CRISPR Therapeutics AG

Previous wording

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 have advanced this technology from discovery to an approved medicine with unparalleled speed, culminating in the landmark first approval of a CRISPR-based therapy, CASGEVY (exagamglogene autotemcel [exa-cel]), in 2023 with our collaborators at Vertex Pharmaceuticals Incorporated, or Vertex. We 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.

Current wording

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

Previous wording

Our mission is to create transformative gene-based medicines for serious human diseases. We believe that our innovative research, translational expertise and clinical development experience position us as a leader in the development of CRISPR-based therapeutics.

Current wording

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 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.

Previous wording

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. This edit results in the production of high levels of fetal hemoglobin in red blood cells, which can compensate for the defective adult hemoglobin in patients with SCD and TDT. 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.

Current wording

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. This edit results in the production of high levels of fetal hemoglobin in red blood cells, which can compensate for the defective adult hemoglobin in patients with SCD and TDT. 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.

Previous wording

In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world. To date, CASGEVY has been approved in the United States, 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.

Current wording

In 2023, CASGEVY became the first-ever approved CRISPR-based gene-editing therapy in the world. To date, CASGEVY has been approved in the United States, European Union, Great Britain, Canada, Switzerland, Kingdom of Saudi Arabia, Kingdom of

Previous wording

We believe CRISPR/Cas9 has the potential to create the next generation of CAR T cell therapies that may have a superior product profile and allow broader patient access compared to current autologous therapies. We are advancing 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. Emerging pharmacology data, including pharmacokinetics, from ongoing clinical trials of CTX112 and CTX131, indicate that the novel potency gene edits lead to significantly higher CAR T cell expansion and functional persistence in patients compared to our first-generation candidates that did not incorporate these edits. 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.

Current wording

We believe CRISPR/Cas9 has the potential to create the next generation of CAR T cell therapies that may have a superior product profile and allow broader patient access compared to current autologous therapies. We are advancing 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. 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.

Previous wording

Ourin 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. We have established a leading platform forin vivo gene editing and are rapidly advancing a broad portfolio ofin vivo programs. Our firstin 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, our first twoin 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. 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. 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.

Current wording

Ourin 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. We have established a leading platform forin vivo gene editing and are rapidly advancing a broad portfolio ofin vivo programs, supported by an internal lipid nanoparticle, or LNP, team to enable liver-directed and extrahepatic programs with novel lipids, formulations, and targeting moieties. Our firstin 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.

Previous wording

We are advancing a series of programs focused on the development of gene-edited stem cell-derived therapies for the treatment of T1D. 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. First, our most advanced product candidate, CTX211, is 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. This program, formerly known as VCTX211, originated from our collaboration with ViaCyte, Inc., a subsidiary of Vertex, and was developed by applying our gene editing technology to ViaCyte’s proprietary stem cell capabilities. CTX211 is being investigated in an ongoing Phase 1/2 clinical trial designed to assess the safety, tolerability and efficacy of CTX211 in adult patients with T1D. Second, we have research efforts focused on a deviceless beta cell replacement approach consisting of unencapsulated beta cells derived from edited stem cells. 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.

Current wording

We are developing gene-edited stem cell-derived therapies for the treatment of T1D. 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: (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.

Previous wording

While we have made significant progress with our current portfolio of programs, we recognize that we need to continue to innovate to unlock the full power of gene editing and bring potentially transformative therapies to even more patients. We have a dedicated early-stage research team called CRISPR-X that focuses on innovating next-generation editing modalities. CRISPR-X is developing technologies to enable whole gene correction and insertion without requiring homology-directed repair or viral delivery of DNA, such as all-RNA gene correction, non-viral delivery of DNA and novel gene insertion techniques.

Current wording

While we have made significant progress with our current portfolio of programs, we recognize that we need to continue to innovate to unlock the full power of gene editing and bring potentially transformative therapies to even more patients. We have a dedicated early-stage research team called CRISPR-X that focuses on innovating next-generation editing modalities. 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.

Previous wording

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.”

Current wording

Given the numerous potential therapeutic applications for CRISPR/Cas9, we have partnered strategically to broaden the indications we can pursue and accelerate development of programs by accessing specific technologies and/or disease-area expertise. We maintain broad partnerships to develop gene editing-based therapeutics in specific disease areas. For additional information regarding certain of these partnerships, please see “Business—Strategic Partnerships and Collaborations.”

Previous wording

Vertex. We established our initial collaboration agreement in 2015 with Vertex, which focused on TDT, SCD, cystic fibrosis and select additional indications. In December 2017, we entered into a joint development and commercialization agreement with Vertex pursuant to which, among other things, we are co-developing and co-commercializing CASGEVY for TDT and SCD. In April 2021, we and Vertex amended and restated our existing joint development and commercialization agreement, pursuant to which, among other things, we will continue to develop and commercialize CASGEVY for TDT and SCD in partnership with Vertex. 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.

