10q10k10q10k.net

What changed in CRISPR Therapeutics AG's 10-K — 2023 vs 2024

vs

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

+753 added−776 removedSource: 10-K (2025-02-11) vs 10-K (2024-02-21)

Top changes in CRISPR Therapeutics AG's 2024 10-K

753 paragraphs added · 776 removed · 618 edited across 8 sections

Item 1. Business

Business — how the company describes what it does

198 edited+29 added−51 removed378 unchanged
Biggest changeThe opt-out became effective in early February 2024. The ViaCyte collaboration assets include CTX211 (formerly VCTX211), 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. We are continuing to advance a Phase 1 clinical trial for CTX211 for the treatment of T1D.
Biggest changeWe 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.
For the CRISPR THERAPEUTICS logo, we have pending applications in Canada, Germany, Korea and Switzerland, and registrations in Benelux, Brazil, Hong Kong, Italy, Japan, Mexico, Singapore, South Africa, Spain, and the UK. We have registrations for CTX112 in the EU, Switzerland, and the UK. We have registrations for CTX131 in the EU, Switzerland, and the UK.
For the CRISPR THERAPEUTICS logo, we have pending applications in Germany, Korea and Switzerland, and registrations in Benelux, Brazil, Canada, EU, Hong Kong, Italy, Japan, Mexico, Singapore, South Africa, Spain, and the UK. We have registrations for CTX112 in the EU, Switzerland, and the UK. We have registrations for CTX131 in the EU, Switzerland, and the UK.
These new technologies could have advantages over CRISPR/Cas9 gene editing in some applications and there can be no certainty that other gene editing technologies will not be considered better or more attractive than our technology for the development of products.
These new technologies could have advantages over CRISPR/Cas9 gene editing in some applications and there can be no certainty that other gene editing technologies will not be considered better or more attractive than our technology for the development of products.
Among the provisions of the ACA of importance to our potential product candidates are: • an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic products, apportioned among these entities according to their market share in certain government healthcare programs, although this fee would not apply to sales of certain products approved exclusively for orphan indications; • expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability; • expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for both branded and generic drugs and revising the definition of “average manufacturer price,” or AMP, for calculating and reporting Medicaid drug rebates on outpatient prescription drug prices and extending rebate liability to prescriptions for individuals enrolled in Medicare Advantage plans; • addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for products that are inhaled, infused, instilled, implanted or injected; • expanded the types of entities eligible for the 340B drug discount program; • established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 70% point-of-sale-discount off the negotiated price of applicable products to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient products to be covered under Medicare Part D, increased pursuant to the Bipartisan Budget Act of 2018 which became effective as of 2019; • a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and • established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription product spending.
Among the provisions of the ACA of importance to our potential product candidates are: • an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic 38 products, apportioned among these entities according to their market share in certain government healthcare programs, although this fee would not apply to sales of certain products approved exclusively for orphan indications; • expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability; • expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the minimum rebate for both branded and generic drugs and revising the definition of “average manufacturer price,” or AMP, for calculating and reporting Medicaid drug rebates on outpatient prescription drug prices and extending rebate liability to prescriptions for individuals enrolled in Medicare Advantage plans; • addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for products that are inhaled, infused, instilled, implanted or injected; • expanded the types of entities eligible for the 340B drug discount program; • established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 70% point-of-sale-discount off the negotiated price of applicable products to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient products to be covered under Medicare Part D, increased pursuant to the Bipartisan Budget Act of 2018 which became effective as of 2019; • a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and • established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription product spending.
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 39 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 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 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 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.
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; 26 • 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 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 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.
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.
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.
Cell therapies have already begun to make a meaningful impact in certain diseases and gene editing could help accelerate that progress across diverse disease areas, including oncology, autoimmune diseases and diabetes. The process of gene editing involves precisely altering DNA sequences within the genomes of cells using enzymes to cut the DNA at specific locations.
Cell therapies have already begun to make a meaningful impact in certain diseases and gene editing could help accelerate that progress across diverse disease areas, including oncology, autoimmune diseases and diabetes. 3 The process of gene editing involves precisely altering DNA sequences within the genomes of cells using enzymes to cut the DNA at specific locations.
Pediatric Studies and Exclusivity Under the Pediatric Research Equity Act of 2003 (PREA), as amended, a BLA or supplement thereto must contain data that are 32 adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
Pediatric Studies and Exclusivity Under the Pediatric Research Equity Act of 2003 (PREA), as amended, a BLA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
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.
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.
TRACR also received a non-exclusive, worldwide, royalty-free license, including the right to sublicense, to carry out internal pharmaceutical research for 23 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.
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.
The FDA and the NIH have published guidance documents with respect to the development and submission of gene therapy protocols. 28 Although the FDA has indicated that its guidance documents regarding gene therapies are not legally binding, we believe that our compliance with them is likely necessary to gain approval for any product candidate we may develop.
The FDA and the NIH have published guidance documents with respect to the development and submission of gene therapy protocols. Although the FDA has indicated that its guidance documents regarding gene therapies are not legally binding, we believe that our compliance with them is likely necessary to gain approval for any product candidate we may develop.
CTX211 benefits from work on a precursor product candidate, VCTX210, which only had four of these edits. Collectively, the edits in CTX211 improve the ability of beta cells to evade the immune system in vitro and in vivo in preclinical models, as shown below. In addition, CTX211 has been shown to reverse hyperglycemia in a diabetic rat model.
CTX211 benefits from work on a precursor product candidate, which only had four of these edits. Collectively, the edits in CTX211 improve the ability of beta cells to evade the immune system in vitro and in vivo in preclinical models, as shown below. In addition, CTX211 has been shown to reverse hyperglycemia in a diabetic rat model.
Our goal is to build a culture of diverse and passionate people striving to positively impact patients, our communities, and broader society. Our human capital resource 42 priorities include attracting, recruiting, retaining, incentivizing and integrating our existing and new employees. We believe that a diverse, equitable, and inclusive workplace allows our company to best fulfill our mission.
Our goal is to build a culture of diverse and passionate people striving to positively impact patients, our communities, and broader society. Our human capital resource priorities include attracting, recruiting, retaining, incentivizing and integrating our existing and new employees. We believe that a diverse, equitable, and inclusive workplace allows our company to best fulfill our mission.
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.
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.
On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”. This new framework 37 fundamentally changes the existing system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK.
On February 27, 2023, the UK government and the European Commission announced a political agreement in principle to replace the Northern Ireland Protocol with a new set of arrangements, known as the “Windsor Framework”. This new framework fundamentally changes the existing system under the Northern Ireland Protocol, including with respect to the regulation of medicinal products in the UK.
Mergers and acquisitions in the pharmaceutical, 25 biotechnology, and gene and cell therapy industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
Mergers and acquisitions in the pharmaceutical, biotechnology, and gene and cell therapy industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
For further information regarding risks regarding these proceedings, please see “ 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 .” 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.
Sponsors that receive a complete response letter may submit to the FDA information that represents a complete response to the issues identified by the FDA. 29 Such resubmissions are classified under PDUFA as either Class 1 or Class 2. The classification of a resubmission is based on the information submitted by an applicant in response to an action letter.
Sponsors that receive a complete response letter may submit to the FDA information that represents a complete response to the issues identified by the FDA. Such resubmissions are classified under PDUFA as either Class 1 or Class 2. The classification of a resubmission is based on the information submitted by an applicant in response to an action letter.
Data exclusivity prevents applicants for authorizations of generics or biosimilars from referencing the innovator’s preclinical and clinical data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the EU, during a period of eight years from the date on which the 35 reference product was first authorized in the EU.
Data exclusivity prevents applicants for authorizations of generics or biosimilars from referencing the innovator’s preclinical and clinical data contained in the dossier of the reference product when applying for a generic or biosimilar marketing authorization in the EU, during a period of eight years from the date on which the reference product was first authorized in the EU.
Caribou Biosciences, or Caribou, had 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, had 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 Therapeutics, has reported that it had an exclusive license to such rights from Caribou in certain fields.
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 nationally authorized product.
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.
Finally, the marketing and promotion of authorized products, including industry-sponsored continuing medical education and advertising directed toward the prescribers of 36 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. The aforementioned EU rules are generally applicable in the EEA.
The conduct of such a clinical trial could be expensive and result in delays in our commercialization efforts. In the EU, pricing and reimbursement schemes vary widely from country to country. Some countries provide that products may 38 be marketed only after a reimbursement price has been agreed.
The conduct of such a clinical trial could be expensive and result in delays in our commercialization efforts. In the EU, pricing and reimbursement schemes vary widely from country to country. Some countries provide that products may be marketed only after a reimbursement price has been agreed.
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. 1 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. In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world.
Engineered immune cell therapy is one such approach, in which immune system cells such as T cells are genetically modified to enable them to recognize and attack cancerous cells. 9 Engineered cell therapy has demonstrated encouraging results leading to multiple approvals for autologous, or patient-derived, CAR T products.
Engineered immune cell therapy is one such approach, in which immune system cells such as T cells are genetically modified to enable them to recognize and attack cancerous cells. Engineered cell therapy has demonstrated encouraging results leading to multiple approvals for autologous, or patient-derived, CAR T products.
These efforts complement other core platform capabilities, such as gRNA selection, on- and off-target assessment, multiplexing and lipid nanoparticle discovery. Other Vertex Partnered Programs 17 We have partnered with Vertex, a global leader in rare diseases, in several other disease areas beyond SCD and TDT.
These efforts complement other core platform capabilities, such as gRNA selection, on- and off-target assessment, multiplexing and lipid nanoparticle discovery. Other Vertex Partnered Programs We have partnered with Vertex, a global leader in rare diseases, in several other disease areas beyond SCD and TDT.
A product is eligible for this designation if it is a regenerative medicine therapy that is intended to treat, modify, reverse or cure a serious 30 or life-threatening disease or condition and preliminary clinical evidence indicates that the product has the potential to address unmet medical needs for such disease or condition.
A product is eligible for this designation if it is a regenerative medicine therapy that is intended to treat, modify, reverse or cure a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product has the potential to address unmet medical needs for such disease or condition.
With respect to CASGEVY only, the net profits and net losses, as applicable, incurred under the agreement through July 1, 2021 in connection with the initial shared product (i.e., CASGEVY) were shared equally between us and Vertex, and beginning July 1, 2021, 19 the net profits and net losses, as applicable, incurred under the agreement are allocated 40% to CRISPR and 60% to Vertex.
With respect to CASGEVY only, the net profits and net losses, as applicable, incurred under the agreement through July 1, 2021 in connection with the initial shared product (i.e., CASGEVY) were shared equally between us and Vertex, and beginning July 1, 2021, the net profits and net losses, as applicable, incurred under the agreement are allocated 40% to CRISPR and 60% to Vertex.
The restoration period granted on a patent covering a product is typically one-half the time between the effective date of an IND and the submission date of a marketing application, plus the time between the submission date of the marketing application and the ultimate approval date, less any time the applicant failed to 33 act with due diligence.
The restoration period granted on a patent covering a product is typically one-half the time between the effective date of an IND and the submission date of a marketing application, plus the time between the submission date of the marketing application and the ultimate approval date, less any time the applicant failed to act with due diligence.
Specifically, under the NIH Guidelines, supervision of human gene transfer trials includes evaluation and assessment by an IBC, a local institutional committee that reviews and oversees research utilizing recombinant or synthetic nucleic acid molecules at that institution.
Specifically, under the NIH Guidelines, supervision of 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.
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.
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.
Manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory 31 requirements, including cGMP regulations, which impose certain procedural and documentation requirements upon manufacturers.
Manufacturers and certain of their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP regulations, which impose certain procedural and documentation requirements upon manufacturers.
We chose to pursue this HbF upregulation strategy—rather than directly correcting the mutated beta globin gene—given the efficiency and consistency of the editing approach involved, the ability of this approach to counteract a wide variety of different beta globin mutations, including patients with TDT, and the natural history data supporting absence of symptoms in patients with HPFH. 6 Relationship between level of HbF and morbidity in sickle cell disease and beta thalassemia Patients treated with CASGEVY first undergo a treatment that mobilizes a population of HSPCs, from the bone marrow into the bloodstream.
We chose to pursue this HbF upregulation strategy—rather than directly correcting the mutated beta globin gene—given the efficiency and consistency of the editing approach involved, the ability of this approach to counteract a wide variety of different beta globin mutations, including patients with TDT, and the natural history data supporting absence of symptoms in patients with HPFH. 5 Relationship between level of HbF and morbidity in sickle cell disease and beta thalassemia Patients treated with CASGEVY first undergo a treatment that mobilizes a population of HSPCs, from the bone marrow into the bloodstream.
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 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 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.
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.
Our success will depend significantly on our ability to obtain 21 and maintain patent and other proprietary protection for our technology, our ability to defend and enforce our intellectual property rights and our ability to operate without infringing any valid and enforceable patents and proprietary rights of third parties.
Our success will depend significantly on our ability to obtain and maintain patent and other proprietary protection for our technology, our ability to defend and enforce our intellectual property rights and our ability to operate without infringing any valid and enforceable patents and proprietary rights of third parties.
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.
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.
Any of the 40 foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. Healthcare Reform A primary trend in the U.S. healthcare industry and elsewhere is cost containment.
Any of the foregoing could have a material adverse effect on our business, financial condition, results of operations and prospects. Healthcare Reform A primary trend in the U.S. healthcare industry and elsewhere is cost containment.
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.
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.
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
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
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 products.
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.
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.
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.
High 14 concentrations of Lp(a), as well as genetic variants associated with high Lp(a) concentrations, are both associated with CVD. Elevated levels of Lp(a) above 50 mg/dL are directly associated with aortic valve calcification disease, or AVCD.
High concentrations of Lp(a), as well as genetic variants associated with high Lp(a) concentrations, are both associated with CVD. Elevated levels of Lp(a) above 50 mg/dL are directly associated with aortic valve calcification disease, or AVCD.
