a leader in the development of CRISPR-based therapeutics and may enable us to create an entirely new class of highly effective and potentially curative therapies for patients with both rare and common diseases for whom current biopharmaceutical approaches have had limited success.
We believe that our innovative research, translational expertise, and clinical development experience, position us as a leader in the development of CRISPR-based therapeutics and may enable us to create an entirely new class of highly effective and potentially curative therapies for patients with both common and rare diseases for whom current biopharmaceutical approaches have had limited success.
Caribou Biosciences, or Caribou, has reported that it had an exclusive license to patent rights from California and Vienna, subject to a retained right to allow non-profit entities to use the inventions for research and educational purposes. Intellia Therapeutics, Inc., or Intellia Therapeutics, has reported that it had an exclusive license to such rights from Caribou in certain fields.
Caribou Biosciences, or Caribou, has reported that it had an exclusive license to patent rights from California and Vienna, subject to a retained right to allow non-profit entities to use the inventions for research and educational purposes. Intellia Therapeutics, Inc., or Intellia, has reported that it had an exclusive license to such rights from Caribou in certain fields.
In addition, we believe our facility has the capacity and necessary technology to support additional programs we may advance in the future, including some of our in vivo programs as well as our T1D program, as well as the production of various critical components, such as mRNA, we may utilize in the future.
In addition, we believe our facility has the capacity and necessary technology to support additional programs we may advance in the future, including some of our in vivo programs and our T1D program, as well as the production of various critical components, such as mRNA, we may utilize in the future.
In addition to competition from other gene editing therapies or gene or cell therapies, any product we may develop may also face competition from other types of therapies, such as small molecule, antibody or protein therapies. In addition, new scientific discoveries may cause CRISPR/Cas9 technology, or gene editing as a whole, to be considered an inferior form of therapy.
In addition to competition from other gene editing therapies or gene or cell therapies, any product we may develop may also face competition from other types of therapies, such as small molecule, antibody or protein therapies. New scientific discoveries may also cause CRISPR/Cas9 technology, or gene editing as a whole, to be considered an inferior form of therapy.
Eligible products must target conditions for which there is an unmet medical need (meaning there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicine will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods or therapy or improving existing ones.
Eligible products must target conditions for which there is an unmet medical need (meaning there is no satisfactory method of diagnosis, prevention or treatment in the EU or, if there is, the new medicine will bring a major therapeutic advantage) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.
False Claims Act; • the federal false statements statute prohibits knowingly and willfully falsifying, concealing, or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items, or services; similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation; • the anti-inducement law, which prohibits, among other things, the offering or giving of remuneration, which includes, without limitation, any transfer of items or services for free or for less than fair market value (with limited exceptions), to a Medicare or Medicaid beneficiary that the person knows or should know is likely to influence the beneficiary’s selection of a particular supplier of items or services reimbursable by a federal or state governmental program; • the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, collectively HIPAA, which imposes criminal and civil liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program (including private payors) or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services; • HIPAA, which impose obligations with respect to safeguarding the privacy, security, and transmission of individually identifiable information that constitutes protected health information, including mandatory contractual terms and restrictions on the use and/or disclosure of such information without proper authorization; • the federal transparency requirements known as the federal U.S.
False Claims Act; • the federal false statements statute prohibits knowingly and willfully falsifying, concealing, or covering up a material fact or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items, or services; similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific 38 intent to violate it in order to have committed a violation; • the anti-inducement law, which prohibits, among other things, the offering or giving of remuneration, which includes, without limitation, any transfer of items or services for free or for less than fair market value (with limited exceptions), to a Medicare or Medicaid beneficiary that the person knows or should know is likely to influence the beneficiary’s selection of a particular supplier of items or services reimbursable by a federal or state governmental program; • the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, or HITECH, and their respective implementing regulations, collectively HIPAA, which imposes criminal and civil liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program (including private payors) or obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly and willfully falsifying, concealing or covering up by any trick or device a material fact or making any materially false statements in connection with the delivery of, or payment for, healthcare benefits, items or services; • HIPAA, which impose obligations with respect to safeguarding the privacy, security, and transmission of individually identifiable information that constitutes protected health information, including mandatory contractual terms and restrictions on the use and/or disclosure of such information without proper authorization; • the federal transparency requirements known as the federal U.S.
Department of Health and Human Services, or HHS, information related to payments and other transfers of value made by that entity to physicians (currently defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician providers such as physician assistants and nurse practitioners, and teaching hospitals, and requires certain manufacturers and applicable group purchasing organizations to report ownership and investment interests held by physicians or their immediate family members; • federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • The Foreign Corrupt Practices Act prohibits companies and their intermediaries from making, or offering or promising to make 37 improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; and • analogous laws and regulations in other national jurisdictions and states, such as state anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.
Department of Health and Human Services, or HHS, information related to payments and other transfers of value made by that entity to physicians (currently defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician providers such as physician assistants and nurse practitioners, and teaching hospitals, and requires certain manufacturers and applicable group purchasing organizations to report ownership and investment interests held by physicians or their immediate family members; • federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs; • federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers; • The Foreign Corrupt Practices Act prohibits companies and their intermediaries from making, or offering or promising to make improper payments to non-U.S. officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment; and • analogous laws and regulations in other national jurisdictions and states, such as state anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.
An applicant seeking approval to market and distribute a new biologic in the United States generally must satisfactorily complete each of the following steps: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practice, or GLP, regulations; • submission to the FDA of an Investigational New Drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated, or by a central IRB if appropriate; • performance of adequate and well-controlled human clinical trials to establish the safety, potency, and purity of the product candidate for each proposed indication, in accordance with the FDA’s Good Clinical Practice, or GCP, regulations; • preparation and submission to the FDA of a Biologics License Application, or BLA, for a biologic product requesting marketing for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product and proposed labeling; • review of the product by an FDA advisory committee, where appropriate or if applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with cGMP requirements and to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, strength, quality, and purity, and, if applicable, the FDA’s current good tissue practice, or CGTP, for the use of human cellular and tissue products; • satisfactory completion of any FDA audits of the nonclinical study and clinical trial sites to assure compliance with GLPs and 24 GCPs, respectively, and the integrity of clinical data in support of the BLA; • payment of user fees and securing FDA approval of the BLA; and • compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and Mitigation Strategy, or REMS, adverse event reporting, and compliance with any post-approval studies required by the FDA.
An applicant seeking approval to market and distribute a new biologic in the United States generally must satisfactorily complete each of the following steps: • preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the FDA’s Good Laboratory Practice, or GLP, regulations; • submission to the FDA of an Investigational New Drug, or IND, application for human clinical testing, which must become effective before human clinical trials may begin; • approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated, or by a central IRB if appropriate; • performance of adequate and well-controlled human clinical trials to establish the safety, potency, and purity of the product candidate for each proposed indication, in accordance with the FDA’s Good Clinical Practice, or GCP, regulations; • preparation and submission to the FDA of a Biologics License Application, or BLA, for a biologic product requesting marketing for one or more proposed indications, including submission of detailed information on the manufacture and composition of the product and proposed labeling; • review of the product by an FDA advisory committee, where appropriate or if applicable; • satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities, including those of third parties, at which the product, or components thereof, are produced to assess compliance with cGMP requirements and to assure that the facilities, methods, and controls are adequate to preserve the product’s identity, strength, quality, and purity, and, if applicable, the FDA’s current good tissue practice, or CGTP, for the use of human cellular and tissue products; • satisfactory completion of any FDA audits of the nonclinical study and clinical trial sites to assure compliance with GLPs and GCPs, respectively, and the integrity of clinical data in support of the BLA; • payment of user fees and securing FDA approval of the BLA; and • compliance with any post-approval requirements, including the potential requirement to implement a Risk Evaluation and 25 Mitigation Strategy, or REMS, adverse event reporting, and compliance with any post-approval studies required by the FDA.
Other potential 29 consequences of a failure to comply with regulatory requirements include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, untitled or warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
Other potential consequences of a failure to comply with regulatory requirements include, among other things: • restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls; • fines, untitled or warning letters or holds on post-approval clinical trials; • refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product license approvals; • product seizure or detention, or refusal to permit the import or export of products; or • injunctions or the imposition of civil or criminal penalties.
Individual states in the United States have also become 39 increasingly active in enacting legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
Individual states in the United States have also become increasingly active in enacting legislation and implementing regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
The primary intent of the CGTP requirements is to ensure that cell and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission, and spread of communicable disease. FDA regulations also require tissue establishments to register and list their HCT/Ps with the FDA and, when applicable, to evaluate donors through screening and testing.
The primary intent of the CGTP requirements is to ensure that 27 cell and tissue-based products are manufactured in a manner designed to prevent the introduction, transmission, and spread of communicable disease. FDA regulations also require tissue establishments to register and list their HCT/Ps with the FDA and, when applicable, to evaluate donors through screening and testing.
Even if a product is considered to be an innovative medicinal product so that the innovator gains the prescribed period of data exclusivity, another company nevertheless could also market another version of the product if such company obtained a marketing authorization based on an MAA with a complete independent data package of pharmaceutical tests, preclinical tests and clinical trials.
Even if a product is considered to be an innovative medicinal product so 34 that the innovator gains the prescribed period of data exclusivity, another company nevertheless could also market another version of the product if such company obtained a marketing authorization based on an MAA with a complete independent data package of pharmaceutical tests, preclinical tests and clinical trials.
Item 1. Business. BUSINESS Overview Our mission is to create transformative gene-based medicines for serious human diseases. We are a leading gene editing company focused on the development of CRISPR-based therapeutics, including by using CRISPR/Cas9 technology. CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA.
Item 1. Business. BUSINESS Overview Our mission is to create transformative gene-based medicines for serious human diseases. We are a leading biopharmaceutical company focused on the development of CRISPR-based therapeutics, including by using CRISPR/Cas9 technology. CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA.
If a single cut is made, a process called non-homologous end joining can result in the addition or deletion of base pairs, disrupting the original DNA sequence and causing gene inactivation. A larger fragment of DNA can also be deleted by using two gRNAs that target separate sites.
If a single cut is made, a 3 process called non-homologous end joining can result in the addition or deletion of base pairs, disrupting the original DNA sequence and causing gene inactivation. A larger fragment of DNA can also be deleted by using two gRNAs that target separate sites.
Additionally, technologies developed by our competitors may render our potential product candidates uneconomical or obsolete, and we may not be successful in marketing any product candidates we may develop against competitors. The key competitive factors affecting the success of all of our programs are likely to be their efficacy, safety, convenience, and availability of 23 reimbursement.
Additionally, technologies developed by our competitors may render our potential product candidates uneconomical or obsolete, and we may not be successful in marketing any product candidates we may develop against competitors. The key competitive factors affecting the success of all of our programs are likely to be their efficacy, safety, convenience, and availability of reimbursement.
Under the centralized procedure in the EU, the maximum timeframe for the evaluation of an MAA by the EMA is 210 days from receipt of a valid MAA, excluding clock stops when additional information or written or oral explanation is to be provided by the applicant in response to questions of the CHMP.
Under the centralized procedure in the EU, the maximum timeframe for the evaluation of an MAA by the EMA is 210 days from receipt of a valid MAA, excluding clock stops when additional information or written or oral explanation is to be 33 provided by the applicant in response to questions of the CHMP.
Charpentier and her collaborators elucidated this mechanism and developed ways to adapt and simplify it for use in gene editing. In recognition of this groundbreaking work, Dr. Charpentier was awarded the 2020 Nobel Prize in Chemistry along with her collaborator, Dr. Jennifer Doudna of the University of California, Berkeley.
Emmanuelle Charpentier and her collaborators elucidated this mechanism and developed ways to adapt and simplify it for use in gene editing. In recognition of this groundbreaking work, Dr. Charpentier was awarded the 2020 Nobel Prize in Chemistry along with her collaborator, Dr. Jennifer Doudna of the University of California, Berkeley.
In addition, many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.
Many of our current or potential competitors, either alone or with their collaboration partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.
If our current programs are approved for the indications for which we are currently planning clinical trials, they may compete with other products currently under development, including gene editing, gene therapy, and cell therapy products. Competition with other related products currently under development may include competition for clinical trial sites, patient recruitment, and product sales.
If our current programs are approved for the indications for which we are currently planning clinical trials, they may compete with other products currently under development, including gene editing, gene therapy, and cell therapy products. Competition with 24 other related products currently under development may include competition for clinical trial sites, patient recruitment, and product sales.
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.
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 26 otherwise subject to the NIH Guidelines voluntarily follow them.
CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of CASGEVY as a potential one-time functional cure for people with severe SCD and TDT.
Overall, CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of CASGEVY as a potential one-time functional cure for people with severe SCD and TDT.
Since October 2015, we have entered into a Strategic Collaboration, Option and License Agreement, as amended in 2017 and 2019, or the 2015 Collaboration Agreement; a Joint Development and Commercialization Agreement, or the Vertex JDA, which was amended and restated in April 2021, or the A&R Vertex JDCA, as amended in December 2023, or the Amended A&R Vertex JDCA; and a Strategic Collaboration and License Agreement, as amended in April 2021, or the 2019 Collaboration Agreement.
Since October 16 2015, we have entered into a Strategic Collaboration, Option and License Agreement, as amended in 2017 and 2019, or the 2015 Collaboration Agreement; a Joint Development and Commercialization Agreement, or the Vertex JDA, which was amended and restated in April 2021, or the A&R Vertex JDCA, as amended in December 2023, or the Amended A&R Vertex JDCA.
Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes evaluation and assessment by an IBC, a local institutional committee that reviews and oversees research 25 utilizing recombinant or synthetic nucleic acid molecules at that institution.
Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes evaluation and assessment by an IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution.
If so designated, the FDA may expedite the development and review of any subsequent original BLA for a drug that uses or incorporates the platform technology. Designated platform technology status does not 28 ensure that a drug will be developed more quickly or receive FDA approval.
If so designated, the FDA may expedite the development and review of any subsequent original BLA for a drug that uses or incorporates the platform technology. Designated platform technology status does not ensure that a drug will be developed more quickly or receive FDA approval.
At the appropriate time in the product development process, we will determine whether to utilize our own manufacturing facility or continue to rely on third parties to manufacture commercial quantities of any products that we may successfully develop.
At the appropriate time in the product development process, we will determine 22 whether to utilize our own manufacturing facility or continue to rely on third parties to manufacture commercial quantities of any products that we may successfully develop.
The agreement provides that, subject to the terms and conditions of such agreement, Vertex has the right to conduct all research, development, manufacturing and commercialization activities relating to the specified product 17 candidates and products (including CASGEVY) throughout the world subject to our reserved right to conduct certain activities.
The agreement provides that, subject to the terms and conditions of such agreement, Vertex has the right to conduct all research, development, manufacturing and commercialization activities relating to the specified product candidates and products (including CASGEVY) throughout the world subject to our reserved right to conduct certain activities.
The PHSA emphasizes the importance of manufacturing control for products like biologics whose attributes cannot be precisely defined. 26 For a gene therapy product, the FDA also will not approve the product if the manufacturer is not in compliance with CGTP.
The PHSA emphasizes the importance of manufacturing control for products like biologics whose attributes cannot be precisely defined. For a gene therapy product, the FDA also will not approve the product if the manufacturer is not in compliance with CGTP.
Specifically, the process governing approval of medicinal products in Europe generally follows the same lines as in the United States, although the approval of a medicinal product in the United States is no guarantee of approval of the same product in Europe, either at all or within the same timescale as approval may be granted 31 in the United States.
Specifically, the process governing approval of medicinal products in Europe generally follows the same lines as in the United States, although the approval of a medicinal product in the United States is no guarantee of approval of the same product in Europe, either at all or within the same timescale as approval may be granted in the United States.
The applicant, the FDA, and the FDA’s internal review committee must then review the information submitted, consult with each other, and agree upon a final plan. The FDA or the applicant may request an amendment to the plan at any time.
The applicant, the FDA, and the FDA’s internal review committee must then review the information submitted, 31 consult with each other, and agree upon a final plan. The FDA or the applicant may request an amendment to the plan at any time.
Reference pricing used by various EU Member States, and parallel trade (arbitrage between low-priced and high-priced 36 Member States), can further reduce prices. Special pricing and reimbursement rules may apply to orphan medicinal products.
Reference pricing used by various EU Member States, and parallel trade (arbitrage between low-priced and high-priced Member States), can further reduce prices. Special pricing and reimbursement rules may apply to orphan medicinal products.
Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including exhibits, proxy and information statements and amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act are available on our website free of charge as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC at its website (https://www.sec.gov). 41
Our Annual Reports on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, including exhibits, proxy and information statements and amendments to those reports filed or furnished pursuant to Sections 13(a) and 15(d) of the Exchange Act are available on our website free of charge as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC at its website (https://www.sec.gov). 43
Patients are unlikely to use any products or product 35 candidates we may develop unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of such product candidates.
Patients are unlikely to use any products or product candidates we may develop unless coverage is provided and reimbursement is adequate to cover a significant portion of the cost of such product candidates.
A product may also be subject to official lot release, meaning that the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution.
A product may also be subject to official lot release, meaning that the manufacturer is required to perform certain tests on each 30 lot of the product before it is released for distribution.
The IRA includes several provisions that will impact our business to varying degrees, including provisions that allow the U.S. government to negotiate and set price caps for Medicare Part B and Part D pricing for certain high-cost, single-source drugs and biologics without generic or biosimilar competition; reduce the out-of-pocket cap for Medicare Part D beneficiaries to $2,000 starting in 2025, effectively eliminating the so-called “donut hole” for Medicare Part D; require companies to pay rebates to Medicare for drug prices that increase faster than inflation; and delay the rebate rule that would limit the fees that pharmacy benefit managers can charge, among other areas.
The IRA included several provisions that will impact our business to varying degrees, including provisions that allow the U.S. government to negotiate and set price caps for Medicare Part B and Part D pricing for certain high-cost, single-source drugs and biologics without generic or biosimilar competition; reduce the out-of-pocket spending cap for Medicare Part D beneficiaries to $2,000 starting in 2025, effectively eliminating the so-called “donut hole” for Medicare Part D; require companies to pay rebates to Medicare for drug prices that increase faster than inflation; and delay the rebate rule that would limit the fees that pharmacy benefit managers can charge, among other areas.
In the second quarter of 2021, in connection with the closing of the transaction contemplated by the amendment and restatement of the Vertex JDA, we received a $900 million up-front payment from Vertex.
In the second quarter of 2021, in connection with the closing of the transaction contemplated by the 17 amendment and restatement of the Vertex JDA, we received a $900 million up-front payment from Vertex.
For example, in California, the California Consumer Protection Act, or CCPA, established a comprehensive privacy framework for covered businesses by creating an expanded definition of personal information, establishing new data privacy rights for consumers in the State of California, imposing special rules on the collection of sensitive categories of data, and creating a new and potentially severe statutory damages framework for violations of the CCPA and for businesses that fail to implement reasonable security procedures and practices to prevent data breaches.
For example, in California, the California Consumer Protection Act, or CCPA, established a comprehensive privacy framework for covered businesses by creating an expanded definition of personal information, establishing new data privacy rights for consumers in the State of California, imposing special rules on the collection of sensitive categories of data, and creating a new and potentially severe statutory damages framework for violations of the CCPA and for businesses that fail to implement reasonable security procedures and practices.
This six-month 30 exclusivity may be granted if a BLA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data.