Current wording

Hemoglobinopathies. In 2015, we partnered with Vertex and entered into a strategic collaboration, option and license agreement, which focused on the discovery and development of gene-based treatments for hemoglobinopathies and cystic fibrosis using CRISPR/Cas9 gene-editing technology. 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.

Previous wording

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. In connection with entering into the ViaCyte JDCA, our existing research collaboration agreement with ViaCyte expired in accordance with its terms. In the third quarter of 2022, Vertex announced it had acquired ViaCyte and the rights to the ViaCyte Collaboration Field, and in March 2023, we entered into an amendment to the ViaCyte JDCA pursuant to which, among other things, we adjusted certain rights and obligations of the parties thereunder. 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. 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.

Current wording

Diabetes. 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. 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. 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. 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.

Previous wording

Other Partnerships. 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 developin 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. onex vivo delivery for our hemoglobinopathy and immuno-oncology programs; CureVac AG on optimized mRNA constructs and manufacturing for certainin vivo programs; and KSQ Therapeutics, Inc. on intellectual property for our allogeneic immuno-oncology programs.

Current wording

Other Partnerships. We have entered into a number of additional collaborations and license agreements in other therapeutic areas, including an additional agreement with Vertex for the treatment of Duchenne muscular dystrophy 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 developin 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. onex vivo delivery for our hemoglobinopathy and CAR T programs; CureVac AG on optimized mRNA constructs and manufacturing for certainin vivo programs; and KSQ Therapeutics, Inc. on intellectual property for our allogeneic immuno-oncology programs.

Previous wording

Since our inception in October 2013, we have devoted substantially all of our resources to our research and development efforts, 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. 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.

Current wording

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. 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.

Previous wording

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 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.

Current wording

We have a history of recurring losses and expect to continue to incur losses for the foreseeable future; however, we have been in a net income position in certain previous years due to certain payments associated with our collaboration and license agreements with Vertex. Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase as we continue our current research programs and development activities; seek to identify additional research programs and additional product candidates; conduct initial drug application supporting preclinical studies and initiate clinical trials for our product candidates; 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.

Previous wording

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.

Current wording

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.

Previous wording

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.

Current wording

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.

Previous wording

Research and development activities are central to our business model. 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. These increases will likely include the costs related to the implementation and expansion of clinical trial sites and related patient enrollment, monitoring, program management and manufacturing expenses for current and future clinical trials.

Current wording

Research and development activities are central to our business model. 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. These increases will likely include the costs related to the implementation and expansion of clinical trial sites and related patient enrollment, monitoring, program management and manufacturing expenses for current and future clinical trials.

Previous wording

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. Other significant costs include facility costs not otherwise included in research and development expenses, legal fees relating to patent and corporate matters and fees for accounting and consulting services.

Current wording

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. Other significant costs include facility costs not otherwise included in research and development expenses, legal fees relating to patent and corporate matters and fees for accounting and consulting services.

Previous wording

Collaboration expense, net, consists of operating expenses related to the CASGEVY program under our collaboration with Vertex. 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. The $110.3 million for 2023 does not include amounts 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. 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.

Current wording

Collaboration expense, net, consists of operating expenses related to the CASGEVY program under our collaboration with Vertex. 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. The $110.3 million for 2023 does not include amounts 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. 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.

Previous wording

Other income consists primarily of interest income earned on investments.

Current wording

Other income, net consists primarily of interest income earned on investments.

Previous wording

We record the elements of our collaboration agreements that represent joint operating activities in accordance with ASC 808, Collaborative Arrangements, or ASC 808. 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.

Current wording

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. 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.

Previous wording

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. 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 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.

Current wording

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. Collaboration revenue for the year ended December 31, 2024 was related to Vertex's achievement of a $10.0 million research milestone and $25.0 million research milestone under the Non-Ex License Agreement with Vertex in the fourth quarter of 2024. Collaboration revenue for the year ended December 31, 2023 was related to (i) the achievement of a $200.0 million milestone in connection with the approval of CASGEVY under our collaboration with Vertex and (ii) an upfront payment of $100.0 million and a milestone achieved of $70.0 million under the Non-Ex License Agreement with Vertex. Refer to Note 8 of the notes to our consolidated financial statements included in this Annual Report on Form 10-K for a description of revenue recognized related to Vertex.

Previous wording

Grant revenue was $1.2 million and $0.8 million, respectively, for the years ended December 31, 2023 and 2022.

Current wording

Grant revenue was $2.3 million and $1.2 million, respectively, for the years ended December 31, 2024 and 2023.

Previous wording

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. The 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):

Current wording

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. The following table summarizes our research and development expenses for the years ended December 31, 2024 and 2023, together with the changes in those items in dollars (in thousands):

Previous wording

The decrease of approximately $74.3 million was primarily attributable to the following:

Current wording

The decrease of approximately $66.7 million was primarily attributable to the following:

Previous wording

$67.6 million of decreased external research and development costs, primarily associated with a decrease in variable external research and manufacturing costs;

Current wording

$39.5 million of decreased external research and development costs, primarily associated with a decrease in variable external research and manufacturing costs;

Previous wording

$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.