Our international trademark estate consists of multiple pending 22 applications and registrations, including pending applications for CRISPR THERAPEUTICS standard character mark in Germany and Switzerland, and registrations in Benelux, Italy, Spain, and UK.
Our international trademark estate consists of multiple pending applications and registrations, including pending applications for CRISPR THERAPEUTICS standard character mark in Germany and Switzerland, and registrations in Benelux, Italy, Spain, and UK.
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.
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.
CRISPR-X is developing technologies to enable whole gene correction and insertion without requiring homology-directed repair, which occurs at low efficiency in many cells, or viral delivery of a DNA template, which creates toxicity risks and technical challenges. These technologies include all-RNA gene correction, non-viral delivery of DNA and novel editing and insertion techniques.
CRISPR-X is developing technologies to enable whole gene correction and insertion without requiring: (1) homology-directed repair, which occurs at low efficiency in many cells, or (2) viral delivery of a DNA template, which creates toxicity risks and technical challenges. These technologies include all-RNA gene correction, non-viral delivery of DNA and novel editing and insertion techniques.
For example, we have entered into agreements with 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 AAV vectors; Roswell Park Comprehensive Cancer Center to advance a gene-edited autologous CAR T programs against new target; MaxCyte, Inc. on ex vivo delivery for our hemoglobinopathy and immuno-oncology programs; CureVac AG on optimized mRNA constructs and manufacturing for certain in vivo programs; and KSQ Therapeutics Incorporated on intellectual property for our allogeneic immuno-oncology programs.
For example, we have entered into agreements with 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 AAV vectors; Roswell Park Comprehensive Cancer Center to advance a gene-edited autologous CAR T program against new targets; 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 Incorporated on intellectual property for our allogeneic immuno-oncology programs.
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.
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, the Patent Portfolio has named inventors who assigned their rights either to the Regents of the University of California, or California, or the University of Vienna, or Vienna. California’s rights are subject to certain overriding obligations to the sponsors of its research, including the Howard Hughes Medical Institute and the U.S. Government.
Charpentier has named inventors who assigned their rights either to the Regents of the University of California, or California, or the University of Vienna, or Vienna. California’s rights are subject to certain overriding obligations to the sponsors of its research, including the Howard Hughes Medical Institute and the U.S. Government.
Under the NIH Guidelines, recombinant and synthetic nucleic acids are defined as: (i) molecules that are constructed by joining nucleic acid molecules and that can replicate in a living cell (i.e., recombinant nucleic acids); (ii) nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules (i.e., synthetic nucleic acids); or (iii) molecules that result from the replication of those described in (i) or (ii).
Under the National Institutes of Health, or NIH, Guidelines, recombinant and synthetic nucleic acids are defined as: (i) molecules that are constructed by joining nucleic acid molecules and that can replicate in a living cell (i.e., recombinant nucleic acids); (ii) nucleic acid molecules that are chemically or by other means synthesized or amplified, including those that are chemically or otherwise modified but can base pair with naturally occurring nucleic acid molecules (i.e., synthetic nucleic acids); or (iii) molecules that result from the replication of those described in (i) or (ii).
In addition, we and Vertex entered into a non-exclusive license agreement, dated March 23, 2023, or the Non-Ex License Agreement, pursuant to which we agreed to license to Vertex, on a non-exclusive basis, certain of our gene editing intellectual property. 18 2015 Collaboration Agreement Pursuant to the 2015 Collaboration Agreement, we agreed to provide technology and options to obtain licenses relating to our CRISPR/Cas technology to Vertex in exchange for a $75.0 million upfront payment.
In addition, we and Vertex entered into a non-exclusive license agreement in March 2023, or the Non-Ex License Agreement, pursuant to which we agreed to license to Vertex, on a non-exclusive basis, certain of our gene editing intellectual property. 2015 Collaboration Agreement Pursuant to the 2015 Collaboration Agreement, we agreed to provide technology and options to obtain licenses relating to our CRISPR/Cas technology to Vertex in exchange for a $75.0 million upfront payment.
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 consumer data from minors, 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 to prevent data breaches.
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. Charpentier may terminate the license agreement immediately if TRACR challenges the enforceability, validity, or scope of any Patent Right.
TRACR 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. Charpentier may terminate the license agreement immediately if TRACR challenges the enforceability, validity, or scope of any in-licensed patent right under the TRACR License Agreement.
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, having legal bases for processing personal data relating to identifiable individuals, 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 data, 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, ensuring certain accountability measures are in place and record keeping.
The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, having legal bases and/or conditions for processing personal data, 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 data, ensuring appropriate technical and organisational measures are in place and 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, ensuring certain accountability measures are in place and record keeping.
Our first in vivo programs 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.
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.
For example, Cas9 may be determined to be less attractive than other CRISPR proteins, such as Cas12a or novel Cas enzymes that have yet to be discovered, or other CRISPR-associated nuclease variants that can edit human DNA, such as base editors and prime editors.
For example, Cas9 may be determined to be less attractive than other CRISPR proteins, such as Cas12a or novel Cas enzymes that have yet to be discovered, or other CRISPR-associated nuclease variants that can edit human DNA, such as base editors and reverse transcriptase editors.
For example, Cas9 may be determined to be less attractive than other CRISPR proteins, such as Cas12a or novel Cas enzymes that have yet to be discovered, or other CRISPR-associated nuclease variants that can edit human DNA, such as base editors and prime editors.
For example, Cas9 may be determined to be less attractive than other CRISPR proteins, such as Cas12a or novel Cas enzymes that have yet to be discovered, or other CRISPR-associated nuclease variants that can edit human DNA, such as base editors and reverse transcriptase editors.
To turn this promise into reality, we have built a broad and diversified pipeline of product candidates leveraging CRISPR/Cas9 gene editing. 5 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 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.
Enabling Technologies We have entered into a number of additional collaborations and license agreements to support and complement our ex vivo and in vivo programs, including agreements related to: technologies to deliver CRISPR/Cas9 ex vivo and in vivo ; additions to our hematopoietic stem cell and in vivo programs, including two grants to advance gene editing therapies for HIV; and enhancements to our immuno-oncology and regenerative medicine cell therapy programs and platform.
Enabling Technologies We have entered into a number of additional collaborations and license agreements to support and complement our ex vivo and in vivo programs, including agreements related to: technologies to deliver CRISPR/Cas9 ex vivo and in vivo ; additions to our hematopoietic stem cell and in vivo programs, including two grants to advance gene editing therapies for HIV; and enhancements to our CAR T and regenerative medicine cell therapy programs and platform.
While these systems were an important first step to demonstrate the potential of gene editing, their development has been challenging in practice due to the complexity of engineering protein-DNA interactions. In contrast, CRISPR/Cas9 is guided by RNA-DNA interactions, which are more predictable and straightforward to engineer and apply.
While these systems were an important first step to demonstrate the potential of gene editing, their development has been challenging in practice due to the complexity of engineering protein-DNA interactions. In contrast, CRISPR/Cas nucleases are guided by RNA-DNA interactions, which are more predictable and straightforward to engineer and apply.
While clinical trial data and information governed by HIPAA are currently exempt from the current version of the CCPA, other personal information may be applicable and possible changes to the CCPA may broaden its scope. In addition, the California Privacy Rights Act, or CPRA, imposes additional obligations on companies covered by the legislation.
While clinical trial data and information governed by HIPAA are currently exempt from the CCPA, other personal information may be applicable and possible changes to the CCPA may broaden its scope. In addition, the California Privacy Rights Act, or CPRA, amended the CCPA and imposes additional obligations on companies covered by the legislation.
D., or M.D. degrees. 355 engaged primarily in research and development or technical operations, and 52 engaged in business development, finance, information systems, facilities, human resources, legal functions, or administrative support. We consider our employee relations to be good. We are dedicated to conducting business with the highest standards of corporate responsibility.
D., or M.D. degrees, 342 engaged primarily in research and development or technical operations, and 51 engaged in business development, finance, information systems, facilities, human resources, legal functions, or administrative support. We consider our employee relations to be good. We are dedicated to conducting business with the highest standards of corporate responsibility.
In December 2023, ViaCyte elected to opt-out of the collaboration with us for the co-development and co-commercialization of gene-edited stem cell therapies for the treatment of diabetes. Per the opt-out terms, once the opt-out is complete, the on-going collaboration assets will be wholly owned by us, subject to a royalty on future sales owed to ViaCyte.
In 2023, ViaCyte elected to opt-out of the collaboration with us for the co-development and co-commercialization of gene-edited stem cell therapies for the treatment of diabetes. Per the opt-out terms, the on-going collaboration assets will be wholly owned by us, subject to a royalty on future sales owed to ViaCyte.
In addition, we have further research efforts on targeted conditioning and in vivo editing of hematopoietic stem cells that have the potential to expand the number of patients that could benefit significantly. • Immuno-oncology and autoimmune : We are progressing multiple next-generation gene-edited cell therapy programs, including allogeneic chimeric antigen receptor T cell, or CAR T, candidates for the treatment of hematological and solid tumor cancers and autoimmune diseases. • In vivo approaches : We are advancing a portfolio of programs leveraging in vivo editing for both common and rare diseases, starting with the treatment and prevention of cardiovascular disease. • Type 1 diabetes : We have multiple parallel efforts using allogeneic, gene-edited, hypoimmune, stem cell-derived beta cells to address type 1 diabetes, or T1D, without the need for chronic immunosuppression.
In addition, we have further research efforts on targeted conditioning and in vivo editing of hematopoietic stem cells that have the potential to expand the number of patients that could benefit significantly. • CAR T : We are progressing multiple next-generation gene-edited cell therapy programs, including allogeneic chimeric antigen receptor T cell, or CAR T, candidates for the treatment of hematological and solid tumor cancers and autoimmune diseases. • In vivo approaches : We are advancing a portfolio of programs leveraging in vivo editing for both common and rare diseases, including the treatment and prevention of cardiovascular disease. • Type 1 diabetes : We have multiple parallel efforts using allogeneic, gene-edited, hypoimmune, stem cell-derived beta islet cell precursors to address type 1 diabetes, or T1D, without the need for chronic immunosuppression, including both encapsulated and unencapsulated approaches.
Either party may terminate the 2019 Option Agreement upon the other party’s material breach, subject to specified notice and cure provisions.
Either party may terminate the 2019 Collaboration Agreement upon the other party’s material breach, subject to specified notice and cure provisions.
For example, Washington state recently passed a health privacy law that will regulate the collection and sharing of health information, and the law also has a private right of action, which further increases the relevant compliance risk. Connecticut and Nevada have also passed similar laws regulating consumer health data.
For example, Washington state recently enacted a health privacy law that regulates the collection and sharing of health information, and the law also has a private right of action, which further increases the relevant compliance risk. Connecticut and Nevada have also passed similar laws regulating consumer health data.
CTX112 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 CD19-positive B-cell malignancies who have received at least two prior lines of therapy.
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.
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 delivery modalities, 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 as well as our T1D program, as well as the production of various critical components, such as mRNA, we may utilize in the future.
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 (such as improvements to component systems including nucleases and single or modified gRNAs), technologies for delivering protein/nucleic acid complexes and RNA into cells (such as improved viral vector systems and self‑inactivating systems), and technology relevant to stem cell-based 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), 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.
In in vivo , these companies include Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, BioMarin Pharmaceutical, Intellia Therapeutics, Ionis Pharmaceuticals, Regeneron Pharmaceuticals and Verve Therapeutics. Gene editing is a highly active field of research and new technologies, related or unrelated to CRISPR, may be discovered and create new competition.
In in vivo , these companies include Alnylam Pharmaceuticals, Arrowhead Pharmaceuticals, Beam Therapeutics, Intellia Therapeutics, Ionis Pharmaceuticals, Prime Medicine, Regeneron Pharmaceuticals and Verve Therapeutics. Gene editing is a highly active field of research and new technologies, related or unrelated to CRISPR, may be discovered and create new competition.
Human Capital As of December 31, 2023, we had 407 full-time employees. No employees were represented by labor unions or subject to collective bargaining agreements. The majority of employees were based in Boston, Massachusetts with additional employees based in Framingham, Massachusetts, Mission Bay, California and Switzerland. 74 employees held Ph.D., Pharm.
Human Capital As of December 31, 2024, we had 393 full-time employees. No employees were represented by labor unions or subject to collective bargaining agreements. The majority of employees were based in Boston, Massachusetts with additional employees based in Framingham, Massachusetts, Mission Bay, California and Switzerland. 68 employees held Ph.D., Pharm.
We are obligated to use commercially reasonable efforts to obtain regulatory approval to market a product whose manufacture, use, sale, or importation is covered by the assigned patent rights. License Agreements CRISPR License With Dr. Charpentier In April 2014, we entered into a license agreement, or the Charpentier License Agreement, with Dr.
We are obligated to use commercially reasonable efforts to obtain regulatory approval to market a product whose manufacture, use, sale, or importation is covered by the assigned patent rights. License Agreements CRISPR License With Dr. Charpentier In April 2014, we entered into the Charpentier License Agreement with Dr. Charpentier pursuant to which we received an exclusive license under Dr.
We have entered into license agreements with Vertex with respect to cystic fibrosis, or CF, where Vertex has extensive expertise, and Duchenne muscular dystrophy, or DMD. In addition, we have entered into a collaboration agreement on myotonic dystrophy type 1, or DM1, in which we retain the option to co-develop and co-commercialize products.
We have entered into license agreements with Vertex with respect to cystic fibrosis, or CF, where Vertex has extensive expertise, and DMD. In addition, we have entered into a collaboration agreement on DM1, in which we retain the option to co-develop and co-commercialize products.
The most common treatment for beta thalassemia is chronic blood transfusions. Transfusion-dependent patients typically receive transfusions every two to four weeks and chronic administration of blood often leads to elevated levels of iron in the body, which can cause organ damage over a relatively short period of time.
Transfusion-dependent patients typically receive transfusions every two to four weeks and chronic administration of blood often leads to elevated levels of iron in the body, which can cause organ damage over a relatively short period of time.
This license is limited to therapeutic products such as pharmaceuticals and biologics and any associated companion diagnostics, for the treatment or prevention of human diseases, disorders, or conditions. For further information about this license, please see “ Business— License Agreements—CRISPR License with Dr. Charpentier .” In addition to Dr.
Charpentier is limited to therapeutic products, such as pharmaceuticals and biologics and any associated companion diagnostics, for the treatment or prevention of human diseases, disorders, or conditions. For further information about this license, please see “ Business— License Agreements—CRISPR License with Dr. Charpentier .” 19 In addition to Dr. Charpentier, the worldwide patent portfolio we have in-licensed from Dr.
We believe our gene editing capabilities have the potential to enable a beta-cell replacement product candidate that may deliver durable benefit to patients without the need for long-term immunosuppression. We have three parallel efforts to achieve this goal.
We believe our gene editing capabilities have the potential to enable a beta-cell replacement product candidate that may deliver durable benefit to patients without the need for long-term immunosuppression.
In addition, multiple groups have begun to demonstrate the utility of CAR T therapy for the treatment of various autoimmune diseases, including systemic lupus erythematosus, or SLE. Specifically, CD19-directed autologous CAR T cells have produced durable remissions in early clinical studies.
Autoimmune disease In addition, multiple groups have begun to demonstrate the utility of CAR T therapy for the treatment of various autoimmune diseases, including systemic lupus erythematosus, or SLE, progressive systemic sclerosis and idiopathic immune myositis. 8 Specifically, CD19-directed autologous CAR T cells have produced durable remissions in early clinical studies.
Non-Exclusive License Agreement In March 2023, we and Vertex entered the Non-Ex License Agreement, pursuant to which we agreed to license to Vertex, on a non-exclusive basis, 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. 20 The Non-Ex License Agreement includes, among other things, provisions relating to the following: Financial Terms .
Non-Exclusive License Agreement In March 2023, we and Vertex entered the Non-Ex License Agreement, pursuant to which we agreed to license to Vertex, on a non-exclusive basis, 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.