This six-month exclusivity may be granted if a BLA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data.
In exceptional cases, applicants from the academic sector or SMEs (small and medium sized enterprises) may submit an eligibility request at an earlier stage of development if compelling non-clinical data in a relevant model provide early evidence of promising activity, and first in man studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.
In exceptional cases, applicants from the academic sector or SMEs (small and medium sized enterprises) may submit an eligibility request at an earlier stage of development if compelling non-clinical data in a relevant model provide early evidence of promising activity, and first in human studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.
There is no guarantee that a product will be considered by the EMA to be an innovative medicinal product, and products may qualify for data exclusivity.
There is no guarantee that a product will be considered by the EMA to be an innovative medicinal product, and products may not qualify for data exclusivity.
TRACR also received a non-exclusive, worldwide, royalty-free license, including the right to sublicense, to carry out internal pharmaceutical research for therapeutic products outside of the TRACR Field and an exclusive, worldwide, royalty-free sublicense, including the right to sublicense, to research, develop, produce, commercialize and sell therapeutic products relating to the TRACR Field which incorporate any intellectual property that CRISPR develops under its license with Dr.
Additionally, TRACR received a non-exclusive, worldwide, royalty-free license, including the right to sublicense, to carry out internal pharmaceutical research for therapeutic products outside of the TRACR Field and an exclusive, worldwide, royalty-free sublicense, including the right to sublicense, to research, develop, produce, commercialize and sell therapeutic products relating to the TRACR Field which incorporate any intellectual property that CRISPR develops under its license with Dr.
It is unclear how other healthcare reform measures of the Biden administration or other efforts, if any, to challenge, repeal or replace the ACA will impact our business. At the federal level, FDA released implementing regulations in 2020 for how states can build and submit importation plans for drugs from Canada.
It is unclear how other healthcare reform measures of the Trump administration or other efforts, if any, to challenge, repeal or replace the ACA will impact our business. At the federal level, FDA released implementing regulations in 2020 for how states can build and submit importation plans for drugs from Canada.
Data and Market Exclusivity In the EU, innovate medicinal products approved on the basis of a complete independent data package qualify for eight years of data exclusivity upon grant of a marketing authorization and an additional two years of market exclusivity pursuant to Regulation (EC) No 726/2004, as amended, and Directive 2001/83/EC, as amended.
Data and Market Exclusivity In the EU, innovative medicinal products approved on the basis of a complete independent data package qualify for eight years of data exclusivity upon grant of a marketing authorization and an additional two years of market exclusivity pursuant to Regulation (EC) No 726/2004, as amended, and Directive 2001/83/EC, as amended.
In 2017, Vertex exercised its option to co-develop and co-commercialize the hemoglobinopathies program and we entered into a joint development and commercialization agreement with Vertex, which we amended and restated in 2021, pursuant to which, among other things, we are co-developing and co-commercializing CASGEVY for TDT and SCD.
In 2017, Vertex exercised its option to co-develop and co-commercialize the 2 hemoglobinopathies program and we entered into a joint development and commercialization agreement with Vertex, which we amended and restated in 2021, pursuant to which, among other things, we are co-developing and co-commercializing CASGEVY for TDT and SCD. siRNA.
Orphan Drug Designation and Exclusivity Regulation (EC) No 141/2000 and Regulation (EC) No 847/2000 provide that a product can be designated as an orphan medicinal product by the European Commission if its sponsor can establish that: (1) the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five (5) in ten thousand (10,000) persons in the EU when the application is made; or (b) it is unlikely that the product, without benefits derived from orphan status, would generate sufficient return in the EU to justify the necessary investment in its development; (3) there exists no satisfactory method of diagnosis, prevention, or treatment of such condition authorized for marketing in the EU or, if such method exists, the product will be of significant benefit to those affected by that condition.
Orphan Drug Designation and Exclusivity Regulation (EC) No 141/2000 and Regulation (EC) No 847/2000 provide that a product can be designated as an orphan medicinal product by the European Commission, following review by the EMA’s Committee for Orphan Medicinal Products, if its sponsor can establish that: (1) the product is intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition; (2) either (a) such condition affects no more than five (5) in ten thousand (10,000) persons in the EU when the application is made; or (b) it is unlikely that the product, without benefits derived from orphan status, would generate sufficient return in the EU to justify the necessary investment in its development; and (3) there exists no satisfactory method of diagnosis, prevention, or treatment of such condition authorized for marketing in the EU or, if such method exists, the product will be of significant benefit to those affected by that condition.
It overhauls the current system of approvals for clinical trials in the EU. Specifically, the new legislation, which is directly applicable in all EU Member States (meaning that no national implementing legislation in each EU Member State is required), aims at simplifying and streamlining the approval of clinical trials in the EU.
It overhauled the current system of approvals for clinical trials in the EU. Specifically, the new legislation, which is directly applicable in all EU Member States (meaning that no national implementing legislation in each EU Member State is required), aims at simplifying and streamlining the approval of clinical trials in the EU.
In addition, for the years ended December 31, 2022, 2023 and 2024, the agreement allows us to defer a portion of our share of costs under the arrangement if spending on the CASGEVY program exceeds $110.3 million annually.
In addition, for the years ended December 31, 2022, 2023 and 2024, the agreement allowed us to defer a portion of our share of costs under the arrangement if spending on the CASGEVY program exceeds $110.3 million annually.
State and other laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
Certain state laws also govern the privacy and security of health information in some circumstances, many of which are not preempted by HIPAA and differ from each other in significant ways, thus complicating compliance efforts.
It also requires the submission to the EMA, or the relevant competent authorities of a marketing authorization application, or MAA, and granting of a marketing authorization by the EMA or these authorities before the product can be marketed and sold in Europe.
It also requires the submission to the EMA, or the relevant competent authorities of a marketing authorization application, or MAA, and granting of a marketing authorization by the European Commission or these authorities before the product can be marketed and sold in Europe.
The license is exclusive, even as to Dr. Charpentier, except that she retains a non-transferable right to use the technology for her own research purposes and in research collaborations with academic and non-profit partners. The exclusive license is granted only under Dr. Charpentier’s interest in the patent applications and the exclusivity is not granted under any other joint owner’s interest.
Charpentier, except that she retains a non-transferable right to use the technology for her own research purposes and in research collaborations with academic and non-profit partners. The exclusive license granted under the Charpentier License Agreement is granted only under Dr. Charpentier’s interest in the patent applications and the exclusivity is not granted under any other joint owner’s interest.
Clock stops may extend the timeframe of evaluation of an MAA considerably beyond 210 days. Where the CHMP gives a positive opinion, it provides the opinion, together with supporting documentation, to the European Commission, who make the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA's recommendation.
Clock stops may extend the timeframe of evaluation of an MAA considerably beyond 210 days. Where the CHMP gives a positive opinion, it provides the opinion, together with supporting documentation, to the European Commission, which makes the final decision to grant a marketing authorization, which is issued within 67 days of receipt of the EMA's recommendation.
Additionally, the Charpentier License Agreement granted us an exclusive, worldwide, royalty-free sublicense, including the right to sublicense, to research, develop, produce, commercialize and sell therapeutic products relating to the CRISPR Field which incorporate any intellectual property that TRACR develops under its license with Dr. Charpentier. In turn, we granted to Dr.
Additionally, we were granted an exclusive, worldwide, royalty-free sublicense, including the right to sublicense, to research, develop, produce, commercialize and sell therapeutic products relating to the CRISPR Field which incorporate any intellectual property that TRACR develops under its license with Dr. Charpentier. In turn, we granted to Dr.
For further information regarding risks regarding these proceedings, please see generally “ Risk Factors—Risks Related to Intellectual Property .” On December 15, 2016, we entered into a Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement, or the IMA, with California, Vienna, Dr.
For further information regarding risks regarding these proceedings, please see generally “ Risk Factors—Risks Related to Intellectual Property .” In December 2016, we entered into a Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement, or the IMA, with California, Vienna, Dr.
However, notwithstanding that there is no wholesale recognition of EU pharmaceutical legislation under the TCA, under a new international recognition framework mentioned above which was put in place by the MHRA on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a Great Britain marketing authorization.
However, 36 notwithstanding that there is no wholesale recognition of EU pharmaceutical legislation under the TCA, under a new international recognition framework mentioned above which was put in place by the MHRA on January 1, 2024, the MHRA may take into account decisions on the approval of a marketing authorization from the EMA (and certain other regulators) when considering an application for a UK marketing authorization.
Additionally, in 2023, we entered into a non-exclusive license agreement with Vertex for Vertex to utilize certain of our gene-editing intellectual property to exploit certain products for the diagnosis, treatment or prevention of diabetes type 1, diabetes type 2 or insulin dependent/requiring diabetes throughout the world.
In addition, in March 2023, we entered into a non-exclusive license agreement with Vertex for Vertex to utilize certain of our gene-editing intellectual property to exploit certain products for the diagnosis, treatment or prevention of diabetes type 1, diabetes type 2 or insulin dependent/requiring diabetes throughout the world.
CTX310 Our lead in vivo product candidate, CTX310, targets the gene encoding angiopoietin-related protein 3, or ANGPTL3, for the treatment and prevention of CVD. ANGPTL3 plays an important role in lipid metabolism by inhibiting an enzyme called lipoprotein lipase, or LPL.
CTX310 Our most advanced in vivo product candidate, CTX310, targets the gene encoding angiopoietin-related protein 3, or ANGPTL3, for the treatment and prevention of CVD. ANGPTL3 plays an important role in lipid metabolism by inhibiting an enzyme called lipoprotein lipase, or LPL.
We foster a strong relationship with and among our employees with ongoing efforts such as employee surveys, training and development programs, and other programs, including skill development courses, manager training, leadership development opportunities, tuition reimbursement and robust online course training libraries for reference on a myriad of development topics.
We foster a strong relationship with and among our employees with ongoing efforts such as training and development programs, including skill development courses, manager training, leadership development opportunities, tuition reimbursement and robust online course training libraries for reference on a myriad of development topics.
Non-integrating viral gene therapy platforms, such as AAV, may have limited durability because they do not permanently change the genome and have limited efficacy upon re-administration due to resulting immune responses. Integrating viral gene therapy platforms, such as lentivirus, permanently alter the genome but do so randomly, which leads to the potential for undesirable mutations.
Non-integrating viral gene therapy platforms, such as adenovirus-associated vectors, or AAV, may have limited durability because they do not permanently change the genome and have limited efficacy upon re-administration due to resulting immune responses. Integrating viral gene therapy platforms, such as lentivirus, permanently alter the genome but do so randomly, which leads to the potential for undesirable mutations.
The regulatory regime in Great Britain therefore aligns in many ways with EU regulations, however it is possible that these regimes will more significantly diverge in future now that Great Britain’s regulatory system is independent from the EU and the TCA does not provide for mutual recognition of UK and EU pharmaceutical legislation.
The regulatory regime in the UK therefore aligns in many ways with EU regulations, however it is possible that these regimes will more significantly diverge in future now that the UK’s regulatory system is independent from the EU and the TCA does not provide for mutual recognition of UK and EU pharmaceutical legislation.
Charpentier, Intellia Therapeutics, Caribou, ERS Genomics Ltd., or ERS, and our wholly-owned subsidiary TRACR Hematology Ltd., or TRACR. Under the IMA, California and Vienna retroactively consent to Dr. Charpentier’s licensing of her rights to the CRISPR/Cas9 intellectual property, pursuant to our license with Dr. Charpentier, to us, TRACR, and ERS, in the United States and globally.
Charpentier, Intellia, Caribou, ERS Genomics Ltd., or ERS, and our wholly-owned subsidiary TRACR Hematology Ltd., or TRACR. Under the IMA, California and Vienna retroactively consent to Dr. Charpentier’s licensing of her rights to the CRISPR/Cas9 intellectual property to CRISPR and TRACR pursuant to the Charpentier License Agreement and to ERS, in the United States and globally.
Periods of Authorization and Renewals A centralized marketing authorization is valid for five years, in principle, and it may be renewed after five years on the basis of a reevaluation of the risk-benefit balance by the EMA or by the competent authority of the authorizing EU Member State for a 33 nationally authorized product.
Periods of Authorization and Renewals In the European Union, a marketing authorization is valid for five years, in principle, and it may be renewed after five years on the basis of a reevaluation of the risk-benefit balance by the EMA or by the competent authority of the authorizing EU Member State for a nationally authorized product.
We and Vertex continue to investigate CASGEVY, including (1) three clinical trials designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12 to 35 with severe SCD and TDT, respectively, (2) two clinical trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and (3) long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion.
We and Vertex continue to investigate CASGEVY, including in clinical trials designed to assess the safety and efficacy of a 5 single dose of CASGEVY in patients ages 12 to 35 with severe SCD and TDT, respectively, two pivotal trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion.
Charpentier an exclusive license with the obligation to sublicense to TRACR any intellectual property we develop under the license with Dr. Charpentier for treatment and prevention of hemoglobinopathies in humans, including, without limitation, sickle cell disease and thalassemia. Under the terms of the Charpentier License Agreement, as consideration for the license, Dr.
Charpentier an exclusive license with the obligation to sublicense to TRACR any intellectual property we develop under the license with Dr. Charpentier for treatment and prevention of hemoglobinopathies in humans, including, without limitation, sickle cell disease and thalassemia.
To turn this promise into reality, we have built a broad and diversified pipeline of product candidates leveraging CRISPR/Cas gene editing. 4 Our Pipeline The following table summarizes the status of our product development pipeline: Hemoglobinopathies Hemoglobinopathies are a diverse group of inherited blood disorders that result from variations in the synthesis or structure of hemoglobin.
To turn this promise into reality, we have built a broad and diversified pipeline of product candidates leveraging gene-based technologies, including CRISPR/Cas9 gene editing technology. 4 Our Pipeline The following table summarizes the status of our product development pipeline: Hemoglobinopathies Hemoglobinopathies are a diverse group of inherited blood disorders that result from variations in the synthesis or structure of hemoglobin.
These patent families encompass filings covering our development programs (such as composition of matter, method of use, manufacturing processes, dosing and formulations), the use and improvement modifications of CRISPR/Cas9 systems for gene editing and next generation editing systems (such as improvements to component systems including nucleases and single or modified gRNAs), in vivo targets, technologies for delivering protein/nucleic acid complexes and RNA into cells (such as improved viral vector systems), and technology relevant to stem cell-based therapies and cancer therapies.
These patent families encompass filings covering our development programs (such as composition of matter, method of use, manufacturing processes, dosing and formulations), the use and improvement modifications of CRISPR/Cas9 systems for gene editing and next generation editing systems (such as improvements to component systems including nucleases and single or modified gRNAs, as well as novel Cas9 and polymerase variants and codon-optimized novel constructs), in vivo targets, technologies for delivering protein/nucleic acid complexes and RNA into cells (such as improved viral vector or lipid nanoparticle systems), and technology relevant to stem cell-based therapies and cancer therapies.
Competition The biotechnology and pharmaceutical industries, including in the gene editing, gene therapy and cell therapy fields, are characterized by rapidly advancing technologies, intense competition and a strong emphasis on intellectual property and proprietary 22 products.
Competition The biotechnology and pharmaceutical industries, including in the gene editing, gene therapy, nucleic acids therapies, and cell therapy fields, are characterized by rapidly advancing technologies, intense competition and a strong emphasis on intellectual property and proprietary products.
Finally, the marketing and promotion of authorized products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the EU. The advertising of prescription-only medicines to the general public is not permitted in the EU. The aforementioned EU rules are generally applicable in the EEA.
Finally, the marketing and promotion of authorized products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the EU. The advertising of prescription-only medicines to the general public is not permitted in the EU.
An orphan designation provides a number of benefits, including fee reductions, regulatory assistance, and the ability to apply for a centralized marketing authorization. The grant of a marketing authorization for an orphan medicinal product leads to a ten-year period of market exclusivity.
An orphan designation provides a number of benefits, including fee reductions, regulatory assistance, and the ability to apply for a centralized marketing authorization. The grant of a marketing authorization for an orphan medicinal product leads to a ten-year period of market exclusivity fo r the authorized therapeutic indication.
The autologous CAR T cells used successfully in autoimmune diseases to date appear to cause a B cell “reset” following deep B cell depletion whereby reconstituted B cells do not express high levels of autoantibodies. We believe that CTX112 has the potential to produce a similar B cell “reset”.
Zugocabtagene geleucel Autoimmune disease The autologous CAR T cells used successfully in autoimmune diseases to date appear to cause a B cell “reset” following deep B cell depletion whereby reconstituted B cells do not express high levels of autoantibodies. We believe that zugo-cel has the potential to produce a similar B cell “reset”.
CTX112 and CTX131 each incorporate two novel gene edits. These edits—knock-out of Regnase-1 and knock-out of transforming growth factor-beta receptor type 2, or TGFBR2—are designed to enhance CAR T potency and reduce CAR T exhaustion. Editing Regnase-1 removes an intrinsic “brake” on T cell function while editing TGFBR2 removes a key extrinsic “brake” on T cell anti-tumor activity.
These edits—knock-out of Regnase-1 and knock-out of transforming growth factor-beta receptor type 2, or TGFBR2—are designed to enhance CAR T potency and reduce CAR T exhaustion. Editing Regnase-1 removes an intrinsic “brake” on T cell function while editing TGFBR2 removes a key extrinsic “brake” on T cell anti-tumor activity.
To date, CASGEVY has 1 been approved in the United States, European Union, Great Britain, Canada, Switzerland, Kingdom of Saudi Arabia, Kingdom of Bahrain and the United Arab Emirates for the treatment of eligible patients 12 years and older with SCD or TDT.
To date, CASGEVY has been approved by regulatory authorities in the United States, European Union, Great Britain, Canada, Switzerland, Kingdom of Saudi Arabia, Kingdom of Bahrain, Qatar, the United Arab Emirates and Kuwait for the treatment of eligible patients 12 years and older with SCD or TDT.
Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026. This deadline was further pushed back to January 1, 2027 by the Bipartisan Safer Communities Act and later to January 1, 2032 by the Inflation Reduction Act of 2022 ("IRA").
Pursuant to court order, the removal and addition of the aforementioned safe harbors were delayed and recent legislation imposed a moratorium on implementation of the rule until January 1, 2026. This deadline was later pushed back to January 1, 2032 by the Inflation Reduction Act of 2022 (“IRA”).
For further information regarding the effects of joint ownership in the United States and in other jurisdictions worldwide, please see “ Risk Factors — The Intellectual Property That Protects Our Core Gene Editing Technology Is Jointly Owned, And Our License Is From Only One Of The Joint Owners, Materially Limiting Our Rights In The United States And In Other Jurisdictions .” CRISPR-Owned Intellectual Property In addition to the worldwide patent portfolio we in-license from Dr.
For further information regarding the effects of joint ownership in the United States and in other jurisdictions worldwide, please see “ Risk Factors — The Intellectual Property That Protects Our Core Gene Editing Technology Is Jointly Owned, And Our License Is From Only One Of The Joint Owners, Materially Limiting Our Rights In The United States And In Other Jurisdictions .” License Agreements License Agreements With Dr.
We have the right to terminate the agreement at will upon 60 days’ written notice to Dr. Charpentier. We and Dr. Charpentier may terminate the agreement upon 90 days’ notice in the event of a material breach by the other party, which is not cured during the 90-day notice period. Dr.
We and TRACR have the right to terminate the agreement at will upon 60 days’ written notice to Dr. Charpentier. Each Charpentier License Agreement may be terminated by either party thereto upon 90 days’ notice in the event of a material breach by the other party, which is not cured during the 90-day notice period. Dr.
Overall, our wholly-owned intellectual property estate includes over one hundred (100) active patent families and over seventy (70) granted or allowed patents, including in the United States, China, Europe, South Africa, Australia, Canada, China, Japan, Mexico and other selected countries in South America, the Middle East and Asia.
Overall, our wholly-owned intellectual property estate includes approximately eighty (80) active patent families and over one hundred twenty (120) granted or allowed patents, including in the United States, China, Europe, South Africa, Australia, Canada, China, Japan, Mexico and other selected countries in South America, the Middle East and Asia.
Dyslipidemias are characterized by abnormally high levels of lipids, including cholesterol, lipoproteins and triglycerides, in the bloodstream. Three of the most common dyslipidemias are hypercholesterolemia, hypertriglyceridemia and elevated Lp(a). Today’s chronic care treatment model of CVD involves daily medication, weekly injection, multiple infusions annually and/or surgical interventions. This model places a heavy burden on patients and the healthcare system.
Dyslipidemias are characterized by abnormally high levels of lipids, including cholesterol, lipoproteins and triglycerides, in the bloodstream. Three of the most common dyslipidemias are hypercholesterolemia, hypertriglyceridemia and elevated lipoprotein (a), or Lp(a). Today’s chronic care treatment model of CVD involves daily medication, weekly injection, multiple infusions annually and/or surgical interventions.
In hypercholesterolemia, high levels of LDL-C accumulate in blood vessels, leading to atherosclerosis. Treatment aims to reduce LDL-C levels to below 100 mg/dL with 70 mg/dL as the ultimate goal, but some patients cannot achieve this level of reduction through existing means. Patients with LDL-C levels above 200 mg/dL are considered to have familial hypercholesterolemia (FH).
Treatment aims to reduce LDL-C levels to below 100 mg/dL with 70 mg/dL as the ultimate goal, but some patients cannot achieve this level of reduction through existing means. Patients with LDL-C levels above 200 mg/dL are considered to have familial hypercholesterolemia, or FH.
HoFH patients have the most severe phenotype, with LDL-C levels usually exceeding 400 mg/dL. HoFH patients often suffer from CVD early in life and have an average life expectancy of 33 years if untreated. HoFH has a prevalence of 1 in 200,000 to 1,000,000 adults. Hypertriglyceridemia Hypertriglyceridemia is clinically defined as having triglyceride levels above l50 mg/dL.
HoFH patients have the most severe phenotype, with LDL-C levels usually exceeding 400 mg/dL. HoFH patients often suffer from CVD early in life and have an average life expectancy of 33 years if untreated. HoFH has a prevalence of 1 in 200,000 to 1,000,000 adults.
The prevalence of FCS is 1 in 200,000 to 300,000 individuals in the United States and EU. MCS is polygenic in nature, meaning that the genetic underpinnings causing the disease to vary among individuals, and is clinically defined as having triglyceride levels between 150 and 885 mg/dL. MCS has a prevalence of 1 in 600 to 1,000 individuals.
MCS is polygenic in nature, meaning that the genetic underpinnings causing the disease to vary among individuals, and is clinically defined as having triglyceride levels between 150 and 885 mg/dL. MCS has a prevalence of 1 in 250 to 600 individuals.
CTX112 Immuno-oncology We are investigating CTX112 in an ongoing clinical trial designed to assess the safety and efficacy of CTX112 in adult patients with relapsed or refractory B-cell malignancies who have received at least two prior lines of therapy.
Summary of Zugo-cel Clinical Efficacy in SLE (N=2) Immuno-oncology We are investigating zugo-cel in an ongoing clinical trial designed to assess the safety and efficacy of zugo-cel in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy.