Current wording

$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;

Previous wording

General and administrative expenses were $76.2 million for the year ended December 31, 2023, compared to $102.5 million for the year ended December 31, 2022. The decrease of $26.3 million was primarily attributable to decreased stock-based compensation, decreased professional services including intellectual property costs, decreased facility costs as described above, as well as decreased headcount-related expenses.

Current wording

General and administrative expenses were $73.0 million for the year ended December 31, 2024, compared to $76.2 million for the year ended December 31, 2023. The decrease of $3.2 million was primarily attributable to decreased employee-related expenses and consulting and professional services-related expenses.

Previous wording

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 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.

Current wording

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. 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. 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.

Previous wording

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. 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.

Current wording

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. 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. As of December 31, 2024, no contingent payments have been accrued to date. Refer to Note 8 of the notes to our consolidated financial statements in this Annual Report on Form 10-K for further discussion on our arrangements with Vertex.

Previous wording

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.

Current wording

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.

Previous wording

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. We anticipate that we will continue to incur losses for at least the next several years. We expect to continue to incur research and development costs and general and administrative expenses, 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.

Current wording

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 anticipate that we will continue to incur losses for at least the next several years. We expect to continue to incur research and development costs and general and administrative expenses, consistent with costs associated with research and development at companies of our size and stage of development, and, as a result, we will need additional capital to fund our operations, which we may raise through public or private equity or debt financings, strategic collaborations, or other sources.

Previous wording

In August 2019, we entered into an Open Market Sale Agreement SM with Jefferies under which we were able to offer and sell, from time to time at our sole discretion through Jefferies, as our sales agent, our common shares, par value of CHF 0.03 per share, or the August 2019 Sales Agreement. 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.

Current wording

In August 2019, we entered into an Open Market Sale Agreement SM with Jefferies under which we were able to offer and sell, from time to time at our sole discretion through Jefferies, as our sales agent, our common shares, par value of CHF 0.03 per share, or the August 2019 Sales Agreement. 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.

Previous wording

In 2022, the sale of common shares pursuant to the 2019 Sales Agreement and the current prospectus supplement was not significant.

Current wording

In 2022, the sale of common shares pursuant to the 2019 Sales Agreement and the applicable prospectus supplement was not significant.

Previous wording

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.

Current wording

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. An additional $0.2 million of stamp taxes related to this amount was paid in 2024.

Previous wording

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.

Current wording

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.

Previous wording

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 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.

Current wording

Net cash used in operating activities was $142.8 million for the year ended December 31, 2024, compared to net cash used in operating activities of $260.4 million for the year ended December 31, 2023. The 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.

Previous wording

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 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.

Current wording

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. 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.

Previous wording

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, 2022 was $38.6 million and consisted primarily of net proceeds of $37.6 million from stock option exercises and ESPP contributions.

Current wording

Net cash provided by financing activities for the year ended December 31, 2024 was $332.0 million and primarily consisted of net proceeds of approximately $279.0 million from the issuance of common shares in connection with our registered direct offering, net proceeds of approximately $31.2 million from stock option exercises, and net proceeds of approximately $21.7 million from the issuance of common shares in connection with our 2021 ATM. Net cash provided by financing activities for the year ended December 31, 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.

Previous wording

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. 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. We intend to consider opportunities to raise additional funds through the sale of equity or debt securities when market conditions are favorable to us to do so. However, the trading prices for our common shares and other biopharmaceutical companies have been highly volatile. As a result, we may face difficulties raising capital through sales of our common shares or such sales may be on unfavorable terms. In addition, a recession, depression or other sustained adverse market event, including resulting from the continued spread of the coronavirus or the recent failure of certain banks and financial institutions in the United States and globally, could materially and adversely affect our business and the value of our common shares. To the extent that we raise additional capital through the future sale of equity or debt securities, the ownership interests of our shareholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing shareholders. If we raise additional funds through collaboration arrangements in the future, we may have to relinquish valuable rights to our technologies, future revenue streams or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Current wording

Although we and our partner, Vertex, have received marketing approvals for CASGEVY in certain jurisdictions, we cannot guarantee we and Vertex will receive additional marketing approvals for CASGEVY or we will receive marketing approvals for our other product candidates in the future. 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. 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. We intend to consider opportunities to raise additional funds through the sale of equity or debt securities when market conditions are favorable to us to do so. However, the trading prices for our common shares and other biopharmaceutical companies have been highly volatile. As a result, we may face difficulties raising capital through sales of our common shares or such sales may be on unfavorable terms. In addition, a recession, depression or other sustained adverse market event could materially and adversely affect our business and the value of our common shares. To the extent that we raise additional capital through the future sale of equity or debt securities, the ownership interests of our shareholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing shareholders. 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. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.