… 198 more changes not shown on this page.

Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

317 edited+84 added−68 removed499 unchanged
Biggest changeIf we are found to infringe a third party’s intellectual property rights, and we are unsuccessful in demonstrating that such patents are invalid or unenforceable, we could be required to obtain a license from such third party to continue developing, manufacturing, and marketing any product candidates we may develop and our technology.
Biggest changeIf we or a third party that we are obliged to defend and indemnify are found to infringe a third party’s intellectual property rights, and we are unsuccessful in demonstrating that such patents are invalid or unenforceable, we and our partners may be required to pay substantial damages, including treble damages and attorneys’ fees for willful infringement, cease commercialization of the infringing technology, including our core CRISPR/Cas9 gene editing technology, or the applicable product candidate, or we could be required to obtain one or more licenses under the applicable patents from third parties to continue developing, manufacturing, and marketing any product candidates we may develop and our gene-editing and other technologies until such patents expire or are finally determined to be held invalid or unenforceable.
Our potential product candidates, or our potential product candidates may be shown to have harmful side effects or may have other characteristics or unforeseeable consequences that may make the product candidates impractical to manufacture, unmarketable, or unlikely to receive marketing approval, or that lead to product-related claims or litigation, including without limitation personal injury/product liability claims, adverse or serious adverse events, regulatory enforcement actions, or product recalls or market withdrawals .
Our potential product candidates may be shown to have harmful side effects or may have other characteristics or unforeseeable consequences that may make the product candidates impractical to manufacture, unmarketable, or unlikely to receive marketing approval, or that lead to product-related claims or litigation, including without limitation personal injury or product liability claims, adverse or serious adverse events, regulatory enforcement actions, or product recalls or market withdrawals.
In addition, commencing any future clinical trial is also subject to acceptance by the European regulatory authorities, or its equivalent, of our CTAs, or the FDA of our INDs, and finalizing the trial design based on discussions with the applicable regulatory authorities.
In addition, commencing any future clinical trial is also subject to acceptance by the European regulatory authorities, or its equivalent, of our CTAs, or by the FDA of our INDs, and finalizing the trial design based on discussions with the applicable regulatory authorities.
Positive Results From Early Preclinical Studies Or Preliminary Results from Clinical Trials Of Our Product Candidates Are Not Necessarily Predictive Of The Results Of Later Preclinical Studies And Any Future Clinical Trials Of Our Product Candidates.
Positive Results From Early Preclinical Studies Or Preliminary Results from Clinical Trials Of Our Product Candidates Are Not Necessarily Predictive Of The Results Of Later Preclinical Or Clinical Studies And Any Future Clinical Trials Of Our Product Candidates.
We expect to rely on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, to conduct future clinical trials and we currently rely on third parties to conduct certain aspects of our preclinical studies for our product candidates.
We expect to rely on medical institutions, clinical investigators, contract laboratories and other third parties, such as CROs, to conduct future clinical trials and we currently rely on third parties to conduct certain aspects of our preclinical studies and clinical trials for our product candidates.
We are following cGMP processes necessary to release product for our clinical trials and meet all requirements from regulatory agencies, including the FDA, to allow us to support research, clinical and commercial production of our wholly-owned cell therapy product candidates and certain components thereof for certain of our programs.
We are following cGMP processes necessary to release product for certain of our clinical trials and meet all requirements from regulatory agencies, including the FDA, to allow us to support research, clinical and commercial production of our wholly-owned cell therapy product candidates and certain components thereof for certain of our programs.
In addition, the agreements under which we currently license intellectual property or technology from third parties, or maintain consents under the IMA, are complex, and certain provisions in such agreements may be susceptible to multiple interpretations, or may conflict in such a way that puts us in breach of one or more agreements, which would make us susceptible to lengthy and expensive disputes with one or more of our licensing partners or the parties to the IMA.
In addition, the agreements under which we currently in-license intellectual property or technology from third parties, or maintain consents under the IMA, are complex, and certain provisions in such agreements may be susceptible to multiple interpretations, or may conflict in such a way that puts us in breach of one or more agreements, which would make us susceptible to lengthy and expensive disputes with one or more of our licensing partners or the parties to such agreements.
Moreover, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in intellectual property laws various jurisdictions worldwide. Additionally, the patent laws of some countries do not afford intellectual property protection to the same extent as the laws of the United States.
Moreover, our ability to protect and enforce our intellectual property rights may be adversely affected by unforeseen changes in intellectual property laws in various jurisdictions worldwide. Additionally, the patent laws of some countries do not afford intellectual property protection to the same extent as the laws of the United States.
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; 89 • 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 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.
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.
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.
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 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; • contract manufacturers may not be able to execute our manufacturing procedures and other logistical support requirements appropriately; • our contract manufacturers may not perform as agreed, 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; • manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies 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 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 contract manufacturers and critical reagent suppliers may be subject to inclement weather, as well as natural or man-made disasters; • our 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 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.
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, later discovery of previously unknown problems with a product candidate, including adverse events of unanticipated severity or frequency, or with our or other collaborators’ manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: • restrictions on such products, manufacturers, or manufacturing processes; 58 • restrictions on the labeling or marketing of a product; • restrictions on the distribution or use of a product; • requirements to conduct post-marketing clinical trials; • receipt of warning or untitled letters; • restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory biologic recalls; • refusal to approve pending applications or supplements to approved applications that we or our collaborators submit; • fines, restitution, or disgorgement of profits or revenue; • suspension or withdrawal of marketing approvals or revocation of biologics licenses; • suspension of any ongoing clinical trials; • refusal to permit the import or export of our products; • product seizure or detention; and • injunctions or the imposition of civil or criminal penalties.
In addition, later discovery of previously unknown problems with a product candidate, including adverse events of unanticipated severity or frequency, or with our or other collaborators’ manufacturing processes, or failure to comply with regulatory requirements, may result in, among other things: • restrictions on such products, manufacturers, or manufacturing processes; • restrictions on the labeling or marketing of a product; • restrictions on the distribution or use of a product; • requirements to conduct post-marketing clinical trials; • receipt of warning or untitled letters; • restrictions on the marketing or manufacturing of the product, withdrawal of the product from the market, or voluntary or mandatory biologic recalls; • refusal to approve pending applications or supplements to approved applications that we or our collaborators submit; • fines, restitution, or disgorgement of profits or revenue; • suspension or withdrawal of marketing approvals or revocation of biologics licenses; • suspension of any ongoing clinical trials; • refusal to permit the import or export of our products; • product seizure or detention; and • injunctions or the imposition of civil or criminal penalties.
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.
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, (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.
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.
This statute provides in principle that a judgment rendered by a non-Swiss court may be enforced in Switzerland only if: 86 • the non-Swiss court had jurisdiction pursuant to the Swiss Federal Act on Private International Law; • the judgment of such non-Swiss court has become final and non-appealable; • the judgment does not contravene Swiss public policy; • the court procedures and the service of documents leading to the judgment were in accordance with the due process of law; and • no proceeding involving the same position and the same subject matter was first brought in Switzerland, or adjudicated in Switzerland, or was earlier adjudicated in a third state and this decision is recognizable in Switzerland.
This statute provides in principle that a judgment rendered by a non-Swiss court may be enforced in Switzerland only if: • the non-Swiss court had jurisdiction pursuant to the Swiss Federal Act on Private International Law; • the judgment of such non-Swiss court has become final and non-appealable; • the judgment does not contravene Swiss public policy; • the court procedures and the service of documents leading to the judgment were in accordance with the due process of law; and • no proceeding involving the same position and the same subject matter was first brought in Switzerland, or adjudicated in Switzerland, or was earlier adjudicated in a third state and this decision is recognizable in Switzerland.
Furthermore, if we or others later identify undesirable side effects caused by any 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 candidate; • regulatory authorities may require additional warnings on the label; • we may be required to change the way a 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; • we could be sued and held liable for harm caused to patients; and • our reputation may suffer.
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 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 in the future we are unable to demonstrate that such adverse events were caused by factors other than our product candidate or approved products, the FDA, EMA or other comparable health regulatory authorities could order us to cease further clinical studies of, or deny approval of, any product candidates we are able to develop for any or all targeted indications or cease the sale of approved products.
If in the future we are unable to demonstrate that such adverse events were caused by factors other than our product candidate or approved products, the FDA, EMA or other comparable regulatory authorities could order us to cease further clinical studies of, or deny approval of, any product candidates we are able to develop for any or all targeted indications or cease the sale of approved products.
If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay or discontinue one or more of our research or development programs or the commercialization of any product candidate, or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition and results of operations.
If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay or discontinue one or more of our research or development programs or the commercialization of any product candidate, or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial 43 condition and results of operations.
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.
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.
As explained more fully below, that leaves us in a position of holding only non-exclusive or co-exclusive rights to the patent rights that protect our core gene editing technology, and we must continue to satisfy our contractual obligations under the IMA in order to maintain the effectiveness of the consents by California and Vienna to our license from Dr. Charpentier.
As explained more fully below, that leaves us in a position of holding only non-exclusive or co-exclusive rights to the patent rights that protect our core gene editing technology, and we must continue to satisfy our contractual obligations under the IMA in order to maintain the effectiveness of the consents by California and Vienna to our license from Dr.
For example, patients who receive CASGEVY or enroll in the ongoing CASGEVY clinical trials have their own CRISPR/Cas9 edited-hematopoietic stem and progenitor cells, CASGEVY, infused back into 50 the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning.
For example, patients who receive CASGEVY or enroll in the ongoing CASGEVY clinical trials have their own CRISPR/Cas9 edited-hematopoietic stem and progenitor cells, CASGEVY, infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning.
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.
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.
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 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 Products Are Novel And May Be Complex And Difficult To Manufacture.
In addition, we may seek to obtain additional licenses from our licensors and, in connection with obtaining such licenses, we may agree to amend our existing licenses in a manner that may be more favorable to the licensors, including by agreeing to terms that could enable third 75 parties (potentially including our competitors) to receive licenses to a portion of the intellectual property that is subject to our existing licenses.
In addition, we may seek to obtain additional licenses from our licensors and, in connection with obtaining such licenses, we may agree to amend our existing licenses in a manner that may be more favorable to the licensors, including by agreeing to terms that could enable third parties (potentially including our competitors) to receive licenses to a portion of the intellectual property that is subject to our existing licenses.
For example, in March 2023, the Federal Deposit Insurance Corporation took control and was appointed receiver of Silicon Valley Bank, Signature Bank and Silvergate Capital Corp., after each bank was unable to continue their 90 operations. Since then, additional financial institutions have experienced similar failures and have been placed into receivership.
For example, in March 2023, the Federal Deposit Insurance Corporation took control and was appointed receiver of Silicon Valley Bank, Signature Bank and Silvergate Capital Corp., after each bank was unable to continue their operations. Since then, additional financial institutions have experienced similar failures and have been placed into receivership.
Under some circumstances, the FDA, the EMA or other health 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 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.
In the United States, each co-owner has the freedom to license and exploit the technology. As a result, we do not have exclusive access to any intellectual property rights that Dr. Charpentier co-owns with another entity, such as California and Vienna. Our license with Dr. Charpentier is therefore non-exclusive with respect to such co-owned rights.