… 357 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

214 edited+61 added−49 removed637 unchanged
Biggest changeOur results of operations could be adversely affected by general conditions in the global economy, disruption of global financial markets and a recession or market correction, including, for example, as a result of the coronavirus pandemic, political unrest, including as a result of geopolitical tension such as a deterioration in the relationship between the United States and China, escalation of tensions between China and Taiwan, the ongoing military conflict between Russia and Ukraine and related sanctions imposed against Russia, or the Israel-Hamas war, and other global macroeconomic factors such as inflation.
Biggest changeOur business, financial condition and results of operations could be adversely affected by general conditions in the global economy, disruption of global financial markets and a recession or market correction, including, for example, as a result of uncertain trade policy, political unrest, including as a result of geopolitical tension such as a deterioration in the relationship between the United States and China, escalation of tensions between China and Taiwan, the ongoing military conflict between Russia and Ukraine and related sanctions imposed against Russia, or the Israel-Hamas war, and other global macroeconomic factors such as inflation, interest rate and currency rate fluctuations, tariffs, changes in or disruptions of certain U.S. governmental agencies, such as the FDA, whether due to a potential or actual U.S. federal government shutdown or otherwise, new laws and regulations or amendments to existing laws and regulations in the U.S. and foreign countries.
The FDA, MHRA and the EMA have each expressed interest in further regulating biotechnology, including gene therapy and genetic testing. For example, the EMA advocates a risk-based approach to the development of a gene therapy product.
The FDA, MHRA and the EMA have each expressed interest in further regulating biotechnology, including gene therapy and genetic testing. For example, the EMA advocates for a risk-based approach to the development of a gene therapy product.
Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects, and limit our ability to research, develop and obtain approval of product candidates, or to commercialize products.
Any of these events could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and prospects, and limit our ability to research, develop and obtain approval of product candidates, or to commercialize products.
The assignment of intellectual property rights may not be self-executing, or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property.
The assignment of intellectual property rights may not be self-executing, or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against us, to determine the ownership of what we regard as our intellectual property.
Our future capital requirements will depend on, and could increase significantly as a result of, many factors, including: • the scope, progress, results and costs of clinical trials, drug discovery, preclinical development and laboratory testing for our wholly owned and partnered product candidates; • the scope, prioritization and number of our research and development programs; • the costs, timing and outcome of regulatory review of our product candidates; • the costs of establishing and maintaining a supply chain for the development and manufacture of our product candidates; • the success of our collaborations with Vertex; • our ability to establish and maintain additional collaborations on favorable terms, if at all; • the achievement of milestones or occurrence of other developments that trigger payments under any additional collaboration or license agreements we obtain; • the extent to which we are obligated to reimburse, or entitled to reimbursement of various expenses, including clinical trial, development and commercialization costs, under our current or future collaboration agreements, if any; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; • the costs of fulfilling our obligations under the Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement to reimburse other parties for costs incurred in connection with the prosecution and maintenance of associated patent rights; • the extent to which we acquire or in-license other product candidates, intellectual property and technologies; • the costs of establishing, expanding or contracting for manufacturing capabilities if we obtain regulatory approvals to manufacture our product candidates; • the costs of establishing or contracting for sales and marketing capabilities if we obtain regulatory approvals to market our product candidates; and • our ability to establish and maintain healthcare coverage and adequate reimbursement.
Our future capital requirements will depend on, and could increase significantly as a result of, many factors, including: • the scope, progress, results and costs of clinical trials, drug discovery, preclinical development and laboratory testing for our wholly-owned and partnered product candidates; • the scope, prioritization and number of our research and development programs; • the costs, timing and outcome of regulatory review of our product candidates; • the costs of establishing and maintaining a supply chain for the development and manufacture of our product candidates; • the success of our collaborations with Vertex and Sirius; • our ability to establish and maintain additional collaborations on favorable terms, if at all; • the achievement of milestones or occurrence of other developments that trigger payments under any additional collaboration or license agreements we obtain; • the extent to which we are obligated to reimburse, or entitled to reimbursement of various expenses, including clinical trial, development, manufacturing and commercialization costs, under our current or future collaboration agreements, if any; • the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our intellectual property rights and defending intellectual property-related claims; • the costs of fulfilling our obligations under the Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement to reimburse other parties for costs incurred in connection with the prosecution and maintenance of associated patent rights; • the extent to which we acquire or in-license other product candidates, intellectual property and technologies; • the costs of establishing, expanding or contracting for manufacturing capabilities if we obtain regulatory approvals to manufacture our product candidates; • the costs of establishing or contracting for sales and marketing capabilities if we obtain regulatory approvals to market our product candidates; and • our ability to establish and maintain healthcare coverage and adequate reimbursement.
In addition, the market price for our common shares may be influenced by many factors, including: • the success of existing or new competitive products or technologies; • the timing and results of any product candidates that we may develop; • commencement or termination of collaborations for our product development and research programs; • failure or discontinuation of any of our product development and research programs; • results of preclinical studies, clinical trials, or regulatory approvals of product candidates of our competitors, or announcements about new research programs or product candidates of our competitors; • developments or changing views regarding the use of genomic products, including those that involve gene editing; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents, or other proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to any of our research programs, clinical development programs, or product candidates that we may develop; • the results of our efforts to discover, develop, acquire or in-license additional product candidates or products; • actual or anticipated changes in estimates as to financial results, development timelines, or recommendations by securities analysts; • announcement or expectation of additional financing efforts; • sales of our common shares by us, our insiders, or other shareholders; • expiration of market stand-off or lock-up agreements; • variations in our financial results or those of companies that are perceived to be similar to us; • changes in estimates or recommendations by securities analysts, if any, that cover our common shares; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; and • the other factors described in this “Risk Factors” section.
In addition, the market price for our common shares may be influenced by many factors, including: • the success of existing or new competitive products or technologies; • the timing and results of any product candidates that we may develop; • commencement or termination of collaborations for our product development and research programs; • failure or discontinuation of any of our product development and research programs; • results of preclinical studies, clinical trials, or regulatory approvals of product candidates of our competitors, or announcements about new research programs or product candidates of our competitors; • developments or changing views regarding the use of genomic products, including those that involve gene editing; • regulatory or legal developments in the United States and other countries; • developments or disputes concerning patent applications, issued patents, or other proprietary rights; • the recruitment or departure of key personnel; • the level of expenses related to any of our research programs, clinical development programs, or product candidates that we 90 may develop; • the results of our efforts to discover, develop, acquire or in-license additional product candidates or products; • actual or anticipated changes in estimates as to financial results, development timelines, or recommendations by securities analysts; • announcement or expectation of additional financing efforts; • sales of our common shares by us, our insiders, or other shareholders; • expiration of market stand-off or lock-up agreements; • variations in our financial results or those of companies that are perceived to be similar to us; • changes in estimates or recommendations by securities analysts, if any, that cover our common shares; • changes in the structure of healthcare payment systems; • market conditions in the pharmaceutical and biotechnology sectors; • general economic, industry and market conditions; and • the other factors described in this “Risk Factors” section.
For example: • others may be able to make gene therapy products that are similar to any product candidates we may develop or utilize similar gene therapy technology but that are not covered by the claims of the patents that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; • it is possible that our pending licensed patent applications or those that we may own in the future will not lead to issued patents; • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors; 79 • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
For example: • others may be able to make gene therapy products that are similar to any product candidates we may develop or utilize similar gene therapy technology but that are not covered by the claims of the patents that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or may own in the future; • we, or our license partners or current or future collaborators, might not have been the first to file patent applications covering certain of our or their inventions; • others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights; • it is possible that our pending licensed patent applications or those that we may own in the future will not lead to issued patents; • issued patents that we hold rights to may be held invalid or unenforceable, including as a result of legal challenges by our competitors; • our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets; • we may not develop additional proprietary technologies that are patentable; • the patents of others may harm our business; and • we may choose not to file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.
Accordingly, our future results could be harmed by 89 a variety of factors, including: • economic weakness, including inflation, or political instability in particular non-U.S. economies and markets; • differing regulatory requirements for drug approvals in non-U.S. countries; • potentially reduced protection for intellectual property rights; • difficulties in compliance with non-U.S. laws and regulations; • changes in non-U.S. regulations and customs, tariffs and trade barriers; • changes in non-U.S. currency exchange rates and currency controls; • changes in a specific country’s or region’s political or economic environment; • trade protection measures, import or export licensing requirements or other restrictive actions by U.S. or non-U.S. governments; • negative consequences from changes in tax laws; • compliance with tax, employment, immigration and labor laws for employees living or traveling outside the United States; • workforce uncertainty in countries where labor unrest is more common than in the United States; • difficulties associated with staffing and managing international operations, including differing labor relations; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities outside the United States; and • business interruptions resulting from geo-political actions, including war and terrorism, or natural disasters including floods and fires.
Accordingly, our future results could be harmed by a variety of factors, including: • economic weakness, including inflation, or political instability in particular non-U.S. economies and markets; • differing regulatory requirements for drug approvals in non-U.S. countries; • potentially reduced protection for intellectual property rights; • difficulties in compliance with non-U.S. laws and regulations; • changes in non-U.S. regulations and customs, tariffs and trade barriers; • changes in non-U.S. currency exchange rates and currency controls; • changes in a specific country’s or region’s political or economic environment; • trade protection measures, import or export licensing requirements or other restrictive actions by U.S. or non-U.S. governments; • negative consequences from changes in tax laws; • compliance with tax, employment, immigration and labor laws for employees living or traveling outside the United States; • workforce uncertainty in countries where labor unrest is more common than in the United States; • difficulties associated with staffing and managing international operations, including differing labor relations; • production shortages resulting from any events affecting raw material supply or manufacturing capabilities outside the United States; and • business interruptions resulting from geo-political actions, including war and terrorism, or natural disasters including floods and fires.
Our reliance on a limited number of third-party manufacturers exposes us to a number of risks, including the following: • we may be unable to identify manufacturers on acceptable terms or at all because the number of potential manufacturers is limited; • a new manufacturer would have to be educated in, or develop substantially equivalent processes for, the production of our product candidates; • a change in manufacturers or certain changes in manufacturing processes/procedures will require that we conduct a manufacturing comparability study to verify that any new manufacturer or manufacturing process/procedures will produce our product candidate according to the specifications previously submitted to the FDA or other regulatory authority, and such study may be unsuccessful; • our third-party contract manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; • our third-party contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; • our third-party contract manufacturers may not perform as agreed, may prioritize other customers, may not devote sufficient resources to our product candidates or may not remain in the contract manufacturing business for the time required to supply our clinical trials or commercial needs; • manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies or other regulatory authority to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards and we have no control over third-party manufacturers’ compliance with these regulations and standards; • we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; • our third-party contract manufacturers could breach or terminate their agreements with us; • raw materials and components used in the manufacturing process, particularly those for which we have no other source or supplier, may not be available or may not be suitable or acceptable for use due to material or component defects; • our third-party contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; • our third-party contract manufacturers may have unacceptable or inconsistent product quality success rates and yields, and we have no direct control over our contract manufacturers’ ability to maintain adequate quality control, quality assurance and qualified personnel; and • our third-party contract manufacturers may manufacture defective or otherwise dangerous products that could result in injury to consumers during clinical trials or once commercialized for sale to the public, if not discovered by us.
In addition, our reliance on a limited number of third-party manufacturers exposes us to a number of risks, including the following: • we may be unable to identify manufacturers on acceptable terms or at all because the number of potential manufacturers is limited; • a new manufacturer would have to be educated in, or develop substantially equivalent processes for, the production of our product candidates; • a change in manufacturers or certain changes in manufacturing processes and procedures will require that we conduct a manufacturing comparability study to verify that any new manufacturer or manufacturing processes and procedures will produce our product candidate according to the specifications previously submitted to the FDA or other regulatory authority, and such study may be unsuccessful; • our third-party contract manufacturers might be unable to timely manufacture our product candidates or produce the quantity and quality required to meet our clinical and commercial needs, if any; • our third-party contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; • our third-party contract manufacturers may not perform as agreed, may prioritize other customers, may not devote sufficient resources to our product candidates or may not remain in the contract manufacturing business for the time required to supply our clinical trials or commercial needs; • manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies or other regulatory authorities to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards and we have no control over third-party manufacturers’ compliance with these regulations and standards; • we may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; • our third-party contract manufacturers could breach or terminate their agreements with us; • raw materials and components used in the manufacturing process, particularly those for which we have no other source or supplier, may not be available or may not be suitable or acceptable for use due to material or component defects; • our third-party contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; • our third-party contract manufacturers may have unacceptable or inconsistent product quality success rates and yields, and we have no direct control over our contract manufacturers’ ability to maintain adequate quality control, quality assurance and qualified personnel; and • our third-party contract manufacturers may manufacture defective or otherwise dangerous products that could result in injury to consumers during clinical trials or once commercialized for sale to the public, if not discovered by us.
The GDPR imposes a 85 broad range of strict requirements on companies subject to the GDPR, including requirements relating to processing special categories of personal data (such as health data), where required obtaining consent of the individuals to whom the personal data relates, having legal bases and/or conditions for processing personal data, including to the United States, providing details to those individuals regarding the processing of their personal data, implementing safeguards to protect the security and confidentiality of personal data, having data processing agreements with third parties who process personal data, responding to individuals’ requests to exercise their rights in respect of their personal information, reporting security breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments for high risk processing activities, ensuring certain accountability measures and record-keeping.
The GDPR imposes a broad range of strict requirements on companies subject to the GDPR, including requirements relating to processing special categories of personal data (such as health data), where required obtaining consent of the individuals to whom the personal data relates, having legal bases and/or conditions for processing personal data, including to the United States, providing details to those individuals regarding the processing of their personal data, implementing safeguards to protect the security and confidentiality of personal data, having data processing agreements with third parties who process personal data, responding to individuals’ requests to exercise their rights in respect of their personal information, reporting security breaches involving personal data to the competent national data protection authority and affected individuals, appointing data protection officers, conducting data protection impact assessments for high risk processing activities, ensuring certain accountability measures and record-keeping.
In addition, the U.S. government has the right to require us to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if it determines that: (i) adequate steps have not been taken to achieve practical application of the invention in the field of use; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations, also referred to as “march-in rights.” The U.S. government also has the right to take title to these inventions if we, or the applicable contractor, fail to disclose the 77 invention to the government and fail to file an application to register the intellectual property within specified time limits.
In addition, the U.S. government has the right to require us to grant exclusive, partially exclusive, or non-exclusive licenses to any of these inventions to a third party if it determines that: (i) adequate steps have not been taken to achieve practical application of the invention in the field of use; (ii) government action is necessary to meet public health or safety needs; or (iii) government action is necessary to meet requirements for public use under federal regulations, also referred to as “march-in rights.” The U.S. government also has the right to take title to these inventions if we, or the applicable contractor, fail to disclose the invention to the government and fail to file an application to register the intellectual property within specified time limits.
A “U.S. holder” is a beneficial owner of common shares that is (or is treated as), for U.S. federal income tax purposes: • an individual who is a citizen or resident of the United States; • a corporation, or other entity that is treated as a corporation for U.S. federal income tax purposes, created or organized in or under the laws of the United States, any state thereof, or the District of Columbia; • an estate, the income of which is subject to U.S. federal income taxation regardless of its source; or • a trust, if (a) a court within the United States is able to exercise primary supervision over its administration and one or more U.S. persons have the authority to control all of the substantial decisions of such trust, or (b) the trust has a valid election in effect under applicable U.S.
A “U.S. holder” is a beneficial owner of common shares that is (or is treated as), for U.S. federal income tax purposes: • an individual who is a citizen or resident of the United States; • a corporation, or other entity that is treated as a corporation for U.S. federal income tax purposes, created or organized in or under the laws of the United States, any state thereof, or the District of Columbia; 86 • an estate, the income of which is subject to U.S. federal income taxation regardless of its source; or • a trust, if (a) a court within the United States is able to exercise primary supervision over its administration and one or more U.S. persons have the authority to control all of the substantial decisions of such trust, or (b) the trust has a valid election in effect under applicable U.S.
In addition, (i) corporate and individual shareholders who are resident in Switzerland for tax purposes, (ii) corporate and individual shareholders who are not resident in Switzerland, and who, in each case, hold their shares as part of a trade or business carried on in Switzerland through a permanent establishment with fixed place of business situated in Switzerland for tax purposes and (iii) Swiss resident private individuals who, for income tax purposes, are classified as “professional securities dealers” for reasons of, 83 inter alia, frequent dealing, or leveraged investments, in shares and other securities (collectively, “Domestic Commercial Shareholders”) are in principle eligible for a full refund or credit against income tax of the Swiss withholding tax if they duly report the underlying income in their income statements or income tax return, as the case may be.