Charpentier. 75 In the United States, each co-owner has the freedom to license and exploit the technology. As a result, we do not have exclusive access to any intellectual property rights that Dr. Charpentier co-owns with another entity, such as California and Vienna. Our license with Dr. Charpentier is therefore non-exclusive with respect to such co-owned rights.
As a result, we expect to continue to incur significant and increasing operating losses for the foreseeable future. Because of the numerous risks and uncertainties associated with developing gene editing product candidates, we are unable to predict the extent of any future losses or when we will become profitable, if at all.
As a result of all of the foregoing, we expect to continue to incur significant and increasing operating losses for the foreseeable future. Because of the numerous risks and uncertainties associated with developing gene editing product candidates, we are unable to predict the extent of any future losses or when we will become profitable, if at all.
Negative public reaction to gene therapy in general could result in greater government regulation and stricter labeling requirements of gene editing products, including any of our product candidates, and could cause a decrease in the demand for any products we may develop. Adverse public attitudes may adversely impact our ability to enroll 56 clinical trials.
Negative public reaction to gene therapy in general could result in greater government regulation and stricter labeling requirements of gene editing products, including any of our product candidates, and could cause a decrease in the demand for any products we may develop. Adverse public attitudes may adversely impact our ability to enroll clinical trials.
Any problems in our supply chain, manufacturing process or facilities could result in delays in planned clinical trials and increased costs, and could make 65 us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional attractive development programs.
Any problems in our supply chain, manufacturing process or facilities could result in delays in planned clinical trials and increased costs, and could make us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions, which could limit our access to additional attractive development programs.
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.
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.
As a result of these factors, it is more difficult for us to predict the time and cost of product candidate development, and we cannot predict whether the application of 48 our gene editing technology, or any similar or competitive gene editing technologies, will result in the identification, development, and regulatory approval of any products.
As a result of these factors, it is more difficult for us to predict the time and cost of product candidate development, and we cannot predict whether the application of our gene editing technology, or any similar or competitive gene editing technologies, will result in the identification, development, and regulatory approval of any products.
If any of our trade secrets 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 they communicate it, from using that technology or information to compete with us.
Freely distributable reserves are generally booked either as "statutory capital reserves" (gesetzliche Kapitalreserven, contributions received from shareholders) or in the statutory or voluntary "retained earnings.” Distributions may be made out of registered share capital—the aggregate par value of a company’s registered shares—only by way of a capital reduction.
Freely distributable reserves are generally booked either as "statutory capital reserves" ( gesetzliche Kapitalreserven, contributions received from shareholders) or in the statutory or voluntary "retained earnings." Distributions may be made out of registered share capital—the aggregate par value of a company’s registered shares—only by way of a capital reduction.
Additionally, because our technology involves gene editing across multiple cell and tissue types, we are subject to many of the challenges and risks that gene therapies face, including: • regulatory requirements and guidance governing gene and cell therapy products have changed frequently and may continue to change in the future, including, e.g., the final guidance document titled “Human Gene Therapy Products Incorporating Human Genome Editing” that the FDA issued in January 2024; 47 • to date, only a limited number of products that involve the genetic modification of patient cells have been approved in the United States and the EU; • the administration processes or related procedures for our product candidates (e.g., treatment with myeloablative busulfan conditioning prior to receiving CASGEVY or undergoing a lymphodepletion regimen prior to receiving our immunotherapy product candidates); • improper modulation of a gene sequence, including unintended editing events, insertion of a gene sequence into certain locations in a patient’s chromosome or other effects related to the technology underlying our product candidates could lead to lymphoma, leukemia or other cancers, or other aberrantly functioning cells, or other diseases, including death; • transient expression of the Cas9 protein or other genome editing components of our product candidates could lead to patients having an immunological reaction towards those cells, which could be severe or life-threatening; • corrective expression of a missing protein in patients’ cells could result in the protein being recognized as foreign, and lead to a sustained immunological reaction against the expressed protein or expressing cells, which could be severe or life-threatening; and • the FDA recommends a follow-up observation period of up to 15 years for all patients who receive treatment using gene therapies, and we may need to adopt and support, and have adopted and are supporting for certain of our trials, such an observation period for our product candidates.
Additionally, because our technology involves gene editing across multiple cell and tissue types, we are subject to many of the challenges and risks that gene therapies face, including: • regulatory requirements and guidance governing gene and cell therapy products have changed frequently and may continue to change in the future, including, e.g., the final guidance document titled “Human Gene Therapy Products Incorporating Human Genome Editing” that the FDA issued in January 2024; • to date, only a limited number of products that involve the genetic modification of patient cells have been approved in the United States, the European Union, or EU, and globally; • the administration processes or related procedures for certain of our product candidates (e.g., treatment with myeloablative busulfan conditioning prior to receiving CASGEVY or undergoing a lymphodepletion regimen prior to receiving our immunotherapy product candidates); • improper modulation of a gene sequence, including unintended editing events, insertion of a gene sequence into certain locations in a patient’s chromosome or other effects related to the technology underlying our product candidates could lead to lymphoma, leukemia or other cancers, or other aberrantly functioning cells, or other diseases, including death; • transient expression of the Cas9 protein or other genome editing components of our product candidates could lead to patients having an immunological reaction towards those cells, which could be severe or life-threatening; • corrective expression of a missing protein in patients’ cells could result in the protein being recognized as foreign, and lead to a sustained immunological reaction against the expressed protein or expressing cells, which could be severe or life-threatening; and • the FDA recommends a follow-up observation period of up to 15 years for all patients who receive treatment using gene therapies, and we may need to adopt and support, and have adopted and are supporting for certain of our trials, such an observation period for our product candidates.
However, the gene editing of our product candidates may not be successful in limiting the risk of GvHD or premature rejection by the patient. In addition, results of our immuno-oncology clinical trials could reveal a high and unacceptable severity and prevalence of side effects or unexpected characteristics.
However, the gene editing of our product candidates may not be successful in limiting the risk of GvHD or premature rejection by the patient. In addition, results of our immuno-oncology clinical trials could reveal a high and unacceptable severity and 47 prevalence of side effects or unexpected characteristics.
If we are classified as both a CFC and a passive foreign investment company, or PFIC, we generally will not be treated as a PFIC with respect to those U.S. holders that meet the definition of a Ten Percent Shareholder during the period in which we are a CFC. Certain U.S.
If we are classified as both a CFC and a passive foreign investment company, or PFIC, we generally will not be treated as a PFIC with respect to those U.S. holders that meet the definition of a Ten Percent Shareholder during the period in which we are a CFC. U.S.
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.
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.
Our Rights To Develop And Commercialize Our Technology And Product Candidates Are Subject, In Part, To The Terms And Conditions Of Licenses Granted To Us By Others. We are reliant upon licenses to certain intellectual property from third parties that are important or necessary to the development of our gene editing technology and product candidates.
Our Rights To Develop And Commercialize Our Technology And Product Candidates Are Subject, In Part, To The Terms And Conditions Of Licenses Granted To Us By Others. We are reliant upon licenses to certain intellectual property from third parties that are important or necessary to the development of our gene editing and other technology and product candidates.
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.
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.
Although we do not currently own European patents that become subject to this court's jurisdiction, our future European patents that become subject to this court's jurisdiction could present risks that might affect our business and commercialization efforts in Europe. The UPC's evolving laws may affect our ability to defend or enforce those European patents.
Although we do not currently own European patents that are subject to this court's jurisdiction, our future European patents that become subject to this court's jurisdiction could present risks that might affect our business and commercialization efforts in Europe. The UPC's evolving laws may affect our ability to defend or enforce those European patents.
If a material breach of our information technology systems or those of our vendors occurs, the market perception of the effectiveness of our security measures could be harmed and our reputation 88 and credibility could be damaged. We could be required to expend significant amounts of money and other resources to repair or replace information systems or networks.
If a material breach of our information technology systems or those of our vendors occurs, the market perception of the effectiveness of our security measures could be harmed and our reputation and credibility could be damaged. We could be required to expend significant amounts of money and other resources to repair or replace information systems or networks.
Disagreements between parties to a collaboration arrangement regarding clinical development and commercialization matters can lead to delays in the development process or commercializing the applicable product candidate and, in some cases, termination of the collaboration arrangement or result in litigation or arbitration, which would be time-consuming and expensive.
Disagreements between parties to a collaboration arrangement regarding clinical development and commercialization matters can lead to delays in the development process or commercializing the applicable product candidate and, in some cases, termination of the collaboration 60 arrangement or result in litigation or arbitration, which would be time-consuming and expensive.
For these reasons, we may encounter difficulties in the timely and accurate reporting of our financial results, which would impact our ability to provide 69 our investors with information in a timely manner. As a result, our investors could lose confidence in our reported financial information, and our stock price could decline.
For these reasons, we may encounter difficulties in the timely and accurate reporting of our financial results, which would impact our ability to provide our investors with information in a timely manner. As a result, our investors could lose confidence in our reported financial information, and our stock price could decline.
In the future, we may become party to legal matters and claims arising in the ordinary course of business, the resolution of which we do not anticipate would have a material adverse impact on our financial position, results of operations or cash flows.
In the future, we may also become party to legal matters and claims arising in the ordinary course of business, the resolution of which we do not anticipate would have a material adverse impact on our financial position, results of operations or cash flows.
Disputes may arise with the third parties from whom we license our intellectual property rights from for a variety of reasons, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • the extent to which our technology and processes infringe on, or derive from, intellectual property of the licensor that is not subject to the licensing agreement; • the sublicensing of patent and other rights under our collaborative development relationships and obligations associated with sublicensing; • our diligence obligations under the license agreement and what activities satisfy those diligence obligations; • the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and • the priority of invention of patented technology.
Disputes may arise with the third parties from whom we license our intellectual property rights from for a variety of reasons, including: • the scope of rights granted under the license agreement and other interpretation-related issues; • the extent to which our technology and processes infringe on, or derive from, intellectual property of the licensor that is not subject to a licensing agreement; • the sublicensing of patent and other rights under our collaborative development relationships and obligations associated with sublicensing; • our diligence obligations under our license and collaboration agreements and what activities satisfy those diligence obligations; • the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and • the priority of invention of patented technology.
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.
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.
If a prolonged government shutdown occurs, it could 91 significantly impact the ability of the FDA and the SEC to timely review and process our submissions, which could have a material adverse effect on our business and our timelines. Item 1B. Unresolved Staff Comments. None.
If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA and the SEC to timely review and process our submissions, which could have a material adverse effect on our business and our timelines. Item 1B. Unresolved Staff Comments. None.
The success of our product candidates will depend on several factors, including the following: • successful 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 CTAs or INDs for our product candidates to commence clinical trials; • successful enrollment in, and completion of, clinical trials and preclinical studies; • successful data from our clinical program 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 supply and commercial manufacturing and, where applicable, commercial manufacturing capabilities; • successful development of our internal manufacturing processes and transfer to larger-scale facilities operated by either a 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 the 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; • maintenance of a continued acceptable safety profile of the 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; • 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.
In general, our product candidates require preclinical and clinical development; regulatory and marketing approval in multiple jurisdictions; obtaining manufacturing supply, capacity, and expertise; building of a commercial organization; substantial investment and significant marketing efforts before we generate any revenue from product sales.
In general, our product candidates require preclinical and clinical development; regulatory and marketing approval in multiple jurisdictions; obtaining manufacturing supply, capacity, and expertise; building a commercial organization; substantial investment and significant marketing efforts before we generate any revenue from product sales.
In January 2024, the FDA determined that new safety information related to T cell malignancies should be included in the labeling with boxed warning language on these malignancies for all BCMA- and 49 CD19-directed genetically modified autologous T cell immunotherapies.
In January 2024, the FDA determined that new safety information related to T cell malignancies should be included in the labeling with boxed warning language on these malignancies for all BCMA- and CD19-directed genetically modified autologous T cell immunotherapies.
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.
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.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines, or imprisonment. Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs.
Failure to comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines, or imprisonment. Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations 63 will involve substantial costs.
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.
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.
Although the UK is regarded as a third country under the EU’s GDPR, the European Commission (“EC”) has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EEA to the UK remain unrestricted.
Although the UK is regarded as a third country under the EU’s GDPR, the European Commission has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EEA to the UK remain unrestricted.
If significant GvHD or other adverse events are observed with the administration of our product candidates, or if any of the product candidates is viewed as less safe or effective than autologous therapies or other allogenic therapies, our ability to develop allogeneic therapies may be adversely affected.
If significant GvHD or other adverse events are observed with the administration of our product candidates, or if any of the product candidates are viewed as less safe or effective than autologous therapies or other allogenic therapies, our ability to develop allogeneic therapies may be adversely affected.
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.
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.
These regulations are enforced by the FDA, the Competent Authorities of the Member States of the European Economic Area and comparable health regulatory authorities for any drugs in clinical development. The FDA enforces GCP regulations through periodic inspections of clinical trial sponsors, principal investigators and trial sites.
These regulations are enforced by the FDA, the Competent Authorities of the Member States of the European Economic Area and comparable regulatory authorities for any drugs in clinical development. The FDA enforces GCP regulations through periodic inspections of clinical trial sponsors, principal investigators and trial sites.
This provision has been transposed into the Human Medicines Regulations 2012 and so remains applicable in the UK despite its departure from the EU. 64 Payments made to physicians in certain EU Member States must be publicly disclosed.
This provision has been transposed into the Human Medicines Regulations 2012 and so remains applicable in the UK despite its departure from the EU. Payments made to physicians in certain EU Member States must be publicly disclosed.
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.
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.
Swiss resident individuals who hold their shares as private assets, or Resident Private Shareholders, are in principle eligible for a 84 full refund or credit against income tax of the Swiss withholding tax if they duly report the underlying income in their income tax return.
Swiss resident individuals who hold their shares as private assets, or Resident Private 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 tax return.
If We Cannot Replicate The Positive Results From Our Earlier Preclinical Studies Of Our Product Candidates In Our Later Preclinical Studies, Clinical Trials And Future Clinical Trials, We May Be Unable To Successfully Develop, Obtain Regulatory Approval For And Commercialize Our Product Candidates.
If We Cannot Replicate The Positive Results From Our Earlier Preclinical Or Clinical Studies Of Our Product Candidates In Our Later Preclinical Studies, Clinical Trials And Future Clinical Trials, We May Be Unable To Successfully Develop, Obtain Regulatory Approval For And Commercialize Our Product Candidates.
Moreover, preclinical, nonclinical and clinical data are often susceptible to varying 52 interpretations and analyses and many companies that believed their product candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain FDA or EMA approval.
Moreover, preclinical, nonclinical and clinical data are often susceptible to varying interpretations and analyses and many companies that believed their product candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain FDA or EMA approval.
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.
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.
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.
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.
Among other things, these provisions require the approval of at least two thirds of represented shares present or voting at a shareholder meeting for the removal of a member of our board of directors and to increase the maximum number of members of our board of directors; limit the accumulated voting rights of any person or entity to 15% of our registered share capital; limit the voting rights of an acquirer of more than 5% of our registered share capital in a transaction or series of transactions in which our board of directors did not provide for an exemption, which could prevent or delay a change in control of our Company; provide that the board of directors is authorized to conduct one or more increases of the Company’s share capital, at any time until June 8, 2028, or the expiry of the capital band, if earlier (see “ Risk Factors—Risks Related to The Ownership of Our Common Shares—Our Status As A Swiss Corporation May Limit Our Flexibility With Respect To Certain Aspects Of Capital Management And May Cause Us To Be Unable To Make Distributions Without Subjecting Our Shareholders To Swiss Withholding Tax” ), to issue a specified number of shares within the limit of the capital band, which under our current capital band is approximately sixteen percent of the share capital registered in the commercial register, and to limit or withdraw the preemptive rights of existing 83 shareholders in various circumstances; provide for a conditional share capital that authorizes the issuance of additional shares up to a maximum amount of approximately thirty-five percent of the share capital registered in the commercial register, without obtaining additional shareholder approval, (i) through the exercise of conversion and/or option rights granted in connection with bonds or similar instruments, including convertible debt instruments, and (ii) in connection with the exercise of options granted to employees or other service providers of the Company or any of its subsidiaries; and provide that a merger or demerger transaction requires the affirmative vote of at least two thirds of the shares represented at a shareholders’ meeting.
Among other things, these provisions require the approval of at least two thirds of represented shares present or voting at a shareholder meeting for the removal of a member of our board of directors and to increase the maximum number of members of our board of directors; limit the accumulated voting rights of any person or entity to 15% of our registered share capital; limit the voting rights of an acquirer of more than 5% of our registered share capital in a transaction or series of transactions in which our board of directors did not provide for an exemption, which could prevent or delay a change in control of our Company; provide that the board of directors is authorized to conduct one or more increases of the Company’s share capital, at any time until June 8, 2028, or the expiry of the capital band, if earlier (see “ Risk Factors—Risks Related to The Ownership of Our Common Shares—Our Status As A Swiss Corporation May Limit Our Flexibility With Respect To Certain Aspects Of Capital Management And May Cause Us To Be Unable To Make Distributions Without Subjecting Our Shareholders To Swiss Withholding Tax” ), to issue a specified number of shares within the limit of the capital band, which under our current capital band is approximately sixteen percent of the issued share capital, and to limit or withdraw the preemptive rights of existing shareholders in various circumstances; provide for a conditional share capital that authorizes the issuance of additional shares up to a maximum amount of approximately thirty-five percent of the issued share capital, without obtaining additional shareholder approval, (i) through the exercise of conversion and/or option rights granted in connection with bonds or similar instruments, including convertible debt instruments, and (ii) in connection with the exercise of options granted to employees or other service providers of the Company or any of its subsidiaries; and provide that a merger or demerger transaction requires the affirmative vote of at least two thirds of the shares 82 represented at a shareholders’ meeting.
If our product candidates do not achieve an adequate level 59 of acceptance following regulatory approval, if ever, we may not generate significant product revenue and may not become profitable. We Face Significant Competition In The Biotechnology And Pharmaceutical Industries.
If our product candidates do not achieve an adequate level of acceptance following regulatory approval, if ever, we may not generate significant product revenue and may not become profitable. We Face Significant Competition In The Biotechnology And Pharmaceutical Industries.
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.
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.
The facilities used to manufacture our product candidates must be evaluated by the FDA, or other health regulatory agencies in other jurisdictions, pursuant to inspections that will be conducted after we submit an application to the FDA or other health regulatory agencies.
The facilities used to manufacture our product candidates must be evaluated by the FDA, or other regulatory agencies in other jurisdictions, pursuant to inspections that will be conducted after we submit an application to the FDA or other regulatory agencies.
Risks Related to Intellectual Property If We Are Unable To Obtain Or Protect Intellectual Property Rights Related to Our Proprietary Gene Editing Technology And Product Candidates, We May Not Be Able To Compete Effectively In Our Markets.
Risks Related to Intellectual Property If We Are Unable To Obtain, Maintain Or Protect Intellectual Property Rights Related to Our Proprietary Gene Editing Technology And Product Candidates, We May Not Be Able To Compete Effectively In Our Markets.
The ultimate outcome of any pending or allowed patent application or granted patent is uncertain and the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance.
Moreover, the ultimate outcome of any pending or allowed patent application or granted patent is uncertain and the coverage claimed in a patent application can be significantly reduced before the patent is issued, and its scope can be reinterpreted after issuance.
Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for 53 each submitted product application, may cause delays in the approval or rejection of an application.
Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application.
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.
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.
Although we enter into non-disclosure and confidentiality agreements with parties who have access to confidential or patentable aspects of our research and development output, such as our employees, corporate collaborators, outside scientific collaborators, CROs, contract manufacturers, consultants advisors, and other third parties, any of these parties may breach the agreements and disclose such output before a patent application is filed, thereby jeopardizing our ability to seek patent protection.
Although we enter into non-disclosure and confidentiality agreements with parties who have access to confidential or patentable aspects of our research and development output, such as our employees, corporate collaborators, outside scientific collaborators, contract research organizations, contract manufacturers, consultants advisors, and other third parties, any of these parties may breach the agreements and disclose such output before a patent application is filed, thereby jeopardizing our ability to seek patent protection.
If passed, the final version of the Data Reform Bill may have the effect of further altering the similarities between the UK and EEA data protection regime and threaten the UK adequacy decision from the European Commission.
If passed, the final version of the UK Bill may have the effect of further altering the similarities between the UK and EEA data protection regime and threaten the UK adequacy decision from the European Commission.
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 agreements we obtain; • the extent to which we are obligated to reimburse, or entitled to reimbursement of, clinical trial costs under 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 and technologies; • the costs of establishing 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; • 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.
Even after we receive and incorporate guidance from these regulatory authorities, they could disagree that we have satisfied their requirements to commence our clinical trial or change their position on the acceptability of 46 our trial design or the clinical endpoints selected, which may require us to complete additional preclinical studies or clinical trials or impose stricter approval conditions than we currently expect.
Even after we receive and incorporate guidance from these regulatory authorities, they could disagree that we have satisfied their requirements to commence a clinical trial or change their position on the acceptability of our trial design or the clinical endpoints selected, which may require us to complete additional preclinical studies or clinical trials or impose stricter approval conditions than we currently expect.
Such a lawsuit could also divert the time and attention of our management. Unfavorable Global Economic Conditions Could Adversely Affect Our Business, Financial Condition Or Results Of Operations.
Such a lawsuit could also divert the 88 time and attention of our management. Unfavorable Global Economic Conditions Could Adversely Affect Our Business, Financial Condition Or Results Of Operations.
We are subject to and may in the future become party to, or threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our technology and any product candidates we may develop, including re-examination interference proceedings, post-grant review, inter partes review, and derivation proceedings before the USPTO and similar proceedings in other jurisdictions such as oppositions before the European Patent Office.
We are subject to and may in the future become party to, or threatened with, adversarial proceedings or litigation regarding intellectual property rights with respect to our technology and any product candidates we may develop, including re-examinations, interference proceedings, post-grant review, inter partes review, and derivation proceedings before the USPTO and similar proceedings in other jurisdictions such as oppositions before the European Patent Office.