In addition, (i) corporate and individual shareholders who are resident in Switzerland for tax purposes, (ii) corporate and individual shareholders who are not resident in Switzerland, and who, in each case, hold their shares as part of a trade or business carried on in Switzerland through a permanent establishment with fixed place of business situated in Switzerland for tax purposes and (iii) Swiss resident private individuals who, for income tax purposes, are classified as “professional securities dealers” for reasons of, inter alia, frequent dealing, or leveraged investments, in shares and other securities (collectively, “Domestic Commercial Shareholders”) are in principle eligible for a full refund or credit against income tax of the Swiss withholding tax if they duly report the underlying income in their income statements or income tax return, as the case may be.
The success of our product candidates will depend on several factors, including the following: • successful enrollment in, and completion of, clinical trials and preclinical studies; • sufficiency of our financial and other resources to complete the necessary clinical trials and preclinical studies; • ability to develop safe and effective delivery mechanisms for our in vivo therapeutic programs; • ability to identify optimal RNA sequences to guide genomic editing; • maintenance of current, and entry into additional, collaborations to further the development of our product candidates; • approval of INDs, CTAs or their equivalents for our product candidates to commence clinical trials; • successful data from our clinical programs that support an acceptable risk-benefit profile of our product candidates for the intended patient populations; • receipt of regulatory and marketing approvals from applicable regulatory authorities; • establishing and maintaining arrangements with third-party manufacturers for clinical and commercial supply and, where applicable, commercial manufacturing capabilities; • successful development of our internal manufacturing processes and transfer to larger-scale facilities operated by either a third-party contract manufacturing organization or by us; • establishment and maintenance of patent and trade secret protection or regulatory exclusivity for our product candidates; • commercial launch of our product candidates, if and when approved, whether alone or in collaboration with others; • acceptance of our product candidates, if and when approved, by patients, the medical community and third-party payors; • effective competition with other therapies and treatment options; • establishment and maintenance of healthcare coverage and adequate reimbursement; • enforcement and defense of intellectual property rights and claims; 45 • maintenance of a continued acceptable safety profile of our product candidates following approval; and • achieving desirable medicinal properties for the intended indications.
The success of our product candidates will depend on several factors, including the following: • successful enrollment in, and completion of, clinical trials and preclinical studies; • sufficiency of our financial and other resources to complete the necessary clinical trials and preclinical studies; • ability to develop safe and effective delivery mechanisms for our in vivo therapeutic programs; • ability to identify optimal RNA sequences to guide genomic editing; • maintenance of current, and entry into additional, collaborations to further the development of our product candidates; • approval of INDs, CTAs or their equivalents for our product candidates to commence clinical trials; • successful data from our clinical programs that support an acceptable risk-benefit profile of our product candidates for the intended patient populations; • receipt of regulatory and marketing approvals from applicable regulatory authorities; • establishing and maintaining arrangements with third-party manufacturers for clinical and commercial supply and, where applicable, commercial manufacturing capabilities; • successful development of our internal manufacturing processes and transfer to larger-scale facilities operated by either a third-party contract manufacturing organization or by us; • establishment and maintenance of patent and trade secret protection or regulatory exclusivity for our product candidates; • commercial launch of our product candidates, if and when approved, whether alone or in collaboration with others; • acceptance of our product candidates, if and when approved, by patients, the medical community and third-party payors; 47 • effective competition with other therapies and treatment options; • establishment and maintenance of healthcare coverage and adequate reimbursement; • enforcement and defense of intellectual property rights and claims; • maintenance of a continued acceptable safety profile of our product candidates following approval; and • achieving desirable medicinal properties for the intended indications.
Furthermore, if we or others later identify undesirable side effects caused by any approved product or product candidate that we develop alone or with our collaborators, several potentially significant negative consequences could result, including: • regulatory authorities may revoke licenses or suspend, vary or withdraw approvals of such product or product candidate; • regulatory authorities may require additional warnings on the label; • we may be required to change the way a product or product candidate is administered or conduct additional clinical trials; • we could be sued and held liable for harm caused to patients; and • our reputation may suffer.
Furthermore, if we or others later identify undesirable side effects caused by any approved product or product candidate that we develop alone or with our collaborators, several potentially significant negative consequences could result, including: • regulatory authorities may revoke licenses or suspend, vary or withdraw approvals of such product or product candidate; • regulatory authorities may require additional warnings on the label; • we may be required to change the way a product or product candidate is administered or conduct additional clinical trials; 51 • we could be sued and held liable for harm caused to patients; and • our reputation may suffer.
The degree of market acceptance of gene therapy products and, in particular, our product candidates, if approved for commercial sale, will depend on several factors, including: • the efficacy, durability and safety of such product candidates as demonstrated in any future clinical trials; • the potential and perceived advantages of product candidates over alternative treatments; • the cost of treatment relative to alternative treatments; • the clinical indications for which the product candidate is approved by FDA, the EMA or other regulatory authorities; • patient awareness of, and willingness to seek, genotyping; • the willingness of healthcare providers to prescribe new therapies and the target patient population to try new therapies; • our and our partners efforts to educate healthcare providers and patients about our products; • the prevalence and severity of any side effects; • product labeling or product insert requirements of FDA, the EMA or other regulatory authorities, including any limitations or warnings contained in a product’s approved labeling; • relative convenience and ease of administration; • the strength of marketing and distribution support; • the timing of market introduction of competitive products; • adverse publicity concerning our products or competing products and treatments, including social and ethical controversies in the field of gene editing; • establishment of authorized treatment centers; • sufficient third-party payor coverage and reimbursement; and • approval of new products or technologies that are more favorably received than our products, are more cost effective or render our products obsolete.
The degree of market acceptance of gene therapy products and, in particular, our product candidates, if approved for commercial sale, will depend on several factors, including: • the efficacy, durability and safety of such product candidates as demonstrated in any future clinical trials; • the potential and perceived advantages of product candidates over alternative treatments; • the cost of treatment relative to alternative treatments; • the clinical indications for which the product candidate is approved by FDA, the European Commission or other regulatory authorities; • patient awareness of, and willingness to seek, genotyping; • the willingness of healthcare providers to prescribe new therapies and the target patient population to try new therapies; • our and our partners efforts to educate healthcare providers and patients about our products; • the prevalence and severity of any side effects; • product labeling or product insert requirements of FDA, the EMA or other regulatory authorities, including any limitations or warnings contained in a product’s approved labeling; • relative convenience and ease of administration; • the strength of marketing and distribution support; • the timing of market introduction of competitive products; • adverse publicity concerning our products or competing products and treatments, including social and ethical controversies in the field of gene editing; • establishment of authorized treatment centers; • sufficient third-party payor coverage and reimbursement; and • approval of new products or technologies that are more favorably received than our products, are more cost effective or render our products obsolete.
See, for example, “Risk Factors —Risks Related to Intellectual Property— Third-party Claims Of Overlapping Intellectual Property Rights May Prevent Or Delay Our Product Discovery and Development Efforts.” Such challenges may result in loss of patent rights, loss of exclusivity or freedom to operate, or in patent claims being narrowed, revoked, withdrawn, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and product candidates.
See, for example, “Risk Factors —Risks Related to Intellectual Property— Third-party Claims Of Overlapping Intellectual Property Rights May Prevent Or Delay Our 73 Product Discovery and Development Efforts.” Such challenges may result in loss of patent rights, loss of exclusivity or freedom to operate, or in patent claims being narrowed, revoked, withdrawn, invalidated or held unenforceable, in whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and product candidates.
For additional information regarding the manufacture of CASGEVY, please see “ Risk Factors—Risks Related to Our Relationships with Third Parties—We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CAGEVY Program .” The Manufacturing Facilities For Our Product Candidates Are Subject To Rigorous Regulations And Failure To Obtain Or Maintain Regulatory Approvals Or Operate In Line With Established cGMPs And International Best Practices Could Delay Or Impair Our Ability To Commercialize Our Product Candidates.
For additional information regarding the manufacture of CASGEVY, please see “ Risk Factors—Risks Related to Our Relationships with Third Parties—We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CASGEVY Program .” The Manufacturing Facilities For Our Product Candidates Are Subject To Rigorous Regulations And Failure To Obtain Or Maintain Regulatory Approvals Or Operate In Line With Established cGMPs And International Best Practices Could Delay Or Impair Our Ability To Commercialize Our Product Candidates.
In addition to the Broad, other third parties, such as Vilnius University, ToolGen, Inc., MilliporeSigma (a subsidiary of Merck KGaA and formerly known as “Sigma-Aldrich”) and Harvard University, filed patent applications claiming CRISPR/Cas9-related inventions around or within a year after the CVC Group application was filed and allege (or may allege) that they were first to invent one or more of the inventions claimed by the CVC Group and/or claimed by Broad, i.e. before the CVC Group, before Broad, and before the other parties.
In addition to the Broad, other third parties, such as Vilnius University, ToolGen, MilliporeSigma (a subsidiary of Merck KGaA and formerly known as “Sigma-Aldrich”) and Harvard University, filed patent applications claiming CRISPR/Cas9-related inventions around or within a year after the CVC Group application was filed and allege (or may allege) that they were first to invent one or more of the inventions claimed by the CVC Group and/or claimed by Broad, i.e. before the CVC Group, before Broad, and before the other parties.
In general, the FDA requires the successful completion of two pivotal trials to support approval of a BLA, but in certain circumstances, will approve a BLA based on only one pivotal trial; and our ability to submit and obtain approval of a BLA is ultimately an FDA review decision, which will be dependent upon the data available at such time, and the available data may not be sufficiently robust from a safety and/or efficacy perspective to support the submission or approval of a BLA.
In general, the FDA requires the successful completion of two pivotal trials to support approval of a BLA, but in certain circumstances, will approve a BLA based on only one pivotal trial; and our ability to submit and obtain approval of a BLA is 53 ultimately an FDA review decision, which will be dependent upon the data available at such time, and the available data may not be sufficiently robust from a safety and/or efficacy perspective to support the submission or approval of a BLA.
These off-target cuts could lead to disruption of a gene or a genetic regulatory sequence at an unintended site in the DNA, or, in those instances where we also provide a segment of DNA to serve as a repair template, it is possible that following off-target cut events, DNA from such repair template could be integrated into the genome at an unintended site, potentially disrupting another important gene or genomic element.
These off-target cuts could lead to disruption of a gene or a genetic regulatory sequence at an unintended site in the DNA, or, in those instances where we also provide a segment of DNA to serve as a repair template, it is possible that following off-target cut events, DNA from such repair template could be integrated into the genome at an unintended site, potentially disrupting 50 another important gene or genomic element.
In addition, if our third-party contract manufacturers are unable to timely perform or become distracted as a result of actions taken by the FDA or a comparable regulatory authority, we may experience manufacturing delays or may need to find alternative manufacturing facilities, 65 which in each case, would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
In addition, if our third-party contract manufacturers are unable to timely perform or become distracted as a result of actions taken by the FDA or a comparable regulatory authority, we may experience manufacturing delays or may need to find alternative manufacturing facilities, which in each case, would significantly impact our ability to develop, obtain regulatory approval for or market our product candidates, if approved.
If we are unable to compete successfully in this highly competitive biopharmaceutical industry, our business, financial condition and results of operations could be materially adversely affected. 58 Even If We Are Able To Commercialize Any Product Candidates, Such Products May Become Subject To Unfavorable Pricing Regulations, Third-party Reimbursement Practices, Or Healthcare Reform Initiatives, Which Would Harm Our Business.
If we are unable to compete successfully in this highly competitive biopharmaceutical industry, our business, financial condition and results of operations could be materially adversely affected. Even If We Are Able To Commercialize Any Product Candidates, Such Products May Become Subject To Unfavorable Pricing Regulations, Third-party Reimbursement Practices, Or Healthcare Reform Initiatives, Which Would Harm Our Business.
If we are unable to prevent material disclosure of the non-patented intellectual property related to our technologies to third parties, and there is no guarantee that we will have any such enforceable trade secret protection, we may not be able to establish or 80 maintain a competitive advantage in our market, which could materially adversely affect our business.
If we are unable to prevent material disclosure of the non-patented intellectual property related to our technologies to third parties, and there is no guarantee that we will have any such enforceable trade secret protection, we may not be able to establish or maintain a competitive advantage in our market, which could materially adversely affect our business.
For a detailed discussion of the competition that we face with respect to our business, including our platform, product indications, other technologies (e.g. small molecule, antibody, or protein therapies), gene editing technology, gene or cell therapies, intellectual property, new technologies, personnel, clinical trial locations, reimbursement opportunities and collaborators, please see the section entitled “ Business—Competition ”.
For a detailed discussion of the competition that we face with respect to our business, 60 including our platform, product indications, other technologies (e.g. small molecule, antibody, or protein therapies), gene editing technology, gene or cell therapies, intellectual property, new technologies, personnel, clinical trial locations, reimbursement opportunities and collaborators, please see the section entitled “ Business—Competition ”.
Moreover, there is no assurance that the data obtained to date in the ongoing clinical trials of CASGEVY and being submitted or 51 planned to be submitted is or will be sufficiently robust from a safety and/or efficacy perspective to support either accelerated or conditional approval or full approval of a BLA or a foreign equivalent in all jurisdictions for which regulatory applications are submitted.
Moreover, there is no assurance that the data obtained to date in the ongoing clinical trials of CASGEVY and being submitted or planned to be submitted is or will be sufficiently robust from a safety and/or efficacy perspective to support either accelerated or conditional approval or full approval of a BLA or a foreign equivalent in all jurisdictions for which regulatory applications are submitted.
We and our CROs will be required to comply with regulations, including GCPs, for conducting, monitoring, recording and reporting the results of preclinical studies and clinical trials to ensure that the data and results are scientifically credible and accurate and that the trial patients are adequately informed, among other things, of the potential risks of participating in clinical trials and their rights are protected.
We and our CROs are and will continue to be required to comply with regulations, including GCPs, for conducting, monitoring, recording and reporting the results of preclinical studies and clinical trials to ensure that the data and results are scientifically credible and accurate and that the trial patients are adequately informed, among other things, of the potential risks of participating in clinical trials and their rights are protected.
Court of Appeals for the Federal Circuit have also narrowed patent protections and weakened 78 patent owners' rights, creating uncertainty about patent validity and enforceability. These changes, along with potential future legal developments, could weaken our ability to secure new patents or enforce existing ones. Geopolitical events can also affect patent processes.
Court of Appeals for the Federal Circuit have also narrowed patent protections and weakened patent owners' rights, creating uncertainty about patent validity and enforceability. These changes, along with potential future legal developments, could weaken our ability to secure new patents or enforce existing ones. Geopolitical events can also affect patent processes.
Although there have been significant advances in recent years in the fields of gene therapy and genome editing, including CRISPR/Cas9 gene editing technology, such technologies, including in vivo CRISPR-based genome editing technologies in particular, are relatively new and only a limited number of clinical trials of product candidates based on such gene editing technologies have been commenced and their therapeutic utility is largely unproven.
Although there have been significant advances in recent years in the fields of gene therapy and genome editing, including CRISPR/Cas9 gene editing technology, such technologies, including 48 in vivo CRISPR-based genome editing technologies in particular, are relatively new and only a limited number of clinical trials of product candidates based on such gene editing technologies have been commenced and their therapeutic utility is largely unproven.
As such it is difficult to accurately predict the developmental challenges we may incur for our product candidates as they proceed through product discovery or identification, preclinical studies and clinical trials. For example, no genome editing in vivo therapy has been approved in the United States, EU or other key jurisdictions.
As such it is difficult to accurately predict the developmental challenges we may incur for our product candidates as they proceed through product discovery or identification, preclinical studies and clinical trials. For example, to date, no genome editing in vivo therapy has been approved in the United States, EU or other key jurisdictions.
Liabilities they incur pursuant to these laws could result in significant costs or an interruption in operations, which could have a material adverse effect on our business, financial condition, results of operations, and prospects. Risks Related to Manufacturing and Supply Gene Editing Products Are Novel And May Be Complex And Difficult To Manufacture.
Liabilities they incur pursuant to these laws could result in significant costs or an interruption in operations, which could have a material adverse effect on our business, financial condition, results of operations, and prospects. Risks Related to Manufacturing and Supply Gene Editing and Gene Silencing Products Are Novel And May Be Complex And Difficult To Manufacture.
Possible adverse side effects that could occur with treatment with gene editing products include an immunologic reaction after administration which could substantially limit the effectiveness of the treatment. 48 Immunotherapy, and its method of action of harnessing the body’s immune system, is powerful and could lead to serious side effects that we only discover in clinical trials.
Possible adverse side effects that could occur with treatment with gene editing products include an immunologic reaction after administration which could substantially limit the effectiveness of the treatment. Immunotherapy, and its method of action of harnessing the body’s immune system, is powerful and could lead to serious side effects that we only discover in clinical trials.
Accordingly, assuming we, or any collaborators we may have, receive marketing approval for one or more product candidates 56 we develop, we, and such collaborators, and our and their third-party contract manufacturers will continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance, and quality control.
Accordingly, assuming we, or any collaborators we may have, receive marketing approval for one or more product candidates we develop, we, and such collaborators, and our and their third-party contract manufacturers will continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production, product surveillance, and quality control.
In the United States, numerous states have passed comprehensive consumer privacy laws, and several other states have proposed similar legislation. The existence of comprehensive privacy laws in different states in the country would make our compliance obligations more complex and costly and may increase the likelihood that we may be subject to enforcement actions or otherwise incur liability for noncompliance.
In the United States, numerous states have passed comprehensive consumer privacy laws, and several other states have proposed similar legislation. The existence of comprehensive privacy laws in different states in the country make our compliance obligations more complex and costly and may increase the likelihood that we may be subject to enforcement actions or otherwise incur liability for noncompliance.
Moreover, our success will depend upon physicians prescribing, and their patients being willing to receive, treatments that involve the use of product candidates we may develop in lieu of, or in addition to, existing treatments with which they are already familiar and for which greater clinical data may be available.
Moreover, our success will depend upon physicians prescribing, and their patients being willing to receive, treatments that involve the use of product 57 candidates we may develop in lieu of, or in addition to, existing treatments with which they are already familiar and for which greater clinical data may be available.
Under some circumstances, the FDA, the EMA or other regulatory authorities may require that we not distribute a lot until the relevant agency authorizes its release. Slight deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls.
Under some circumstances, the FDA, the EMA or other regulatory authorities may require that we not distribute a lot until the relevant agency authorizes its release. Slight 66 deviations in the manufacturing process, including those affecting quality attributes and stability, may result in unacceptable changes in the product that could result in lot failures or product recalls.
Non-Resident Shareholders should be aware that the procedures for claiming treaty benefits (and the time required for obtaining a refund) may differ from country to country. Non-Resident Shareholders should consult their own legal, financial or tax advisors regarding receipt, ownership, purchases, sale or other dispositions of shares and the procedures for claiming a refund of the Swiss withholding tax.
Non-Resident Shareholders should be aware that the procedures for claiming treaty benefits (and the time required for obtaining a refund) may differ from country to country. Non-Resident Shareholders 85 should consult their own legal, financial or tax advisors regarding receipt, ownership, purchases, sale or other dispositions of shares and the procedures for claiming a refund of the Swiss withholding tax.
The regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as “interchangeable” based on its similarity to an approved biologic. Under the BPCIA, an application for a biosimilar product cannot 54 be approved by the FDA until 12 years after the reference product was approved under a BLA.
The regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as “interchangeable” based on its similarity to an approved biologic. Under the BPCIA, an application for a biosimilar product cannot be approved by the FDA until 12 years after the reference product was approved under a BLA.
Therefore, we cannot know with any degree of certainty whether the inventors of our patents and patent applications or our licensed patents and patent applications were the first to make the inventions claimed in our owned or any licensed patents or pending patent applications, that we were the first to file for patent protection of such inventions, or that our product candidates are not later found to infringe certain issued patents.
Therefore, we cannot know with any degree of certainty whether the inventors of our patents and patent applications or our licensed patents and patent applications were the first to make the inventions claimed in our owned or in-licensed patents or pending patent applications; that we (or our licensors) were the first to file for patent protection of such inventions, or that our product candidates are not later found to infringe certain issued patents.
In addition, payment of future 81 dividends is subject to certain limitations pursuant to Swiss law or by our articles of association. Accordingly, investors cannot rely on dividend income from our common shares and any returns on an investment in our common shares will likely depend entirely upon any future appreciation in the price of our common shares.
In addition, payment of future dividends is subject to certain limitations pursuant to Swiss law or by our articles of association. Accordingly, investors cannot rely on dividend income from our common shares and any returns on an investment in our common shares will likely depend entirely upon any future appreciation in the price of our common shares.
Our collaborators or strategic partners could develop competing products, preclude us from entering into collaborations with their competitors, fail to obtain timely regulatory approvals, terminate their agreements with us prematurely, or fail to devote sufficient resources to the development and commercialization of products. Any of these developments could harm our product development efforts.
Our 63 collaborators or strategic partners could develop competing products, preclude us from entering into collaborations with their competitors, fail to obtain timely regulatory approvals, terminate their agreements with us prematurely, or fail to devote sufficient resources to the development and commercialization of products. Any of these developments could harm our product development efforts.
Our Relationships With Healthcare Providers, Physicians, And Third-party Payors Are Subject To Applicable Anti-kickback, Fraud And Abuse And Other Healthcare Laws And Regulations, Which Could Expose Us To Criminal Sanctions, Civil Penalties, Exclusion From Government Healthcare Programs, Contractual Damages, Reputational Harm And Diminished Profits And Future Earnings.
Our Relationships With Healthcare Providers, Physicians, And Third-party Payors Are Subject To Applicable Anti-kickback, Fraud And Abuse And Other Healthcare Laws And Regulations, Which Could Expose Us To Criminal Sanctions, Civil Penalties, Exclusion From Government Healthcare Programs, Contractual Damages, Reputational Harm And Diminished Profits And Future 65 Earnings.
The loss of the services of our executive officers or other key employees or consultants could impede the achievement of our research, development 66 and commercialization objectives and seriously harm our ability to successfully implement our business strategy. If we are unable to retain high quality personnel, our ability to pursue our growth strategy will be limited.
The loss of the services of our executive officers or other key employees or consultants could impede the achievement of our research, development and commercialization objectives and seriously harm our ability to successfully implement our business strategy. If we are unable to retain high quality personnel, our ability to pursue our growth strategy will be limited.
We seek to develop, maintain and protect our proprietary position and intellectual property that is important to our business by relying upon a combination of know-how, technological innovation and intellectual property rights, including patent rights and trade secret protection, as well as entering into confidentiality agreements and in-licensing arrangements.
We seek to develop, maintain and protect our proprietary position and intellectual property that is important to our business by relying upon a combination of know-how, technological innovation and intellectual property rights, 71 including patent rights and trade secret protection, as well as entering into confidentiality agreements and in-licensing arrangements.
See, for example, “Risk Factors —Risks Related to Intellectual Property—The Intellectual Property Landscape Around Gene Editing Technology, Including CRISPR/Cas9, Is Highly Dynamic, And Third Parties May Initiate And Prevail In Legal Proceedings Alleging That The Patents That We In-License Or Own Are Invalid Or That We Are Infringing, Misappropriating, Or Otherwise Violating Their Intellectual Property Rights, The Outcome Of Which Would Be Uncertain And Could Have A Material Adverse Effect On The Success Of Our Business.” Consequently, we do not know whether any of our technology advances, including with respect to our gene editing platform, and product candidates will be protectable or remain protected by valid and enforceable patents.
See, for example, “Risk Factors —Risks Related to Intellectual Property—The Intellectual Property Landscape Around Gene Editing Technology, Including CRISPR/Cas9, Is Highly Dynamic, And Third Parties May Initiate And Prevail In Legal Proceedings Alleging That The Patents That We In-License Or Own Are Invalid Or That We Are Infringing, Misappropriating, Or Otherwise Violating Their Intellectual Property Rights, The Outcome Of Which Would Be Uncertain And Could Have A Material Adverse Effect On The Success Of Our Business.” Consequently, we do not know whether any of our technology advances or novel discoveries, including with respect to our gene editing platform, and product candidates will be protectable or remain protected by valid and enforceable patents.
If any of our trade secrets or proprietary information were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with us.
If any of our trade secrets or proprietary information were to be lawfully obtained or independently developed by a competitor or other third party, we would have no right to prevent them, or those to whom 82 they communicate it, from using that technology or information to compete with us.
We currently generate no revenue from sales of any wholly-owned 44 product and we may never be able to again research, develop or commercialize a marketable product. We must file IND applications, clinical trial applications, or CTAs, or their equivalents with regulatory authorities to commence clinical trials.
We currently generate no revenue from sales of any wholly-owned product and we may never be able to again research, develop or commercialize a marketable product. We must file IND applications, clinical trial applications, or CTAs, or their equivalents with regulatory authorities to commence clinical trials.
If so designated, the FDA may expedite the development and review of any subsequent original BLA for a drug that uses or incorporates the platform technology. Even if we believe our platform technology meets the criteria for such designation, the FDA may disagree and instead determine not to grant such designation.
If so designated, the FDA may 55 expedite the development and review of any subsequent original BLA for a drug that uses or incorporates the platform technology. Even if we believe our platform technology meets the criteria for such designation, the FDA may disagree and instead determine not to grant such designation.
For additional information, see the sections entitled “Business—Coverage, Pricing and Reimbursement” and “Business—Healthcare Reform.” See also, “ Risk Factors — Risks Related to Our Relationships with Third Parties — We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CAGEVY Program. ” Risks Related to Our Relationships with Third Parties We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CASGEVY Program.
For additional information, see the sections entitled “Business—Coverage, Pricing and Reimbursement” and “Business—Healthcare Reform.” See also, “ Risk Factors — Risks Related to Our Relationships with Third Parties — We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CASGEVY Program. ” Risks Related to Our Relationships with Third Parties We Have Partnered With Vertex On Our Lead Program CASGEVY; Vertex Has Significant Control Over The CASGEVY Program.
Changes in either the patent laws or their interpretation in the United 69 States and other countries may diminish our ability to protect our intellectual property, obtain, maintain, defend and enforce our intellectual property rights and, more generally, could affect the value of our intellectual property or narrow the scope of our owned and in-licensed patents.
Changes in either the patent laws or their interpretation in the United States and other countries may diminish our ability to protect our intellectual property, obtain, maintain, defend and enforce our intellectual property rights and, more generally, could affect the value of our intellectual property or narrow the scope of our owned and in-licensed patents.
We may also 76 require licenses from third parties for certain modified or improved components of gene editing technology, such as modified nucleic acids or proteins, as well as non-CRISPR/Cas9 technologies such as delivery methods that we are evaluating for use with product candidates we may develop.
We may also require licenses from third parties for certain modified or improved components of gene editing technology, such as modified nucleic acids or proteins, as well as non-CRISPR/Cas9 technologies such as delivery methods that we are evaluating for use with product candidates we may develop.
If These Third Parties Do Not Successfully Carry Out Their Contractual Duties, Comply With Regulatory Requirements Or Meet Expected Deadlines, We May Not Be Able To Obtain Regulatory Approval For Or Commercialize Our Product Candidates And Our Business Could Be Substantially Harmed.
If These Third Parties Do Not Successfully Carry Out Their Contractual Duties, Comply With Regulatory Requirements Or Meet Expected Deadlines, We May Not Be Able To Obtain Regulatory Approval For Or Commercialize 64 Our Product Candidates And Our Business Could Be Substantially Harmed.
Our operations involve the use of hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. We contract with third parties for the disposal of these materials and wastes. We will not be able to eliminate the risk of contamination or injury from these materials.
Our operations involve the use of 69 hazardous and flammable materials, including chemicals and biological materials. Our operations also produce hazardous waste products. We contract with third parties for the disposal of these materials and wastes. We will not be able to eliminate the risk of contamination or injury from these materials.
Our partner, Vertex, generates product sales from CASGEVY, of which we receive 40% through our collaboration arrangement with Vertex. This amount is currently insufficient to cover program expenses and as such, we are responsible for 40% of losses, subject to certain limitations.
Our partner, 46 Vertex, generates product sales from CASGEVY, of which we receive 40% through our collaboration arrangement with Vertex. This amount is currently insufficient to cover program expenses and as such, we are responsible for 40% of losses, subject to certain limitations.
In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that such 52 product candidates no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.
In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that such product candidates no longer meet the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.
We May Not Be Able To Protect Our Intellectual Property And Proprietary Rights Throughout The World. Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly in developing countries.
We May Not Be Able To Protect Our Intellectual Property And Proprietary Rights Throughout The World. 79 Filing, prosecuting and defending patents on our product candidates in all countries throughout the world would be prohibitively expensive. The requirements for patentability may differ in certain countries, particularly in developing countries.
Interim, top-line and preliminary data remain subject to audit and verification procedures that may result in the final data being materially 50 different from the preliminary data we previously announced. As a result, preliminary, interim and top-line data should be viewed with caution until the final data are available.
Interim, top-line and preliminary data remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously announced. As a result, preliminary, interim and top-line data should be viewed with caution until the final data are available.
We will face an inherent risk of product liability exposure related to the testing of our product candidates in human clinical trials 67 and will face an even greater risk of claims and litigation relating to our products if and when we commercially sell any product candidates that we may develop.
We will face an inherent risk of product liability exposure related to the testing of our product candidates in human clinical trials and will face an even greater risk of claims and litigation relating to our products if and when we commercially sell any product candidates that we may develop.
The FDA also may place other conditions on approvals including the requirement for a REMS to assure the safe use of the product. If the FDA concludes a REMS is needed, the sponsor of the BLA, must submit a proposed REMS before it can obtain approval.
The FDA also may place other conditions on approvals including the requirement for a REMS to assure the safe use of the product. If the FDA concludes a REMS is 58 needed, the sponsor of the BLA, must submit a proposed REMS before it can obtain approval.
As a result, we do not control the timing of and completion of IND and BLA filings or other applicable regulatory or required pricing approvals, including foreign equivalents, for the product candidates, including CASGEVY, under the Amended A&R Vertex JDCA.
As a result, we do not control the timing of and completion of IND and BLA filings or other applicable regulatory or required pricing approvals, including foreign equivalents, for the product candidates, including CASGEVY, 61 under the Amended A&R Vertex JDCA.
For example, the manufacture of cell and genetic therapies requires significant expertise, and even with the relevant experience and expertise, manufacturers of cell and genetic therapy products often encounter difficulties in production, including difficulties with production costs and yields, quality control, and 59 compliance with federal, state and foreign regulations.
For example, the manufacture of cell and genetic therapies requires significant expertise, and even with the relevant experience and expertise, manufacturers of cell and genetic therapy products often encounter difficulties in production, including difficulties with production costs and yields, quality control, and compliance with federal, state and foreign regulations.
If we or our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and FDA or comparable regulatory 62 authorities may require us to perform additional clinical trials before approving our marketing applications.
If we or our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and FDA or comparable regulatory authorities may require us to perform additional clinical trials before approving our marketing applications.
We also rely on trade secret protection and confidentiality agreements to maintain our competitive position and to protect our technology, unpatented proprietary know-how, including processes for which patents are difficult to enforce, as well as other proprietary and confidential information.
We also rely on trade secret protection and confidentiality agreements to maintain our competitive position and to protect our technology, unpatented proprietary know-how, including processes for which patents are difficult to enforce, as well as other 72 proprietary and confidential information.
We May Be Subject To Claims That Our Employees, Consultants, Or Advisors Have Wrongfully Used Or Disclosed Confidential Information Of Their Current Or Former Employers Or Other Third Parties Or Claims Asserting Ownership Of What We Regard As Our Own Intellectual Property.
We May Be Subject To Claims That Our Employees, Consultants, Or Advisors Have Wrongfully Used Or Disclosed Confidential Information Of Their Current Or Former Employers Or Other Third Parties Or Claims Asserting Ownership Of What 81 We Regard As Our Own Intellectual Property.
Our platform and product focus is on the development of therapies using gene editing technology, including CRISPR/Cas9, as well as other next-generation editing technologies for targeted gene correction and gene insertion with non-viral delivery approaches.
Our platform and product focus is on the development of therapies using gene-based technology, including CRISPR/Cas9, as well as other technologies, including next-generation editing technologies for targeted gene correction and gene insertion with non-viral delivery approaches.
Furthermore, publications of 72 discoveries in the scientific literature often lag behind the actual discoveries and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all.
Furthermore, publications of discoveries in the scientific literature often lag behind the actual discoveries and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all.
More restrictive government regulations or negative public opinion would have a negative effect on our business or 55 financial condition and may delay or impair our development and commercialization of product candidates or demand for any products we may develop.
More restrictive government regulations or negative public opinion would have a negative effect on our business or financial condition and may delay or impair our development and commercialization of product candidates or demand for any products we may develop.
In addition, any such changes do not guarantee that we will be effective in maintaining the adequacy of our internal controls, 68 and any failure to maintain that adequacy could prevent us from accurately reporting our financial results.
In addition, any such changes do not guarantee that we will be effective in maintaining the adequacy of our internal controls, and any failure to maintain that adequacy could prevent us from accurately reporting our financial results.
Competing products, either developed by the collaborators or strategic partners or to which the collaborators or strategic partners have rights, may result in the withdrawal of partner support for our product candidates. Current or future collaborators or strategic partners could also become our competitors in the future.
Competing products, either developed by the collaborators or strategic partners or to which the collaborators or strategic partners have rights, may result in the withdrawal of partner support for our product candidates. In addition, current or future collaborators or strategic partners could also become our competitors in the future.
General Risks We Incur Significant Costs As A Result Of Operating As A Public Company And Our Management Is Required To Devote Substantial Time To Compliance Initiatives And Corporate Governance Practices. 87 As a public company, we incur significant legal, accounting and other expenses.
General Risks We Incur Significant Costs As A Result Of Operating As A Public Company And Our Management Is Required To Devote Substantial Time To Compliance Initiatives And Corporate Governance Practices. As a public company, we incur significant legal, accounting and other expenses.
If one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception in the business and financial communities could be adversely affected.
If one of our collaborators terminates its agreement with us, we may find it more difficult to attract new collaborators and our perception and reputation in the business and financial communities could be adversely affected.
See, for example, " Risk Factors--Risks Related to Manufacturing--We Expect To Rely On Third Parties To Manufacture Our Clinical Product Supplies, And We Intend To Rely On Third Parties For At Least A Portion Of The Manufacturing Process Of Our Product Candidates.
See, for example, “ Risk Factors--Risks Related to Manufacturing--We Expect To Rely On Third Parties To Manufacture Our Clinical Product Supplies, And We Intend To Rely On Third Parties For At Least A Portion Of The Manufacturing Process Of Our Product Candidates.
For some of our product candidates, we may decide to collaborate with additional 61 pharmaceutical and biotechnology companies for the development and potential commercialization of those product candidates. We face significant competition in seeking appropriate collaborators.
For some of our product candidates, we may decide to collaborate with additional pharmaceutical and biotechnology companies for the development and potential commercialization of those product candidates. We face significant competition in seeking appropriate collaborators.
Interference or derivation proceedings provoked by third parties or brought by the USPTO may be necessary to determine the priority of inventions with respect to, or the correct inventorship of, our patents or patent applications or those of our licensors.
Interference or derivation proceedings provoked by third parties or brought by the USPTO may be necessary to determine the priority of inventions with respect to, or the correct inventorship of, our patents or patent applications or those of our 75 licensors.
There can be no assurance that we will be able to successfully complete such negotiations and ultimately acquire the rights to the intellectual property surrounding the additional product candidates or technology that we may seek to acquire.
There can be no assurance that we will be able to successfully complete such negotiations and ultimately acquire the rights to the intellectual property surrounding the additional product candidates or technology 78 that we may seek to acquire.
We license the intellectual property that covers certain of our platform gene editing technology from a third party, and we expect to continue to in-license additional third-party intellectual property rights as we expand our gene editing and other technology.
We license the intellectual property that covers certain parts of our platform gene editing technology from a third party, and we expect to continue to in-license additional third-party intellectual property rights as we expand our gene editing and other technology.
Problems in our manufacturing process could restrict our ability to meet potential future market demand for products. 64 Our partner, Vertex, is the manufacturer and exclusive license holder of CASGEVY.
Problems in our manufacturing process could restrict our ability to meet potential future market demand for products. Our partner, Vertex, is the manufacturer and exclusive license holder of CASGEVY.
In the performance of its duties, our board of directors is required by Swiss law to consider the interests of our Company, our shareholders and our employees with due observation of the principles of reasonableness and fairness.
In the performance of its duties, our board of 83 directors is required by Swiss law to consider the interests of our Company, our shareholders and our employees with due observation of the principles of reasonableness and fairness.
Compliance with the GDPR remains a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance.
Compliance with the 87 GDPR remains a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance.
While we and our partner, Vertex, have received marketing approvals for 46 CASGEVY in certain jurisdictions, we cannot guarantee we and Vertex will receive additional marketing approvals for CASGEVY or we will receive marketing approvals for our other product candidates in the future.
While we and our partner, Vertex, have received marketing approvals for CASGEVY in certain jurisdictions, we cannot guarantee we and Vertex will receive additional marketing approvals for CASGEVY or we will receive marketing approvals for our other product candidates in the future.