… 389 more changes not shown on this page.

Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

5 edited+0 added−1 removed7 unchanged
Biggest changeThe 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.
Biggest changeThe 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.
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.
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.
On an annual basis, our Head of IT and vCISO 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. 92
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.
Our Chief Compliance Officer and Head of IT consult with other members of our information technology department, and with third parties with expertise in cybersecurity, including a virtual Chief Information Security Officer, or vCISO, to develop strategies to assess, address and align cybersecurity efforts with our business objectives and operational requirements.
Our Chief Compliance Officer and Head of IT consult with other members of our information technology department, and with third parties with expertise in cybersecurity, to develop strategies to assess, address and align cybersecurity efforts with our business objectives and operational requirements.
As part of our Board of Directors’, or Board’s, enterprise risk management program, our Board has responsibility for oversight of cybersecurity risk management. Our Board 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.
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.
Removed
The individual currently operating as our vCISO has over 15 years of experience in providing services as an enterprise vCISO across various industries, including life sciences and national defense and has advised various agencies of the U.S. federal government.

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.
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

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

2 edited+0 added−0 removed1 unchanged
Biggest changePatent and Trademark Office and the European Patent Office or patent offices in other countries, involving our intellectual property estate including the Patent Portfolio. 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. The outcome of any of the foregoing, is inherently uncertain.
Item 3. Legal Proceedings. In the ordinary course of business, we are or have been from time to time involved in lawsuits, investigations, proceedings and threats of litigation related to, among other things, our intellectual property estate (including the Patent Portfolio), commercial arrangements and other matters. Such proceedings may include quasi-litigation, inter partes administrative proceedings in the U.S.
Item 3. Legal Proceedings. In the ordinary course of business, we are or have been from time to time involved in lawsuits, investigations, proceedings and threats of litigation related to, among other things, our intellectual property estate (including the worldwide patent portfolio we have exclusively licensed from Dr. Charpentier), commercial arrangements and other matters.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

13 edited+0 added−0 removed28 unchanged
Biggest changeHolders As of February 16, 2024, 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. Dividends We have not paid any cash dividends on our common shares since inception and do not anticipate paying cash dividends in the foreseeable future.
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.
The subsequent purchase or sale of our shares, whether by Resident Private Shareholders, Domestic Commercial Shareholders or Non-Resident Shareholders (secondary market transactions), may be subject to the Swiss federal securities transfer stamp tax ( Umsatzabgabe ) at a current rate of up to 0.15%, calculated on the purchase price or the sale proceeds, respectively, if (i) such transfer 95 occurs through or with a Swiss or Liechtenstein bank or by or with involvement of another Swiss securities dealer as defined in the Swiss federal stamp tax duty act and (ii) no exemption applies.
The subsequent purchase or sale of our shares, whether by Resident Private Shareholders, Domestic Commercial Shareholders or Non-Resident Shareholders (secondary market transactions), may be subject to the Swiss federal securities transfer stamp tax ( Umsatzabgabe ) at a current rate of up to 0.15%, calculated on the purchase price or the sale proceeds, respectively, if (i) such transfer occurs through or with a Swiss or Liechtenstein bank or by or with involvement of another Swiss securities dealer as defined in the Swiss federal stamp tax duty act and (ii) no exemption applies.
Comparison of Total Return Among CRISPR Therapeutics AG, the NASDAQ Composite Index and the NASDAQ Biotechnology Index 94 Swiss Tax Considerations Swiss Withholding Tax Under present Swiss tax law, dividends due and similar cash or in-kind distributions made by us to a shareholder (including liquidation proceeds and stock dividends) are subject to Swiss federal withholding tax ( Verrechnungssteuer ) (“Withholding Tax”), currently at a rate of 35% (applicable to the gross amount of the taxable distribution).
Comparison of Total Return Among CRISPR Therapeutics AG, the Nasdaq Composite Index and the Nasdaq Biotechnology Index Swiss Tax Considerations Swiss Withholding Tax Under present Swiss tax law, dividends due and similar cash or in-kind distributions made by us to a shareholder (including liquidation proceeds and stock dividends) are subject to Swiss federal withholding tax ( Verrechnungssteuer ) (“Withholding Tax”), currently at a rate of 35% (applicable to the gross amount of the taxable distribution).
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 repurchased shares exceeds 10% of our share capital or (iii) if the repurchased shares are not resold within six years after the repurchase.
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.
Information will not be transferred automatically in the absence of consent, and instead will be exchanged 96 only within the scope of administrative assistance on the basis of the double taxation agreement between the United States and Switzerland.
Information will not be transferred automatically in the absence of consent, and instead will be exchanged only within the scope of administrative assistance on the basis of the double taxation agreement between the United States and Switzerland.
This graph assumes the investment of $100 on December 31, 2018 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, 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.
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. 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.
The graph set forth below compares the cumulative total stockholder return on our shares between December 31, 2018 and December 31, 2023, 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, 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.
Swiss Federal, Cantonal and Communal Individual Income Tax and Corporate Income Tax Non-Resident Shareholder s Non-Resident Shareholders are not subject to any Swiss federal, cantonal or communal income tax on dividend payments and similar distributions because of the mere holding of our shares. The same applies for capital gains on the sale of shares. For Withholding Tax consequences, see above.
Swiss Federal, Cantonal and Communal Individual Income Tax and Corporate Income Tax Non-Resident Shareholder s Non-Resident Shareholders are not subject to any Swiss federal, cantonal or communal income tax on dividend payments and similar distributions because of the mere holding of our shares. The same applies for capital gains on the sale of shares.
THE DISCUSSION ABOVE IS A SUMMARY OF MATERIAL SWISS TAX CONSIDERATIONS. IT DOES NOT COVER ALL TAX MATTERS THAT MAY BE OF IMPORTANCE TO A PARTICULAR SHAREHOLDER. EACH SHAREHOLDER IS URGED TO CONSULT ITS OWN TAX ADVISOR ABOUT THE TAX CONSEQUENCES TO IT IN LIGHT OF THE SHAREHOLDER’S OWN CIRCUMSTANCES.
THE DISCUSSION ABOVE IS A SUMMARY OF MATERIAL SWISS TAX CONSIDERATIONS. IT DOES NOT COVER ALL TAX MATTERS THAT MAY BE OF IMPORTANCE TO A PARTICULAR SHAREHOLDER.
Market Information Our common shares are traded on The Nasdaq Global Market under the symbol “CRSP.” Stock Performance Graph The following performance graph and related information shall not be deemed to be “soliciting material” or to be “filed” with the Securities and Exchange Commission, or SEC, for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, nor shall such information be incorporated by reference into any future filing under the Exchange Act or Securities Act of 1933, as amended, or the Securities Act, except to the extent that we specifically incorporate it by reference into such filing.
Securities and Exchange Commission, or SEC, for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or the Exchange Act, nor shall such information be incorporated by reference into any future filing under the Exchange Act or Securities Act of 1933, as amended, or the Securities Act, except to the extent that we specifically incorporate it by reference into such filing.
Securities authorized for issuance under equity compensation plans Information about our equity compensation plans is incorporated herein by reference to Item 12 of Part III of this Annual Report on Form 10-K. Item 6. Reserved Not applicable.
Dividends We have not paid any cash dividends on our common shares since inception and do not anticipate paying cash dividends in the foreseeable future. Securities authorized for issuance under equity compensation plans Information about our equity compensation plans is incorporated herein by reference to Item 12 of Part III of this Annual Report on Form 10-K. Item 6.
Item 5. Market for Registrant’s Common Equity, Related Stock holder Matters and Issuer Purchases of Equity Securities.
Item 5. Market for Registrant’s Common Equity, Related Stock holder Matters and Issuer Purchases of Equity Securities. Market Information Our common shares are traded on The Nasdaq Global Market under the symbol “CRSP.” Stock Performance Graph The following performance graph and related information shall not be deemed to be “soliciting material” or to be “filed” with the U.S.