… 244 more changes not shown on this page.

Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

6 edited+2 added−0 removed6 unchanged
Biggest changeAdditionally, we have implemented an employee education program that is designed to raise awareness of cybersecurity threats, including risks posed by phishing attempts. This training is included during the employee onboarding process and periodically thereafter. As part of our cybersecurity risk management program, we maintain processes to assess and review the cybersecurity practices of third-party vendors and suppliers.
Biggest changeThis training is included during the employee onboarding process and periodically thereafter. As part of our cybersecurity risk management program, we maintain processes to assess and review the cybersecurity practices of third-party vendors and suppliers. Prior to engaging third-party 93 vendors and key suppliers, we conduct a security assessment and, as appropriate, include security requirements in contracts.
We periodically engage third parties to conduct risk assessments on our systems, including penetration testing and other vulnerability analyses. Our finance department, with the assistance of outside technical advisors, periodically conducts an internal assessment of different systems to 90 assess our risk management processes, including cybersecurity risk management.
We periodically engage third parties to conduct risk assessments on our systems, including penetration testing and other vulnerability analyses. Our finance department, with the assistance of outside technical advisors, periodically conducts an internal assessment of different systems to assess our risk management processes, including cybersecurity risk management.
On an annual basis, our Head of IT provide an update to our Audit Committee regarding our cybersecurity risk management program, including as relates to critical cybersecurity risks, ongoing cybersecurity initiatives and strategies, and applicable regulatory requirements and industry standards. The Audit Committee periodically reports on cybersecurity risk management to the full board of directors.
On an annual basis, our Head of IT provides an update to our Audit Committee regarding our cybersecurity risk management program, including as it relates to critical cybersecurity risks, ongoing cybersecurity initiatives and strategies, and applicable regulatory requirements and industry standards. The Audit Committee periodically reports on cybersecurity risk management to the full board of directors.
Our board of directors has delegated to our Audit Committee oversight of our cybersecurity risk management program, including oversight of information security and cybersecurity threats and related compliance and disclosure requirements.
As part of our board of directors’ enterprise risk management program, our board of directors has responsibility for oversight of cybersecurity risk management. Our board of directors has delegated to our Audit Committee oversight of our cybersecurity risk management program, including oversight of information security and cybersecurity threats and related compliance and disclosure requirements.
Prior to engaging third-party vendors and key suppliers, we conduct a security assessment and, as appropriate, include security requirements in contracts. We, like other companies in our industry, face a number of cybersecurity risks in connection with our business.
We, like other companies in our industry, face a number of cybersecurity risks in connection with our business.
The Head of IT role is currently held by an individual who has over 20 years of experience with information security and business systems, including digital infrastructure and cybersecurity. As part of our board of directors’ enterprise risk management program, our board of directors has responsibility for oversight of cybersecurity risk management.
The Head of IT role is currently held by an individual with 17 years of experience leading information security, corporate systems, technology risk, and compliance management, bringing deep expertise in cybersecurity and digital infrastructure operations across diverse industries and regulatory environments.
Added
We have taken additional steps to further mature our cybersecurity monitoring and response, vulnerability management, and incident response capabilities through new vendor partnerships to centralize and develop additional detection and response capabilities.
Added
And updated comprehensive cybersecurity strategy has also been developed to guide cybersecurity risk management activities, align corporate security standards, and guide requirements for all technology across the organization with regards to cybersecurity. Additionally, we have implemented an employee education program that is designed to raise awareness of cybersecurity threats, including risks posed by phishing attempts.

Item 2. Properties

Properties — owned and leased real estate

1 edited+0 added−0 removed3 unchanged
Biggest changeThis facility is leased through March 2036 with an option to extend the term of the lease for two additional seven-year periods. We also lease laboratory and office space, for example, in San Francisco, California. We believe that our facilities are adequate for our current needs and that suitable additional or substitute space would be available if needed. 91
Biggest changeThis facility is leased through March 2036 with an option to extend the term of the lease for two additional seven-year periods. We also lease laboratory and office space, for example, in San Francisco, California. We believe that our facilities are adequate for our current needs and that suitable additional or substitute space would be available if needed.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

2 edited+1 added−0 removed1 unchanged
Biggest changeSuch proceedings may include quasi-litigation, inter partes administrative proceedings in the U.S. Patent and Trademark Office and the European Patent Office or patent offices in other countries, involving our intellectual property estate including the worldwide patent portfolio we have exclusively licensed from Dr. Charpentier. The outcome of any of the foregoing, is inherently uncertain.
Biggest changeSuch proceedings may include quasi-litigation, inter partes administrative proceedings in the U.S. Patent and Trademark Office and the European Patent Office or patent offices in other countries, involving our intellectual property estate including the worldwide patent portfolio we have exclusively licensed from Dr. Charpentier.
In addition, litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. If we were unable to prevail in any such proceedings, our business, results of operations, liquidity and financial condition could be adversely affected. Item 4. Mine Safe ty Disclosures.
In addition, litigation and related matters are costly and may divert the attention of our management and other resources that would otherwise be engaged in other activities. If we were unable to prevail in any such proceedings, our business, results of operations, liquidity and financial condition could be adversely affected. 94 Item 4. Mine Safe ty Disclosures.
Added
For example, in the fourth quarter of 2025, ToolGen, Inc., or ToolGen, initiated a lawsuit against us and other third parties alleging patent infringement by CASGEVY of a ToolGen patent relating to CRISPR/Cas9 gene editing technology. The outcome of any of the foregoing, is inherently uncertain.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

5 edited+0 added−0 removed36 unchanged
Biggest changeEACH SHAREHOLDER IS URGED TO CONSULT ITS OWN TAX ADVISOR ABOUT THE TAX CONSEQUENCES TO IT IN LIGHT OF THE SHAREHOLDER’S OWN CIRCUMSTANCES. 95 Holders As of February 7, 2025, we had approximately 17 holders of record of our common shares. This number does not include beneficial owners whose shares were held in street name.
Biggest changeEACH SHAREHOLDER IS URGED TO CONSULT ITS OWN TAX ADVISOR ABOUT THE TAX CONSEQUENCES TO IT IN LIGHT OF THE SHAREHOLDER’S OWN CIRCUMSTANCES. 98 Holders As of February 10, 2026, we had approximately 17 holders of record of our common shares. This number does not include beneficial owners whose shares were held in street name.
For Withholding Tax consequences, see above. 94 Resident Private Shareholders and Domestic Commercial Shareholders Resident Private Shareholders who receive dividends and similar cash or in-kind distributions (including liquidation proceeds as well as stock dividends or taxable repurchases of shares as described above), which are not repayments of the nominal value of the shares or qualifying additional paid-in capital, are required to report such receipts in their individual income tax returns and are subject to Swiss federal, cantonal and communal income tax on any net taxable income for the relevant tax period.
For Withholding Tax consequences, see above. 97 Resident Private Shareholders and Domestic Commercial Shareholders Resident Private Shareholders who receive dividends and similar cash or in-kind distributions (including liquidation proceeds as well as stock dividends or taxable repurchases of shares as described above), which are not repayments of the nominal value of the shares or qualifying additional paid-in capital, are required to report such receipts in their individual income tax returns and are subject to Swiss federal, cantonal and communal income tax on any net taxable income for the relevant tax period.
The Withholding Tax will also apply to payments (exceeding the respective share capital and used capital contribution reserves) upon a repurchase of shares by us, (i) if our share capital is reduced upon such repurchase (redemption of shares), (ii) if the total of 93 repurchased shares exceeds 10% of our share capital or (iii) if the repurchased shares are not resold within six years after the repurchase.
The 96 Withholding Tax will also apply to payments (exceeding the respective share capital and used capital contribution reserves) upon a repurchase of shares by us, (i) if our share capital is reduced upon such repurchase (redemption of shares), (ii) if the total of repurchased shares exceeds 10% of our share capital or (iii) if the repurchased shares are not resold within six years after the repurchase.
This graph assumes the investment of $100 on December 31, 2019 in our common shares, the Nasdaq Biotechnology Index and the Nasdaq Composite Index and assumes the reinvestment of dividends, if any. The comparisons shown in the graph below are based upon historical data.
This graph assumes the investment of $100 on December 31, 2020 in our common shares, the Nasdaq Biotechnology Index and the Nasdaq Composite Index and assumes the reinvestment of dividends, if any. The comparisons shown in the graph below are based upon historical data.
The graph set forth below compares the cumulative total stockholder return on our shares between December 31, 2018 and December 31, 2024, with the cumulative total return of (a) the Nasdaq Biotechnology Index and (b) the Nasdaq Composite Index, over the same period.
The graph set forth below compares the cumulative total stockholder return on our shares between December 31, 2020 and December 31, 2025, with the cumulative total return of (a) the Nasdaq Biotechnology Index and (b) the Nasdaq Composite Index, over the same period.