Item 7. Management's Discussion & Analysis

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

80 edited+22 added−38 removed51 unchanged
Biggest changeThe following table summarizes our research and development expenses for the years ended December 31, 2023 and 2022, together with the changes in those items in dollars (in thousands): Years Ended December 31, Period to Period 2023 2022 Change External research and development expenses $ 130,124 $ 197,742 $ (67,618 ) Employee related expenses 83,316 81,683 1,633 Facility expenses 105,875 114,591 (8,716 ) Stock-based compensation expenses 46,356 53,956 (7,600 ) Other expenses 2,703 2,864 (161 ) Sublicense and license fees 18,958 10,809 8,149 Total research and development expenses $ 387,332 $ 461,645 $ (74,313 ) The decrease of approximately $74.3 million was primarily attributable to the following: • $67.6 million of decreased external research and development costs, primarily associated with a decrease in variable external research and manufacturing costs; 105 • $8.7 million of decreased facility expenses due to incurring rent expense on both our current and previous U.S. headquarters for research and development for a portion of 2022, whereas in 2023, we did not incur any rent expense on our previous U.S. headquarters for research and development due to the termination of the lease; • $7.6 million of decreased stock-based compensation expenses primarily due to an overall decrease in the fair value of equity awards granted in 2023 and 2022; offset by • $8.1 million of increased sublicense and license fees, primarily attributable to research and development licenses and milestones due to strategic partners in connection with the advancement of our clinical programs.
Biggest changeThe 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.
Hemoglobinopathies CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break.
Hemoglobinopathies CASGEVY CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break.
Other income (net) Other income 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.
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.
Investing Activities 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.
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.
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; • 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; 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.
Under the Amended A&R Vertex JDCA, 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.
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.
To the extent the transaction price includes variable consideration, such as research, development, regulatory and commercial milestones, we determine if it is probable that we will receive such amounts and there is no risk of a 102 significant revenue reversal.
To the extent the transaction price includes variable consideration, such as research, development, regulatory and commercial milestones, we determine if it is probable that we will receive such amounts and there is no risk of a significant revenue reversal.
We expect to continue to incur general and administrative expenses consistent with general and administrative functions at research and development companies of our size and stage of development, which may increase in the future to support continued 101 research and development activities, and potential commercialization of our product candidates.
We expect to continue to incur general and administrative expenses consistent with general and administrative functions at research and development companies of our size and stage of development, which may increase in the future to support continued research and development activities, and potential commercialization of our product candidates.
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 agreements.
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.
If we raise additional funds through collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us.
If we raise additional funds through license or collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us.
In Vivo 98 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.
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.
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 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 101 significant risks and rewards that are dependent on the commercial success of the activities, are recorded as collaborative arrangements.
To date, we have primarily financed our operations through private placements of our preferred shares, common share issuances, convertible loans and payments related to certain of our collaboration agreements with strategic partners.
To date, we have primarily financed our operations through private placements of our preferred shares, common share issuances, convertible loans and payments related to certain of our license and collaboration agreements with strategic partners.
General and administrative expenses General and administrative expenses consist primarily of employee related expenses, including salaries, benefits and equity-based compensation, for personnel in executive, finance, accounting, business development and human resources functions.
General and administrative expenses General and administrative expenses consist primarily of employee related expenses, including salaries, benefits and equity-based compensation, for personnel in executive, finance, accounting, business development, human resources and other general and administrative functions.
Sources of Liquidity Cash Flows Discussions of 2021 items and year-to-year comparisons between 2022 and 2021 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, 2022 filed with the SEC on February 21, 2023.
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.
In 2022, the sale of common shares pursuant to the 2019 Sales Agreement and the current 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 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.
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, 2023 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 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.
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; 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; establish 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; 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.
In the normal course of business, we enter into agreements with contract research organizations for clinical trials and clinical supply manufacturing and with vendors for preclinical research studies and other services and products for operating purposes. These contracts are generally cancelable at any time by us upon less than 180 days’ prior written notice.
In the normal course of business, we enter into agreements with CROs for clinical trials and clinical supply manufacturing and with vendors for preclinical research studies and other services and products for operating purposes. These contracts are generally cancelable at any time by us upon less than 180 days’ prior written notice.
CASGEVY is the first therapy to emerge from our strategic partnership with Vertex Pharmaceuticals Incorporated, or 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. In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world.
Overview We are a leading gene editing company focused on the development of CRISPR/Cas9-based therapeutics. CRISPR/Cas9 is a revolutionary technology for gene editing, the process of precisely altering specific sequences of genomic DNA. We aim to apply this technology to disrupt, delete, correct and insert genes to treat genetic diseases and to engineer advanced cellular therapies.
We 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.
We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect. Given our need for additional financing to support the long-term clinical development of our programs, we intend to consider additional financing opportunities when market terms are favorable to us.
We have based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we expect. Given our need for additional financing to support the long-term clinical development and future commercialization of our programs, as applicable, we intend to consider additional financing opportunities when market terms are favorable to us.
Outlook Based on our research and development plans and our timing expectations related to the progress of our programs, we expect our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditures for at least the next 24 months without giving effect to any additional proceeds we may receive under our collaboration with Vertex and any other capital raising transactions we may complete.
Outlook Based on our research and development plans and our timing expectations related to the progress of our programs, we expect our existing cash, cash equivalents and marketable securities will enable us to fund our operating expenses and capital expenditures for at least the next 24 months without giving effect to any additional proceeds we may receive under our license agreements and collaborations, including with Vertex, and any other capital raising transactions we may complete.
Immuno-Oncology and Autoimmune 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 have not included these commitments on our balance sheet because the achievement and timing of these milestones is not fixed and determinable. 108
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 exercised our option to defer our portion of specified costs incurred in 2022 and 2023 for the CASGEVY program in excess of the amounts described above. 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.
In 2024, 2023 and 2022, we exercised our option to defer our portion of specified costs incurred for the CASGEVY program in excess of the deferral limit. 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.
We expect to continue to incur research and development costs and general and administrative expenses, as well as expenses related to potential commercialization of our product candidates, consistent with costs associated with research and development at companies of our size and stage of development, and, as a result, we will need additional capital to fund our operations, which we may raise through public or private equity or debt financings, strategic collaborations, or other sources.
We expect to continue to incur research and development costs and general and administrative expenses, consistent with costs associated with research and development at companies of our size and stage of development, and, as a result, we will need additional capital to fund our operations, which we may raise through public or private equity or debt financings, strategic collaborations, or other sources.
For the years ended December 31, 2023, 2022 and 2021, we generated $1.2 million, $0.8 million and $1.9 million, respectively, of grant revenue related to certain contracts with not-for-profit entities.
For the years ended December 31, 2024, 2023 and 2022, we generated $2.3 million, $1.2 million and $0.8 million, respectively, of grant revenue related to certain contracts with not-for-profit entities.
Collaboration Arrangements We record the elements of our collaboration agreements that represent joint operating activities in accordance with ASC 808, Collaborative Arrangements , or ASC 808.
Collaboration Arrangements We record the elements of our collaboration agreements that represent joint operating activities in accordance with Accounting Standards Codification Topic 808, Collaborative Arrangements , or ASC 808.
We believe our gene editing capabilities have the potential to enable a beta-cell replacement product candidate that may deliver durable benefit to patients without the need for long-term immunosuppression. We have three parallel efforts to achieve this goal.
We believe our gene editing capabilities have the potential to enable a beta-cell replacement product candidate that may deliver durable benefit to patients without the need for long-term immunosuppression.
Revenue recognition We have not generated any revenue to date from product sales. During the years ended December 31, 2023, 2022 and 2021, we recognized $370.0 million, $0.4 million and $913.1 million, respectively, of collaboration revenue, which is primarily related to our collaboration agreements with Vertex.
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.
Financing Activities 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 $29.9 million from stock option exercises and employee stock purchase plan, or ESPP, contributions.
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.
While we were in a net income position in certain previous years due to upfront payments associated with our collaborations with Vertex, we have a history of recurring losses and expect to continue to incur losses for the foreseeable future. Our net losses may fluctuate significantly from quarter to quarter and year to year.
We have a history of recurring losses and expect to continue to incur losses for the foreseeable future; however, we have been in a net income position in certain previous years due to certain payments associated with our collaboration and license agreements with Vertex. Our net losses may fluctuate significantly from quarter to quarter and year to year.
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, 2023, we had $1,695.7 million in cash, cash equivalents and marketable securities, of which approximately $2.7 million was held outside of the United States, and an accumulated deficit of $999.7 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, 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.
We exercised our option to defer our portion of specified costs incurred in 2022 and 2023 for the CASGEVY program in excess of the deferral limit under the A&R Vertex JDCA, as amended. We deferred $80.9 million and $36.1 million of our share of costs incurred under the A&R Vertex JDCA, as amended, for 2023 and 2022, respectively.
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.
We have established a leading platform for in vivo gene editing and are rapidly advancing a broad portfolio of in vivo programs. 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.
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 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.
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.
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. 100 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 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.
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.
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.
Collaboration revenue was not significant for the year ended December 31, 2022. 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.
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.
CTX112 is being investigated in an ongoing clinical trial designed to assess the safety and efficacy of the candidate in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy.
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.
Although we and our partner, Vertex, received marketing approval of CASGEVY in 2023 in certain jurisdictions, and have received a subsequent approval in 2024, most of our programs are still in early stages of development and the outcome of these efforts is uncertain, 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 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.
In addition, the 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.
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.
In 2021, we issued and sold 1.4 million common shares at an average price of $168.23 per share for aggregate proceeds of $224.5 million, which were net of equity issuance costs of $3.1 million. An additional $2.3 million of stamp taxes related to this amount was paid in 2021.
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.
The following table provides information regarding our cash flows for each of the periods below: Years Ended December 31, 2023 2022 (in thousands) Net cash used in operating activities $ (260,375 ) $ (495,741 ) Net cash provided by (used in) investing activities 374,647 (258,655 ) Net cash provided by financing activities 62,664 38,592 Effect of exchange rate changes on cash 73 (80 ) Increase (decrease) in cash and restricted cash $ 177,009 $ (715,884 ) Operating Activities Net cash used in operating activities was $260.4 million for the year ended December 31, 2023, compared to net cash used in operating activities of $495.7 million for the year ended December 31, 2022.
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.