Item 7. Management's Discussion & Analysis

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

62 edited+28 added−32 removed59 unchanged
Biggest changeWe have entered into a number of additional collaborations and license agreements in other therapeutic areas, including an additional agreement with Vertex for the treatment of Duchenne muscular dystrophy and myotonic dystrophy type 1, and others to support and complement our hematopoietic stem cell, CAR T, in vivo and T1D programs and platform, including agreements with: Nkarta, Inc. to develop and commercialize products leveraging donor-derived, gene-edited CAR-NK cells; Capsida Biotherapeutics, Inc. to develop in vivo gene editing therapies delivered with engineered adeno-associated virus vectors; Roswell Park Comprehensive Cancer Center to advance a gene-edited autologous CAR T program against a new target; MaxCyte, Inc. on ex vivo delivery for our hemoglobinopathy and CAR T programs; CureVac AG on optimized mRNA constructs and manufacturing for certain in vivo programs; and KSQ Therapeutics, Inc. on intellectual property for our allogeneic immuno-oncology programs. 98 Financial Overview Since our inception in October 2013, we have devoted substantially all of our resources to our research and development efforts, identifying potential product candidates, undertaking drug discovery and preclinical development activities, building and protecting our intellectual property estate, establishing internal manufacturing capabilities, organizing and staffing our company, business planning, raising capital and providing general and administrative support for these operations.
Biggest changeFinancial Overview 101 Since our inception in October 2013, we have devoted substantially all of our resources to our research and development efforts, identifying potential product candidates, undertaking drug discovery and preclinical development activities, building and protecting our intellectual property estate, establishing internal manufacturing capabilities, organizing and staffing our company, business planning, raising capital and providing general and administrative support for these operations.
We believe that our innovative research, translational expertise, and clinical development experience, position us as a leader in the development of CRISPR-based therapeutics and may enable us to create an entirely new class of highly effective and potentially curative therapies for patients with both rare and common diseases for whom current biopharmaceutical approaches have had limited success.
We believe that our innovative research, translational expertise, and clinical development experience, position us as a leader in the development of CRISPR-based therapeutics and may enable us to create an entirely new class of highly effective and potentially curative therapies for patients with both common and rare diseases for whom current biopharmaceutical approaches have had limited success.
Research and development expenses Research and development expenses consist primarily of costs incurred for our research activities, including our product discovery efforts and the development of our product candidates, which include: • employee-related expenses, including salaries, benefits and equity-based compensation expense; • costs of services performed by third parties that conduct research and development and preclinical activities on our behalf; • costs of purchasing lab supplies and non-capital equipment used in our preclinical activities and in manufacturing preclinical study materials, as well as supplies and materials used to manufacture clinical drug material; • consultant fees; • facility costs, including rent, depreciation and maintenance expenses; and • fees and other payments related to acquiring and maintaining licenses under our third-party licensing agreements.
Research and Development Expenses Research and development expenses consist primarily of costs incurred for our research activities, including our product discovery efforts and the development of our product candidates, which include: • employee-related expenses, including salaries, benefits and equity-based compensation expense; • costs of services performed by third parties that conduct research and development and preclinical and clinical activities on our behalf; • costs of purchasing lab supplies and non-capital equipment used in our preclinical activities and in manufacturing preclinical study materials, as well as supplies and materials used to manufacture clinical drug material; • consultant fees; • facility costs, including rent, depreciation and maintenance expenses; and • fees and other payments related to acquiring and maintaining licenses under certain of our third-party licensing agreements.
This is due to the numerous risks and uncertainties associated with developing such product candidates, including the uncertainty of: • successful completion of preclinical studies and IND-enabling studies; • successful enrollment in, and completion of, clinical trials; • receipt of marketing approvals from applicable regulatory authorities; • establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers; • obtaining and maintaining patent and trade secret protection and non-patent exclusivity; 99 • launching commercial sales of the product, if and when approved, whether alone or in collaboration with others; • acceptance of the product, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies and treatment options; • a continued acceptable safety profile following approval; • enforcing and defending intellectual property and proprietary rights and claims; and • achieving desirable medicinal properties for the intended indications.
This is due to the numerous risks and uncertainties associated with developing such product candidates, including the uncertainty of: • successful completion of preclinical studies and IND-enabling studies; • successful enrollment in, and completion of, clinical trials; • receipt of marketing approvals from applicable regulatory authorities; • establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers; • obtaining and maintaining patent and trade secret protection and non-patent exclusivity; • launching commercial sales of the product, if and when approved, whether alone or in collaboration with others; 102 • acceptance of the product, if and when approved, by patients, the medical community and third-party payors; • effectively competing with other therapies and treatment options; • a continued acceptable safety profile following approval; • enforcing and defending intellectual property and proprietary rights and claims; and • achieving desirable medicinal properties for the intended indications.
In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period and adjust accordingly. Recent Accounting Pronouncements Refer to Note 2 of the notes to our consolidated financial statements included in this Annual Report on Form 10-K for a discussion of recent accounting pronouncements.
In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period and adjust accordingly. Recent Accounting Pronouncements Refer to Note 2 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K for a discussion of recent accounting pronouncements.
Funding Requirements Our primary uses of capital are, and we expect will continue to be, research and development activities, manufacturing activities, compensation and related expenses, laboratory and related supplies, legal and other regulatory expenses, patent prosecution filing, defense and intellectual property maintenance costs, and general overhead costs, including costs associated with operating as a public company.
Funding Requirements Our primary uses of capital are, and we expect will continue to be, research and development activities, manufacturing activities, compensation and related expenses, laboratory and related supplies, legal and other regulatory expenses, patent prosecution filing, defense and intellectual property maintenance costs, business development activities and general overhead costs, including costs associated with operating as a public company.
CASGEVY is the first therapy to emerge from our strategic partnership with Vertex and is being advanced under a joint development and commercialization agreement between us and Vertex and certain of its affiliates. In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world.
CASGEVY is the first therapy to emerge from our strategic partnership with Vertex and is being advanced under a joint development and commercialization agreement between us and Vertex and certain of its affiliates. 99 In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world.
CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of this therapy as a potential one-time functional cure for people with severe SCD and TDT.
Overall, CASGEVY safety data presented to date is generally consistent with an autologous stem cell transplant and myeloablative conditioning. Efficacy data presented to date support the profile of this therapy as a potential one-time functional cure for people with severe SCD and TDT.
We anticipate that our expenses will increase as we continue our current research programs and development activities; seek to identify additional research programs and additional product candidates; conduct initial drug application supporting preclinical studies and initiate clinical trials for our product candidates; initiate preclinical testing and clinical trials for any other product candidates we identify and develop; seek regulatory approval for our product candidates; maintain, defend, protect and expand our intellectual property estate; further develop our gene editing platform; hire additional research, clinical and scientific personnel; incur facilities costs associated with such personnel growth; continue to develop internal manufacturing capabilities and infrastructure; and incur additional costs associated with operating as a public company.
We anticipate that our expenses will increase as we continue our current research programs and development activities; seek to identify additional research programs and additional product candidates; conduct initial drug application supporting preclinical studies and initiate clinical trials for our product candidates; pursue business development activities; initiate preclinical testing and clinical trials for any other product candidates we identify and develop; seek regulatory approval for our product candidates; maintain, defend, protect and expand our intellectual property estate; further develop our gene editing platform; hire additional research, clinical and scientific personnel; incur facilities costs associated with such personnel growth; continue to develop internal manufacturing capabilities and infrastructure; and incur additional costs associated with operating as a public company.
While our significant accounting policies are described in more detail in the notes to our financial statements included elsewhere in this Annual Report on Form 10-K, we believe that the following accounting policies are the most critical to aid you in fully understanding and evaluating our financial condition and results of operations. 100 Revenue Accounting Standards Codification Topic 606, Revenue from Contracts with Customers , or ASC 606, applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases and collaboration arrangements.
While our significant accounting policies are described in more detail in the notes to our financial statements included elsewhere in this Annual Report on Form 10-K, we believe that the following accounting policies are the most critical to aid you in fully understanding and evaluating our financial condition and results of operations. 103 Revenue Accounting Standards Codification Topic 606, Revenue from Contracts with Customers , or ASC 606, applies to all contracts with customers, except for contracts that are within the scope of other standards, such as leases and collaboration arrangements.
Amounts related to contingent milestone payments are not considered contractual obligations as they are contingent on the successful achievement of certain development, regulatory approval and commercial milestones, which may not be achieved.
Amounts related to contingent milestone payments are not considered contractual obligations as they are contingent on the successful achievement of certain development, regulatory 109 approval and commercial milestones, which may not be achieved.
Financing Activities Net cash provided by financing activities for the year ended December 31, 2024 was $332.0 million and primarily consisted of net proceeds of approximately $279.0 million from the issuance of common shares in connection with our registered direct offering, net proceeds of approximately $31.2 million from stock option exercises, and net proceeds of approximately $21.7 million from the issuance of common shares in connection with our 2021 ATM.
Net cash provided by financing activities for the year ended December 31, 2024 primarily consisted of net proceeds of approximately $279.0 million from the issuance of common shares in connection with our registered direct offering, net proceeds of approximately $31.2 million from stock option exercises, and net proceeds of approximately $21.7 million from the issuance of common shares in connection with our 2021 ATM.
We have not included these commitments on our balance sheet because the achievement and timing of these milestones is not fixed and determinable. 106
We have not included these commitments on our balance sheet because the achievement and timing of these milestones is not fixed and determinable.
In 2017, Vertex exercised its option to co-develop and co-commercialize the hemoglobinopathies program and we entered into a joint development and commercialization agreement with Vertex, which we amended and restated in 2021, pursuant to which, among other things, we are co-developing and co-commercializing CASGEVY for TDT and SCD. Diabetes .
In 2017, Vertex exercised its option to co-develop and co-commercialize the hemoglobinopathies program and we entered into a joint development and commercialization agreement with Vertex, which we amended and restated in 2021, pursuant to which, among other things, we are co-developing and co-commercializing CASGEVY for TDT and SCD. siRNA.
As a result of many factors, including those factors set forth in the "Risk Factors" section of this Annual Report on Form 10-K, our actual results could differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis. Overview Our mission is to create transformative gene-based medicines for serious human diseases.
As a result of many factors, including those factors set forth in the “Risk Factors” section of this Annual Report on Form 10-K, our actual results could differ materially from the results described in or implied by the forward-looking statements contained in the following discussion and analysis. Overview Our mission is to create transformative gene-based medicines for serious human diseases.
Accordingly, the elements of the collaboration agreements that represent activities in which both parties are active participants and to which both parties are exposed to the 101 significant risks and rewards that are dependent on the commercial success of the activities, are recorded as collaborative arrangements.
Accordingly, the elements of the collaboration agreements that represent activities in which both parties are active participants and to which both parties are exposed to the 104 significant risks and rewards that are dependent on the commercial success of the activities, are recorded as collaborative arrangements.
Any deferred amounts are only payable to Vertex as an offset against future profitability of the CAGEVY program and the amounts payable are capped at a specified maximum amount per year. Deferred costs associated with the CASGEVY program have not been recognized as of December 31, 2024 because a reasonable estimate of future payments against future profitability cannot be made.
Any deferred amounts are only payable to Vertex as an offset against future profitability of the CASGEVY program and the amounts payable are capped at a specified maximum amount per year. Deferred costs associated with the CASGEVY program have not been recognized as of December 31, 2025 because a reasonable estimate of future payments against future profitability cannot be made.
Sources of Liquidity Cash Flows Discussions of 2022 items and year-to-year comparisons between 2023 and 2022 that are not included in this Annual Report on Form 10-K can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” Part II, Item 7 of our Annual Report on Form 10-K for the fiscal year ended December 31, 2023 filed with the SEC on February 21, 2024.
Sources of Liquidity Cash Flows Discussions of 2024 items and year-to-year comparisons between 2024 and 2023 that are not included in this Annual Report on Form 10-K can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” Part II, Item 7 of our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the SEC on February 11, 2025.
Discussions of 2022 items and year-to-year comparisons between 2023 and 2022 that are not included in this Annual Report on Form 10-K can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” Part II, Item 7 of our Annual Report on Form 10-K for the fiscal year ended December 31, 2023 filed with the SEC on February 21, 2024.
Discussions of 2024 items and year-to-year comparisons between 2024 and 2023 that are not included in this Annual Report on Form 10-K can be found in “Management’s Discussion and Analysis of Financial Condition and Results of Operations” Part II, Item 7 of our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 filed with the SEC on February 11, 2025.
Collaboration revenue for the year ended December 31, 2024 was related to Vertex's achievement of a $10.0 million research milestone and $25.0 million research milestone under the Non-Ex License Agreement with Vertex in the fourth quarter of 2024.
Collaboration revenue was $35.0 million for the year ended December 31, 2024 and was related to Vertex’s achievement of a $10.0 million research milestone and $25.0 million research milestone under the Non-Ex License Agreement with Vertex in 2024.
Results of Operations The following is a discussion of the components of results of operations. This section generally discusses 2024 and 2023 items and year-to-year comparisons between 2024 and 2023.
Results of Operations The following is a discussion of the components of results of operations. This section generally discusses 2025 and 2024 items and year-to-year comparisons between 2025 and 2024.
In addition, we anticipate ongoing expenses related to the reimbursements of third-party patent related expenses in connection with certain of our in-licensed intellectual property. Collaboration expense, net Collaboration expense, net, consists of operating expenses related to the CASGEVY program under our collaboration with Vertex.
In addition, we anticipate ongoing expenses related to the reimbursements of third-party patent related expenses in connection with certain of our in-licensed intellectual property. Collaboration Expense, Net Collaboration expense, net, consists of operating expenses under our collaboration with Vertex for the hemoglobinopathies program.
We and Vertex continue to investigate CASGEVY, including (1) three clinical trials designed to assess the safety and efficacy of a single dose of CASGEVY in patients 12 to 35 years of age with severe SCD and TDT, respectively, (2) two clinical trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and (3) long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion.
We and Vertex continue to investigate CASGEVY, including in clinical trials designed to assess the safety and efficacy of a single dose of CASGEVY in patients 12 to 35 years of age with severe SCD and TDT, respectively, two pivotal trials in patients 5 to 11 years of age, one in severe SCD and a second in TDT, and long-term follow-up clinical trials designed to follow participants for up to 15 years after CASGEVY infusion.
Refer to Note 8 of the notes to our consolidated financial statements included in this Annual Report on Form 10-K for a description of revenue recognized related to Vertex. Grant Revenue Grant revenue was $2.3 million and $1.2 million, respectively, for the years ended December 31, 2024 and 2023.
Refer to Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K for a description of revenue recognized related to Vertex. Grant Revenue Grant revenue was $3.5 million and $2.3 million, respectively, for the years ended December 31, 2025 and 2024.
Revenue recognition We have not generated any revenue to date from sales of any wholly owned product. During the years ended December 31, 2024, 2023 and 2022, we recognized $35.0 million, $370.0 million and $0.4 million, respectively, of collaboration revenue, which is primarily related to our collaboration and license agreements with Vertex.
Revenue Recognition We have not generated any revenue to date from sales of any wholly-owned product. No collaboration revenue was recognized for the year ended December 31, 2025. During the years ended December 31, 2024 and 2023, we recognized $35.0 million and $370.0 million, respectively, of collaboration revenue, which is primarily related to our collaboration and license agreements with Vertex.
CAR T We believe CRISPR/Cas9 has the potential to create the next generation of CAR T cell therapies that may have a superior product profile and allow broader patient access compared to current autologous therapies.
CAR T We believe CRISPR/Cas9 has the potential to create the next generation of CAR T cell therapies that may have a superior product profile and allow broader patient access compared to current autologous therapies. We are advancing cell therapy programs for autoimmune indications and oncology.
Liquidity and Capital Resources Sources of Liquidity We have predominantly incurred losses and cumulative negative cash flows from operations since our inception. As of December 31, 2024, we had $1,903.8 million in cash, cash equivalents and marketable securities, of which approximately $53.8 million was held outside of the United States, and an accumulated deficit of $1,366.0 million.
Liquidity and Capital Resources Sources of Liquidity We have predominantly incurred losses and cumulative negative cash flows from operations since our inception. As of December 31, 2025, we had $1,975.8 million in cash, cash equivalents and marketable securities, of which approximately $103.4 million was held outside of the United States, and an accumulated deficit of $1,947.6 million.
In 2015, we partnered with Vertex and entered into a strategic collaboration, option and license agreement, which focused on the discovery and development of gene-based treatments for hemoglobinopathies and cystic fibrosis using CRISPR/Cas9 gene-editing technology.
For additional information regarding certain of these partnerships, please see “ Business—Strategic Partnerships and Collaborations .” Hemoglobinopathies. In 2015, we partnered with Vertex and entered into a strategic collaboration, option and license agreement, which focused on the discovery and development of gene-based treatments for hemoglobinopathies and cystic fibrosis using CRISPR/Cas9 gene-editing technology.
We have advanced this technology from discovery to an approved medicine with unparalleled speed, culminating in the landmark first approval of a CRISPR-based therapy, CASGEVY (exagamglogene autotemcel [exa-cel]), in 2023 with our collaborators at Vertex Pharmaceuticals Incorporated, or Vertex.
CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA. We have advanced this technology from discovery to an approved medicine with unparalleled speed, culminating in the landmark first approval of a CRISPR-based therapy, CASGEVY (exagamglogene autotemcel [exa-cel]), in 2023 with our collaborators at Vertex Pharmaceuticals Incorporated, or Vertex.
We continue to innovate on our platform to develop next-generation technologies that can enable new therapies. Through our efforts, we aim to unlock the full potential of CRISPR-based therapeutics to create medicines that can transform people's lives.
We continue to innovate on our platform to develop next-generation technologies that can enable new therapies. We are developing other technologies, including delivery technologies and other gene editing technologies, like SyNTase. Through our efforts, we aim to unlock the full potential of gene-based therapeutics to create medicines that can transform people’s lives.
Future contractual payments on operating lease and sublease obligations due within one year of December 31, 2024 are $29.4 million, and future contractual payments on operating lease and sublease obligations due greater than one year from December 31, 2024 are $265.2 million.
Future contractual payments on operating lease and sublease obligations due within one year of December 31, 2025 are $29.7 million, and future contractual payments on operating lease and sublease obligations due greater than one year from December 31, 2025 are $235.9 million.
Other income, net Other income, net, was $103.9 million for the year ended December 31, 2024, compared to $71.8 million for the year ended December 31, 2023. The increase in other income, net, was primarily due to an increase in interest income earned on cash, cash equivalents and marketable securities for the year ended December 31, 2024.
Other Income, Net Other income, net, was $86.6 million for the year ended December 31, 2025, compared to $103.9 million for the year ended December 31, 2024. The decrease in other income, net, was primarily due to a decrease in interest income earned on cash, cash equivalents and marketable securities for the year ended December 31, 2025.
To date, CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland, Kingdom of Saudi Arabia, Kingdom of 96 Bahrain and the United Arab Emirates for the treatment of eligible patients 12 years and older with SCD or TDT.
To date, CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland and certain countries in the Middle East for the treatment of eligible patients 12 years and older with SCD or TDT.
The following table provides information regarding our cash flows for each of the periods below: Years Ended December 31, 2024 2023 (in thousands) Net cash used in operating activities $ (142,774 ) $ (260,375 ) Net cash (used in) provided by investing activities (280,481 ) 374,647 Net cash provided by financing activities 331,984 62,664 Effect of exchange rate changes on cash (21 ) 73 (Decrease) increase in cash and restricted cash $ (91,292 ) $ 177,009 Operating Activities Net cash used in operating activities was $142.8 million for the year ended December 31, 2024, compared to net cash used in operating activities of $260.4 million for the year ended December 31, 2023.
The following table provides information regarding our cash flows for each of the periods below: Years Ended December 31, 2025 2024 (in thousands) Net cash used in operating activities $ (345,014 ) $ (142,774 ) Net cash used in investing activities (31,805 ) (280,481 ) Net cash provided by financing activities 426,026 331,984 Effect of exchange rate changes on cash 95 (21 ) Increase (decrease) in cash and restricted cash $ 49,302 $ (91,292 ) Operating Activities Net cash used in operating activities was $345.0 million for the year ended December 31, 2025, compared to net cash used in operating activities of $142.8 million for the year ended December 31, 2024.
An additional $0.3 million of stamp taxes related to this amount was paid in 2023. In 2024, we issued and sold 0.4 million common shares at an average price of $55.81 per share for aggregate proceeds of $21.7 million, which were net of equity issuance costs of $0.3 million.