Future contractual payments on operating lease and sublease obligations due within one year of December 31, 2023 are $28.7 million, and future contractual payments on operating lease and sublease obligations due greater than one year from December 31, 2023 are $293.9 million.
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.
We believe that the combination of our technology, research and development capabilities, and proven ability to execute 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 rare and common diseases for whom current biopharmaceutical approaches have had limited success.
In addition, we continue to innovate on our platform to develop next-generation technologies that can enable new therapies. Through these efforts, we aim to unlock the full potential of CRISPR/Cas9 to create medicines that can transform the lives of patients. Our mission is to create transformative gene-based medicines for serious human diseases.
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 expect our research and development costs to increase for the foreseeable future as our current development programs progress, new programs are added and as we continue to prepare regulatory filings.
We expect to continue to incur research and development costs consistent with research and development at companies of our size and stage of development, which may increase in the foreseeable future as our current development programs progress, new programs are added and we continue to prepare regulatory filings.
Finally, we are pursuing additional delivery technologies, including further advancements to nanoparticle technology and AAV vectors, for delivery to tissues beyond the liver, including hematopoietic stem cells. Type 1 Diabetes We are advancing a series of programs focused on the development of gene-edited stem cell-derived therapies for the treatment of T1D.
Finally, we are pursuing additional delivery technologies, including LNPs, for delivery to tissues beyond the liver, including hematopoietic stem cells. Type 1 Diabetes We are developing gene-edited stem cell-derived therapies for the treatment of T1D.
We are advancing several cell therapy programs for oncology and/or autoimmune indications, including two next-generation allogeneic CAR T programs, CTX112 targeting CD19 and CTX131 targeting CD70. These product candidates incorporate two novel gene edits—knock-out of Regnase-1 and knock-out of transforming growth factor-beta receptor type 2, or TGFBR2—designed to enhance CAR T potency and reduce CAR T exhaustion.
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.
CTX131 is being investigated in an ongoing clinical trial designed to assess the safety and efficacy of the candidate in adult patients with relapsed or refractory solid tumors. In addition, we plan to expand trials of CTX131 into hematologic malignancies, including T- and B-cell malignancies.
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.
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.
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.
The increase of $20.0 million was attributable to our share of certain costs arising from a license agreement between Vertex and a third party, which we agreed to pay to Vertex upon the occurrence of an event specified in Amendment No. 1 to the A&R Vertex JDCA and further described in Note 8 of the notes to our consolidated financial statements included in this Annual Report on Form 10-K.
The decrease of $20.0 million was attributable to our share of certain costs in 2023 arising from a license agreement between Vertex and a third party, which we agreed to pay to Vertex upon the occurrence of an event specified in Amendment No. 1 to the A&R Vertex JDCA. No similar costs were incurred in 2024.
Net cash used in investing activities for the year ended December 31, 2022 was $258.7 million and consisted primarily of purchases of marketable securities in excess of maturities of marketable securities of $221.5 million, as well as purchases of property, plant and equipment of $37.2 million.
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.
Examples of estimated accrued research and development expenses include fees paid to: • CROs in connection with clinical studies; • investigative sites in connection with clinical studies; • vendors in connection with preclinical development activities; and • vendors related to development, manufacturing and distribution of clinical trial materials. 103 We base our expenses related to clinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple CROs that conduct and manage clinical studies on our behalf.
Examples of estimated accrued research and development expenses include fees paid to: • CROs in connection with clinical studies; • investigative sites in connection with clinical studies; • vendors in connection with preclinical development activities; and • vendors related to development, manufacturing and distribution of clinical trial materials.
An additional $0.3 million of stamp taxes related to this amount was paid in 2023. 106 As of December 31, 2023, we have $385.6 million remaining under our current prospectus supplement and have issued and sold an aggregate of 1.5 million common shares at an average price of $139.91 per share for aggregate proceeds of $211.5 million, which were net of equity issuance costs of $2.9 million.
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.
We have entered into a number of additional collaborations and license agreements to support and complement our hematopoietic stem cell, immuno-oncology and autoimmune, 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 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 immuno-oncology 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.
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 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.
Other income, net Other income, net, was $71.8 million for the year ended December 31, 2023, compared to $22.7 million for the year ended December 31, 2022. The increase in other income, net, was due to higher interest rates.
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.
As a result, we may face difficulties raising capital through sales of our common shares or such sales may be on unfavorable terms.
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.
For example, our first two in vivo programs, CTX310 and CTX320, aim to address cardiovascular disease by disrupting the validated targets ANGPTL3 and Lp(a), respectively. We have initiated Phase 1 clinical trials for both CTX310 and CTX320.
Cardiovascular disease Our first two in vivo programs utilizing our proprietary LNP platform, CTX310 and CTX320, aim to address cardiovascular disease by disrupting the validated targets angiopoietin-like protein 3, or ANGPTL3, and lipoprotein (a), or Lp(a), respectively.
Grant Revenue Grant revenue was $1.2 million and $0.8 million, respectively, for the years ended December 31, 2023 and 2022. Research and Development Expenses Research and development expenses were $387.3 million for the year ended December 31, 2023, compared to $461.6 million for the year ended December 31, 2022.
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.
Collaboration expense, net Collaboration expense, net, was $130.3 million for the year ended December 31, 2023, compared to $110.3 million for the year ended December 31, 2022.
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.
To date, CASGEVY has been approved in the United States, Europe, Great Britain, Saudi Arabia, and Bahrain for the treatment of eligible patients 12 years and older with SCD or TDT. 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.
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.
In April 2021, we and Vertex amended and restated our existing joint development and commercialization agreement, pursuant to which, among 99 other things, we will continue to develop and commercialize CASGEVY for TDT and SCD in partnership with Vertex.
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 .
ViaCyte . We entered into a research and collaboration agreement in September 2018 with ViaCyte to pursue the discovery, development and commercialization of gene-edited allogeneic stem cell therapies for the treatment of diabetes, and in July 2021, we entered into a joint development and commercialization agreement with ViaCyte, or the ViaCyte JDCA.
Beginning in 2018, we partnered with ViaCyte, Inc., or ViaCyte (now a wholly-owned subsidiary of Vertex), to pursue the discovery, development and commercialization of gene-edited allogeneic stem cell therapies for the treatment of diabetes. In 2023, ViaCyte elected to opt-out of the collaboration with us for the co-development and co-commercialization of gene-edited stem cell therapies for the treatment of diabetes.
Payments under some of these contracts depend on factors such as the successful enrollment of subjects and the completion of clinical study milestones. 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.
There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the clinical expense. Payments under some of these contracts depend on factors such as the successful enrollment of subjects and the completion of clinical study milestones.
Partnerships Given the numerous potential therapeutic applications for CRISPR/Cas9, we have partnered strategically to broaden the indications we can pursue and to accelerate programs by accessing specific technologies and/or disease-area expertise. For additional information regarding certain of these partnerships, please see “ Business—Strategic Partnerships and Collaborations .” Vertex.
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.
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. Results of Operations The following is a discussion of the components of results of operations. This section generally discusses 2023 and 2022 items and year-to-year comparisons between 2023 and 2022.
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.
We also entered into a strategic collaboration and license agreement with Vertex in June 2019 for the development and commercialization of products for the treatment of Duchenne muscular dystrophy, or DMD, and myotonic dystrophy type 1, or DM1 and, in March 2023, we entered into a non-exclusive license agreement with Vertex for Vertex to utilize our gene editing technology in diabetes.
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.
Net cash provided by financing activities for the year ended December 31, 2022 was $38.6 million and consisted primarily of net proceeds of $37.6 million from stock option exercises and ESPP contributions.
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.
Building upon CTX310 and CTX320, we have a number of earlier stage investigational in vivo programs leveraging gene disruption in the liver for both rare and common diseases. In addition, we have programs focused on gene correction in the liver, including programs leveraging technologies developed by our CRISPR-X research team.
Additional candidates Building upon CTX310 and CTX320, we are progressing CTX340, targeting angiotensinogen for refractory hypertension, as well as CTX450, targeting 5’-aminolevulinate synthase 1 for acute hepatic porphyria, through preclinical studies. In addition, we have programs focused on gene correction in the liver, including programs leveraging technologies developed by our CRISPR-X research team.
In December 2023, ViaCyte elected to opt-out of the collaboration with us for the co-development and co-commercialization of gene-edited stem cell therapies for the treatment of diabetes. Per the opt-out terms, once the opt-out is complete, the on-going collaboration assets will be wholly owned by us, subject to a royalty on future sales owed to ViaCyte.
Per the opt-out terms, the on-going collaboration assets will be wholly owned by us, subject to a royalty on future sales owed to ViaCyte. Our product candidate, CTX211, being developed for the potential treatment of T1D, resulted from this collaboration, and which we are continuing to advance in a Phase 1 clinical trial.
Third, 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, for which we received $170 million in upfront and milestone payments in 2023 and remain eligible to receive additional research and development milestones and royalties on future products.
To date, we have recognized revenue of $205 million in upfront and milestone payments and remain eligible to receive additional research and development milestones and royalties on future products under the license. Other Partnerships .
Discussions of 2021 items and year-to-year comparisons between 2022 and 2021 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, 2022 filed with the SEC on February 21, 2023. 104 Comparison of Years Ended December 31, 2023 and 2022 The following table summarizes our results of operations for the years ended December 31, 2023 and 2022, together with the dollar change in those items: Years Ended December 31, Period to 2023 2022 Period Change (in thousands) Revenue: Collaboration revenue $ 370,000 $ 436 $ 369,564 Grant revenue 1,206 762 444 Total revenue 371,206 1,198 370,008 Operating expenses: Research and development 387,332 461,645 (74,313 ) General and administrative 76,162 102,464 (26,302 ) Collaboration expense, net 130,250 110,250 20,000 Total operating expenses 593,744 674,359 (80,615 ) Loss from operations (222,538 ) (673,161 ) 450,623 Other income, net 71,816 22,661 49,155 Net loss before income taxes (150,722 ) (650,500 ) 499,778 (Provision) benefit for income taxes (2,888 ) 325 (3,213 ) Net loss $ (153,610 ) $ (650,175 ) $ 496,565 Collaboration Revenue Collaboration revenue was $370.0 million for the year ended December 31, 2023, compared to $0.4 million for the year ended December 31, 2022.
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.
These deferred costs will be recognized by us when recoverability of such deferred amounts by Vertex is probable and the amount can be reasonably estimated. As of December 31, 2023, no such deferred amounts have been recognized. Refer to Note 8 for further discussion of our arrangements with Vertex.
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. These deferred costs on the CASGEVY program will be recognized by us when recoverability of such deferred amounts by Vertex is probable and the amount can be reasonably estimated.
The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the clinical expense.
We base our expenses related to clinical studies on our estimates of the services received and efforts expended pursuant to contracts with multiple CROs that conduct and manage clinical studies on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows.
Collaboration revenue for the year ended December 31, 2023 was primarily associated with the $370.0 million of payments from Vertex in connection with (i) the approval of CASGEVY, which triggered Vertex’s obligation to make a $200.0 million milestone payment to us, which is included in accounts receivable in the accompanying consolidated balance sheets as of December 31, 2023, and (ii) the Non-Ex License Agreement, pursuant to which we agreed to license to Vertex, on a non-exclusive basis, 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, which resulted in upfront and milestone payments of $170.0 million in 2023.
Collaboration revenue for the year ended December 31, 2023 was related to (i) the achievement of a $200.0 million milestone in connection with the approval of CASGEVY under our collaboration with Vertex and (ii) an upfront payment of $100.0 million and a milestone achieved of $70.0 million under the Non-Ex License Agreement with Vertex.
The decrease in cash used in operating activities was primarily driven by $170.0 million of upfront and milestone payments from Vertex, as well as reductions in research and development and general and administrative expenses as described above.
The decrease in cash used in operating activities was primarily driven by cash received in 2024 from Vertex in connection with the $200.0 million milestone achieved upon regulatory approval of CASGEVY in 2023, offset by increased net losses.
The opt-out became effective in early February 2024. The ViaCyte collaboration assets include CTX211 (formerly VCTX211), 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. We are continuing to advance a Phase 1 clinical trial for CTX211 for the treatment of T1D.
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.

… 60 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, 2023, 2022 and 2021.
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.
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, 2023, we had cash, cash equivalents and marketable securities of $1,695.7 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, 2024, we had cash, cash equivalents and marketable securities of $1,903.8 million, primarily invested in U.S.

Other CRSP 10-K year-over-year comparisons