In 2024, we issued and sold 0.4 million common shares under the 2021 ATM at an average price of $55.81 per share for aggregate proceeds of $21.7 million, which were net of equity issuance costs of $0.3 million, excluding stamp taxes of $0.2 million.
Our first in vivo programs target the liver, taking advantage of validated LNP delivery technologies, and aim to treat diseases where we can produce a strong therapeutic effect by safely disrupting a gene with well-understood genetic association.
In Vivo Liver Editing We have established a leading platform for in vivo gene editing and are rapidly advancing a pipeline of in vivo gene editing candidates that target the liver, taking advantage of validated lipid nanoparticle, or LNP, delivery technologies, and aim to treat diseases where we can produce a strong therapeutic effect by safely disrupting a gene with well-understood genetic association.
We believe that several accounting policies are important to understanding our historical and future performance. We refer to these policies as critical because these specific areas generally require us to make judgments and estimates about matters that are uncertain at the time we make the estimate, and different estimates—which also would have been reasonable—could have been used.
We refer to these policies as critical because these specific areas generally require us to make judgments and estimates about matters that are uncertain at the time we make the estimate, and different estimates—which also would have been reasonable—could have been used. On an ongoing basis, we evaluate our estimates and judgments, including those described in greater detail below.
Other income (net) Other income, net consists primarily of interest income earned on investments. Critical Accounting Policies and Significant Judgments and Estimates This discussion and analysis of our financial condition and results of operations is based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles.
Critical Accounting Policies and Significant Judgments and Estimates This discussion and analysis of our financial condition and results of operations is based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting principles. We believe that several accounting policies are important to understanding our historical and future performance.
In 2022, the sale of common shares pursuant to the 2019 Sales Agreement and the applicable prospectus supplement was not significant. In 2023, we issued and sold 0.5 million common shares at an average price of $72.32 per share for aggregate proceeds of $32.7 million, which were net of equity issuance costs of $0.4 million.
In 2023, we issued and sold 0.5 million common shares under the 2021 ATM at an average price of $72.32 per share for aggregate proceeds of $32.7 million, which were net of equity issuance costs of $0.4 million, excluding stamp taxes of $0.3 million.
Research and Development Expenses Research and development expenses were $320.7 million for the year ended December 31, 2024, compared to $387.3 million for the year ended December 31, 2023.
Research and Development Expenses Research and development expenses were $284.8 million for the year ended December 31, 2025, compared to $310.2 million for the year ended December 31, 2024.
At-the-Market Offerings In August 2019, we entered into an Open Market Sale Agreement SM with Jefferies under which we were able to offer and sell, from time to time at our sole discretion through Jefferies, as our sales agent, our common shares, par value of CHF 0.03 per share, or the August 2019 Sales Agreement.
At-the-Market Offerings (ATM) We entered into an Open Market Sale Agreement SM , or the Sales Agreement, with Jefferies LLC under which we, at our sole discretion, are able to offer and sell, from time to time at prevailing market prices, our common shares.
Most of our programs are still in early stages of development and the outcome of our efforts is uncertain, and we cannot estimate the actual amounts necessary to successfully complete the development, manufacture and commercialization of any current or future product candidates, if approved, or whether, or when, we may achieve profitability.
Most of our programs are still in early stages of research and development and the outcome of our efforts is uncertain, and we cannot estimate the actual amounts necessary to successfully complete the development, manufacture and commercialization of any current or future product candidates, if approved, or whether, or when, we may achieve profitability. 108 Until such time as we can generate substantial product revenues, if ever, we expect to finance our cash needs through a combination of equity financings, debt financings and payments received in connection with our collaboration and license agreements.
CRISPR-X While we have made significant progress with our current portfolio of programs, we recognize that we need to continue to innovate to unlock the full power of gene editing and bring potentially transformative therapies to even more patients. We have a dedicated early-stage research team called CRISPR-X that focuses on innovating next-generation editing modalities.
Next-generation Editing Modalities While we have made significant progress with our current portfolio of programs, we recognize that we may be able to bring transformative therapies to even more patients by continuing to innovate to unlock the full potential of gene editing. We are focused on innovating next-generation editing modalities.
Investing Activities Net cash used in investing activities for the year ended December 31, 2024 was $280.5 million and consisted primarily of purchases of marketable securities in excess of maturities of marketable securities of $255.4 million.
Investing Activities Net cash used in investing activities for the year ended December 31, 2025 was $31.8 million, compared to net cash used in investing of $280.5 million for the year ended December 31, 2024.
For additional information about our revenue recognition policy, see Note 2 and Note 8 of the notes to our audited consolidated financial statements included in this Annual Report on Form 10-K.
For the years ended December 31, 2025, 2024 and 2023, we generated $3.5 million, $2.3 million and $1.2 million, respectively, of grant revenue related to certain contracts with not-for-profit entities. For additional information about our revenue recognition policy, see Note 2 and Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K.
As of December 31, 2024, we have common shares having aggregate gross proceeds up to $363.7 million remaining under our current prospectus supplement, and we have issued and sold an aggregate of 1.9 million common shares at an average price of $122.73 per share for aggregate proceeds of $233.2 million, which were net of equity issuance costs of $3.1 million, excluding stamp taxes.
As of December 31, 2025, we issued and sold an aggregate of 8.0 million common shares under the 2021 ATM at an average price of $74.77 per share for aggregate proceeds of $592.2 million, which were net of equity issuance costs of $7.8 million, excluding stamp taxes of $5.9 million.
CRISPR-X is developing technologies to enable whole gene correction and insertion via non-viral DNA delivery and all-RNA systems, without requiring homology-directed repair or viral delivery of DNA. Partnerships Given the numerous potential therapeutic applications for CRISPR/Cas9, we have partnered strategically to broaden the indications we can pursue and accelerate development of programs by accessing specific technologies and/or disease-area expertise.
Partnerships Given the numerous potential therapeutic applications for CRISPR/Cas9, we have partnered strategically to broaden the indications we can pursue and accelerate development of programs by accessing specific technologies and/or disease-area expertise. We maintain broad partnerships to develop gene editing-based therapeutics in specific disease areas.
As a result, we may face difficulties raising capital through sales of our common shares or such sales may be on unfavorable terms. In 105 addition, a recession, depression or other sustained adverse market event could materially and adversely affect our business and the value of our common shares.
As a result, we may face difficulties raising capital through sales of our common shares or such sales may be on unfavorable terms.
Net cash provided by financing activities for the year ended December 31, 2023 was $62.7 million and consisted of net proceeds of $32.7 million from the issuance of common shares and net proceeds of approximately $29.9 million from stock option exercises.
Net cash provided by financing activities for the year ended December 31, 2025 consisted primarily of net proceeds of approximately $397.3 million from the sale of common shares issued in connection with our 2021 ATM and 2025 ATM, in the aggregate, as well as net proceeds of approximately $27.7 million from stock option exercise proceeds.
In 2024, 2023 and 2022, we exercised our option to defer specified costs on the CASGEVY program in excess of the deferral limit under A&R Vertex JDCA, as amended, resulting in deferred costs of $102.8 million, $80.9 million and $36.1 million, respectively.
In 2024, we exercised our option to defer specified costs under the CASGEVY program in excess of the $110.3 million deferral limit under the A&R Vertex JDCA, as amended. The increase of approximately $92.8 million in collaboration expense, net, was primarily attributable to reaching the deferral limit in 2024, as no such limit was applicable in 2025.
It is being investigated in an ongoing clinical trial designed to assess the safety and efficacy of the product candidate in adult patients with relapsed or refractory B-cell malignancies who have received at least two prior lines of therapy, as well as an ongoing clinical trial in adult patients with systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis.
Zugo-cel continues to advance in both autoimmune disease and hematologic malignancies. 100 In autoimmune disease, it is being investigated in an ongoing clinical trial designed to assess the safety and efficacy of the product candidate in adult patients with systemic lupus erythematosus, or SLE, systemic sclerosis, and inflammatory myositis, and a second clinical trial in immune thrombocytopenia purpura and warm autoimmune hemolytic anemia.
We have established a portfolio of therapeutic programs spanning four core franchises: hemoglobinopathies, CAR T, in vivo approaches and type 1 diabetes.
We are a leading biopharmaceutical company focused on the development of CRISPR-based therapeutics, including by using CRISPR/Cas9 technology. We have established a portfolio of therapeutic programs spanning four core franchises: hemoglobinopathies, in vivo approaches, CAR T, and regenerative medicine.
CTX310 is being investigated in an ongoing clinical trial targeting ANGPTL3 in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia.
Our in vivo portfolio includes cardiovascular programs, such as CTX310, directed towards angiopoietin-related protein 3 or ANGPTL3, which is currently in an ongoing Phase 1b clinical trial in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia.
Under the A&R Vertex JDCA, as amended, we have an option to defer our portion of specified costs on the CASGEVY program in excess of $110.3 million for the years ended December 31, 2022, 2023 and 2024.
Other obligations Under the A&R Vertex JDCA, as amended, for 2022, 2023 and 2024, the Company had an option to defer a portion of its share of costs if spending on the CASGEVY program exceeded specified amounts, which the Company exercised in each such year, resulting in deferred costs of $221.8 million, in the aggregate.
Additional Financings In February 2024, we entered into an investment agreement for the sale of approximately $280.0 million of our common shares 104 to a group of institutional investors in a registered direct offering, at a price per share of $71.50. We received net proceeds of $279.0 million, excluding stamp taxes due of $2.8 million.
Share Issuance Agreement with Sirius Therapeutics As described in Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K, we and Sirius entered into a share issuance agreement and we registered and issued 1,842,105 common shares to Sirius, nominal value CHF 0.03 per share, at an issue price of $38.00 per share as partial consideration for entering into the Sirius Agreement. 107 Additional Financings In February 2024, we entered into an investment agreement for the sale of approximately $280.0 million of our common shares to a group of institutional investors in a registered direct offering, at a price per share of $71.50.
The following table summarizes our research and development expenses for the years ended December 31, 2024 and 2023, together with the changes in those items in dollars (in thousands): Years Ended December 31, Period to Period 2024 2023 Change External research and development expenses $ 90,614 $ 130,124 $ (39,510 ) Employee related expenses 76,029 83,316 (7,287 ) Facility expenses 98,003 105,875 (7,872 ) Stock-based compensation expenses 47,944 46,356 1,588 Other expenses 2,019 2,703 (684 ) Sublicense and license fees 6,044 18,958 (12,914 ) Total research and development expenses $ 320,653 $ 387,332 $ (66,679 ) The decrease of approximately $66.7 million was primarily attributable to the following: • $39.5 million of decreased external research and development costs, primarily associated with a decrease in variable external research and manufacturing costs; • $12.9 million of decreased sublicense and license fees, primarily attributable to a decrease in research and development licenses and milestones due to strategic partners; • $7.9 million of decreased facility expenses primarily driven by lower laboratory-related costs; and • $7.3 million of decreased employee-related expenses. 103 General and administrative expenses General and administrative expenses were $73.0 million for the year ended December 31, 2024, compared to $76.2 million for the year ended December 31, 2023.
The following table summarizes our research and development expenses for the years ended December 31, 2025 and 2024, together with the changes in those items in dollars (in thousands): Years Ended December 31, Period to Period 2025 2024 Change External research and development expenses $ 76,629 $ 80,197 $ (3,568 ) Employee related expenses 63,786 76,029 (12,243 ) Facility expenses 92,381 98,003 (5,622 ) Stock-based compensation expenses 34,374 47,944 (13,570 ) Other expenses 1,225 2,019 (794 ) Sublicense and license fees 16,411 6,044 10,367 Total research and development expenses $ 284,806 $ 310,236 $ (25,430 ) The decrease of approximately $25.4 million was primarily attributable to the following: • $25.8 million of decreased employee-related expenses, including stock-based compensation expenses, primarily driven by decreased headcount; • $5.6 million of decreased facility expenses primarily driven by lower laboratory-related costs; • $3.6 million of decreased external research and development costs, primarily associated with a decrease in variable external research and manufacturing costs; offset by • $10.4 million of increased sublicense and license fees, primarily attributable to costs incurred related to a contingent liability as of December 31, 2025, as described in Note 9 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K.
In connection with the August 2019 Sales Agreement, as amended, we have filed several prospectus supplements with the SEC to offer and sell, from time to time, common shares. We filed our current prospectus supplement for $378.6 million in August 2024.
The following are in connection with the Sales Agreement. 2021 ATM In January 2021, we filed a prospectus supplement with the SEC to offer and sell, from time to time, common shares having aggregate gross proceeds of up to $600.0 million, or, together with the subsequent prospectus supplements filed in July 2021 and August 2024 relating to the common shares remaining under the original prospectus supplement, the 2021 ATM.
Comparison of Years Ended December 31, 2024 and 2023 The following table summarizes our results of operations for the years ended December 31, 2024 and 2023, together with the dollar change in those items: 102 Years Ended December 31, Period to 2024 2023 Period Change (in thousands) Revenue: Collaboration revenue $ 35,000 $ 370,000 $ (335,000 ) Grant revenue 2,314 1,206 1,108 Total revenue 37,314 371,206 (333,892 ) Operating expenses: Research and development 320,653 387,332 (66,679 ) General and administrative 72,977 76,162 (3,185 ) Collaboration expense, net 110,250 130,250 (20,000 ) Total operating expenses 503,880 593,744 (89,864 ) Loss from operations (466,566 ) (222,538 ) (244,028 ) Other income, net 103,901 71,816 32,085 Net loss before income taxes (362,665 ) (150,722 ) (211,943 ) Provision for income taxes (3,587 ) (2,888 ) (699 ) Net loss $ (366,252 ) $ (153,610 ) $ (212,642 ) Collaboration Revenue Collaboration revenue was $35.0 million for the year ended December 31, 2024, compared to $370.0 million for the year ended December 31, 2023.
Comparison of Years Ended December 31, 2025 and 2024 The following table summarizes our results of operations for the years ended December 31, 2025 and 2024, together with the dollar change in those items: Years Ended December 31, Period to 2025 2024 Period Change (in thousands) Revenue: Collaboration revenue $ — $ 35,000 $ (35,000 ) Grant revenue 3,510 2,314 1,196 Total revenue 3,510 37,314 (33,804 ) Operating expenses: Research and development 284,806 310,236 (25,430 ) 105 Acquired in-process research and development 96,253 — 96,253 General and administrative 73,542 72,977 565 Collaboration expense, net 213,480 120,667 92,813 Total operating expenses 668,081 503,880 164,201 Loss from operations (664,571 ) (466,566 ) (198,005 ) Other income, net 86,606 103,901 (17,295 ) Net loss before income taxes (577,965 ) (362,665 ) (215,300 ) Provision for income taxes (3,634 ) (3,587 ) (47 ) Net loss $ (581,599 ) $ (366,252 ) $ (215,347 ) Collaboration Revenue No collaboration revenue was recognized for the year ended December 31, 2025.
Net cash provided by investing activities for the year ended December 31, 2023 was $374.6 million and consisted primarily of maturities of marketable securities in excess of purchases of marketable securities of $386.6 million.
The decrease in net cash used in investing activities was primarily a result of the net purchase position for marketable debt securities for the year ended December 31, 2024, compared to a net maturity position for marketable debt securities for the year ended December 31, 2025.
We have three parallel efforts to achieve this goal: (1) CTX211, an allogeneic, gene-edited, hypoimmune, stem cell derived product candidate in a device that is implanted into patients and intended to produce insulin in a glucose-dependent manner, and which is in an ongoing clinical trial; (2) CTX213, a research stage deviceless beta cell replacement product candidate consisting of unencapsulated precursor islet cells derived from edited stem cells; and (3) we have granted a non-exclusive license to certain of our CRISPR/Cas9 intellectual property to Vertex to accelerate Vertex’s development of hypoimmune cell therapies for T1D in exchange for certain milestones and royalties.
In addition, we have granted a non-exclusive license to certain of our CRISPR/Cas9 intellectual property to Vertex to accelerate Vertex’s development of hypoimmune cell therapies for T1D in exchange for certain milestones and royalties.
The decrease of $3.2 million was primarily attributable to decreased employee-related expenses and consulting and professional services-related expenses. Collaboration expense, net Collaboration expense, net, was $110.3 million for the year ended December 31, 2024, compared to $130.3 million for the year ended December 31, 2023.
General and Administrative Expenses General and administrative expenses were $73.5 million for the year ended December 31, 2025, compared to $73.0 million for the year ended December 31, 2024. 106 Collaboration Expense, Net Collaboration expense, net, was $213.5 million for the year ended December 31, 2025, compared to $120.7 million for the year ended December 31, 2024.
Refer to Note 8 of the notes to our consolidated financial statements included in this Annual Report on Form 10-K for a description of revenue recognized related to Vertex.
The $96.3 million acquired in-process research and development expense is attributable to the costs incurred upon entering the Sirius Agreement during the second quarter of 2025, as described in Note 8 of the notes to the consolidated financial statements included in this Annual Report on Form 10-K.
Removed
We are a leading gene editing company focused on the development of CRISPR-based therapeutics, including by using CRISPR/Cas9 technology. CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA. We aim to apply this technology to disrupt, delete, correct and insert genes to treat genetic diseases and to engineer advanced cellular therapies.
Added
We have established a proprietary LNP delivery platform to enable gene-editing in the liver using both CRISPR/Cas9 and our novel, proprietary SyNTase editing technologies.
Removed
We are advancing several cell therapy programs for oncology and/or autoimmune indications, including two next-generation allogeneic CAR T programs, CTX112 targeting Cluster of Differentiation 19, or CD19, and CTX131 targeting Cluster of Differentiation 70, or CD70. These product candidates incorporate edits designed to enhance CAR T potency, reduce CAR T exhaustion and evade the immune system.
Added
Additional candidates In addition, we have a number of earlier stage investigational in vivo programs leveraging gene disruption in the liver for both common and rare diseases, including CTX340, directed towards angiotensinogen for the treatment of refractory hypertension; our next-generation LPA program, CTX321 directed towards LPA , the gene encoding apolipoprotein(a), a major component of lipoprotein(a), or Lp(a), and CTX460, directed towards SERPINA1 using our proprietary SyNTase editing platform, for the treatment of alpha-1 antitrypsin deficiency.
Removed
An additional edit in CTX131 is designed to prevent CAR T cells from killing other CAR T cells. In addition, these next-generation candidates exhibit increased manufacturing robustness, with a higher and more consistent number of CAR T cells produced per batch. We are producing CTX112 and CTX131 for clinical trials at our internal GMP manufacturing facility in Framingham, Massachusetts.
Added
CTX340 and CTX321 are currently in IND-enabling studies in patients with refractory hypertension and in patients with elevated Lp(a), which has been shown to have an independent association with major adverse cardiovascular events, respectively. We are progressing CTX460 through preclinical studies.
Removed
CD19 Candidates CTX112 is being developed for both hematologic malignancies and autoimmune indications.
Added
We are also pursuing additional delivery technologies, including LNPs, for delivery to tissues beyond the liver, including hematopoietic stem cells and T cells. siRNA-based Programs Our siRNA-based portfolio includes clinical-stage programs in cardiovascular and thromboembolic diseases, developed in collaboration with Sirius Therapeutics and certain of its affiliates, or Sirius.
Removed
Early clinical studies conducted by third parties have shown that CD19-directed autologous CAR T therapy can produce long-lasting remissions in multiple autoimmune indications by deeply depleting B cells. Our first generation allogeneic CD19-directed CAR T program has demonstrated effective depletion of B cells in oncology settings, which supports the potential for CTX112 in autoimmune diseases.
Added
CTX611 (formerly known as SRSD107) is a novel double-stranded, long-acting siRNA, designed to target the human coagulation factor XI, or FXI, messenger RNA and inhibit FXI protein expression. Through modulation of the intrinsic coagulation pathway, CTX611 is intended to provide anticoagulant and antithrombotic effects.
Removed
CD70 Candidates CTX131 is being developed for both solid tumors and hematologic malignancies. It is being investigated in ongoing clinical trials designed to assess the safety and efficacy of the candidate in adult patients with relapsed or refractory solid tumors, as well as in hematologic malignancies, including, including T cell lymphomas, or TCL.
Added
Supported by clinical experience conducted by Sirius in two Phase 1 clinical trials, CTX611 is being developed as a long-acting FXI inhibitor with the potential to support infrequent, including semi-annual, subcutaneous administration. CTX611 is in an ongoing Phase 2 clinical trial in patients undergoing total knee arthroplasty.
Removed
We believe allogeneic CAR T approaches for TCL may have greater potential to meet the unmet need in this patient population given the patients’ own T cells are not suitable for autologous manufacturing. Additional candidates Our CRISPR/Cas9 platform enables us to innovate continuously by incorporating incremental edits into next-generation products.
Added
Zugocabtagene geleucel Our lead next-generation product candidate, zugocabtagene geleucel (zugo-cel; formerly CTX112), incorporates edits designed to enhance CAR T potency, reduce CAR T exhaustion and evade the immune system. As a result of the next-generation edits, zugo-cel exhibits increased manufacturing robustness, with a higher and more consistent number of CAR T cells produced per batch.
Removed
We are advancing several additional investigational CAR T programs, including an autologous, gene-edited CAR T program targeting glypican-3 for the potential treatment of solid tumors.
Added
We are producing zugo-cel for clinical trials at our internal GMP manufacturing facility in Framingham, Massachusetts.
Removed
In Vivo Our in vivo gene editing strategy focuses on gene disruption and whole gene correction – the two technologies required to address the vast majority of the most prevalent severe monogenic diseases as well as many common diseases.
Added
In oncology, the Phase 1/2 clinical trial in adult patients with relapsed or refractory B-cell malignancies who have received at least two prior lines of therapy is ongoing. Eligible disease subtypes include large B-cell lymphoma, or LBCL, follicular lymphoma grade 1-3a, marginal zone lymphoma, and mantle cell lymphoma.

… 42 more changes not shown on this page.

Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

2 edited+0 added−0 removed3 unchanged
Biggest changeInflation Inflation generally affects us by increasing our cost of labor, clinical trial and manufacturing costs. We do not believe that inflation had a material effect on our business, financial condition or results of operations during the years ended December 31, 2024, 2023 and 2022.
Biggest changeInflation Inflation generally affects us by increasing our cost of labor, clinical trial and manufacturing costs. We do not believe that inflation had a material effect on our business, financial condition or results of operations during the years ended December 31, 2025, 2024 and 2023.
Item 7A. Quantitative and Qualitati ve Disclosures About Market Risk. Interest Rate Sensitivity We are exposed to market risk related to changes in interest rates. As of December 31, 2024, we had cash, cash equivalents and marketable securities of $1,903.8 million, primarily invested in U.S.
Item 7A. Quantitative and Qualitati ve Disclosures About Market Risk. Interest Rate Sensitivity We are exposed to market risk related to changes in interest rates. As of December 31, 2025, we had cash, cash equivalents and marketable securities of $1,975.8 million, primarily invested in U.S.

Other CRSP 10-K year-over-year comparisons