CRISPR Therapeutics Stock

CRISPR Therapeutics AG, a gene editing company, focuses on the development of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9)-based therapeutics.

The company intends to apply this technology to disrupt, delete, correct and insert genes to treat genetically defined diseases and to engineer advanced cellular therapies. The company’s scientific expertise, together with its gene editing approach, may enable 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.

The company has acquired rights to the intellectual property encompassing CRISPR/Cas9 and related technologies from Dr. Charpentier and continue to strengthen its intellectual property estate through its own research and additional in-licensing efforts, furthering its leadership in the development of CRISPR/Cas9-based therapeutics.

The company has established a portfolio of therapeutic programs in a broad range of disease areas across four core franchises: hemoglobinopathies, immuno-oncology, regenerative medicine and in vivo approaches. The company’s most advanced programs target the genetically defined diseases transfusion-dependent beta thalassemia, or TDT, and severe sickle cell disease, or SCD, two hemoglobinopathies with high unmet medical need. The company is also progressing several gene-edited allogeneic cell therapy programs, including allogeneic chimeric antigen receptor T cell, or CAR T, candidates for the treatment of hematological and solid tumor cancers, and investigational, allogeneic, gene-edited, immune-evasive, stem cell-derived therapies for the treatment of type 1 diabetes, or T1D. In addition, the company is advancing multiple programs leveraging in vivo editing approaches, initially for the treatment and prevention of cardiovascular disease.

The company’s product development and partnership strategies are designed to exploit the full potential of the CRISPR/Cas9 platform while maximizing the probability of successfully developing its product candidates. For its most advanced product candidates, the company has taken an ex vivo approach in which it edits cells outside of the human body using CRISPR/Cas9 before administering them to the patient. In contrast, for the company’s in vivo editing programs, it delivers the CRISPR/Cas9-based therapeutic directly to target cells within the human body.

Hemoglobinopathies

The company’s lead product candidate, exagamglogene autotemcel, or exa-cel is an investigational, autologous, ex vivo CRISPR gene-edited hematopoietic stem cell therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are engineered ex vivo to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth and is then replaced by the adult form of hemoglobin. The elevation of HbF by exa-cel has the potential to eliminate transfusion requirements for TDT patients and painful and debilitating vaso-occlusive crises for SCD patients. Exa-cel is being developed under a joint development and commercialization agreement between the company and Vertex Pharmaceuticals Incorporated, or Vertex.

The company and Vertex are investigating exa-cel in two ongoing Phase 1/2/3 open-label clinical trials that are designed to assess the safety and efficacy of a single dose of exa-cel in patients ages 12 to 35 with TDT (CLIMB-111) or SCD (CLIMB-121), respectively. Enrollment is complete for both CLIMB-111 and CLIMB-121. The company and Vertex have also initiated two additional Phase 3 open-label clinical trials of exa-cel in pediatric patients with TDT (CLIMB-141) and SCD (CLIMB-151). Patients who received exa-cel in CLIMB-111, CLIMB-121, CLIMB-141 or CLIMB-151 will be asked to participate in a long-term, open-label follow-up trial, CLIMB-131, to evaluate the safety and efficacy of exa-cel. CLIMB-131 is designed to follow participants for up to 15 years after exa-cel infusion. In the second and fourth quarters of 2022, at the European Hematology Association Congress and American Society of Hematology Annual Meeting, respectively, the company presented updated clinical data from CLIMB-111 and CLIMB-121 for 44 patients with TDT and 31 patients with SCD treated with exa-cel.

Exa-cel has been granted a number of regulatory designations from the U.S. Food and Drug Administration, or FDA, specifically Regenerative Medicine Advanced Therapy, or RMAT, Fast Track, Orphan Drug, and Rare Pediatric Disease designations for the treatment of both TDT and SCD. Exa-cel has also been granted Orphan Drug Designation from the European Commission, as well as the PRIority MEdicines, or PRIME, designation from the European Medicines Agency, or EMA, for the treatment of both TDT and SCD.

In December 2022, the company and Vertex completed regulatory submissions for exa-cel with the EMA and the Medicines and Healthcare products Regulatory Agency, or MHRA, in the EU and the U.K., respectively, and both the EMA and the MHRA have validated the Marketing Authorization Application, or MAA, respectively. In addition, the company and Vertex initiated the rolling submission of its Biologics Licensing Application, or BLA, in the United States in November 2022 and expects to complete the submission by the end of the first quarter of 2023.

Finally, building upon exa-cel, the company has next-generation efforts in targeted conditioning regimens and in vivo editing of hematopoietic stem cells, either of which could broaden the number of patients that could benefit from its therapies.

Immuno-Oncology

CRISPR/Cas9 has the potential to create the next generation of CAR T cell therapies that may have a superior product profile compared to current autologous therapies and allow accessibility to broader patient populations. Drawing from the ex vivo gene editing capabilities gained through the company’s lead programs, it is advancing several immuno-oncology cell therapy programs, including allogeneic CAR T programs targeting CD19 and CD70.

CD19 Franchise

CTX110, the company’s lead immuno-oncology product candidate, is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting Cluster of Differentiation 19, or CD19. The company is investigating CTX110 in its CARBON clinical trials, which are designed to assess the safety and efficacy of CTX110 in adult patients with relapsed or refractory CD19-positive B-cell malignancies who have received at least two prior lines of therapy. CTX110 has been granted RMAT designation by the FDA.

The Phase 1 CARBON clinical trial is being conducted in two parts – Part A and Part B. In Part A of the Phase 1 CARBON clinical trial, or Phase 1 Part A, patients were infused with a single dose of CTX110 across escalating dose levels following a standard lymphodepletion regimen, with an option to re-dose CTX110 based on clinical benefit. In Part B of the Phase 1 CARBON clinical trial, or Phase 1 Part B, patients received CTX110 at Dose Level (DL) 4 following standard lymphodepletion, as well as a consolidation dose of CTX110 at the same dose level between four and eight weeks after the initial dose for patients that demonstrated clinical benefit.

In the fourth quarter of 2022, the company presented updated clinical data from Phase 1 Part A for 32 patients treated with CTX110, which showed the potential for CTX110 to achieve long-term durable complete remissions, or CRs, with a positively differentiated safety profile in heavily pre-treated patients, and described emerging data from Phase 1 Part B, which showed an encouraging efficacy profile with the potential to improve efficacy with the use of a consolidation dose. Based on this emerging data from its Phase 1 CARBON clinical trial and discussions with regulatory agencies, the company has expanded CARBON to include a Phase 2, potentially registrational, single-arm, multi-center, open-label clinical trial that incorporates consolidation dosing. The company has begun dosing patients in this pivotal arm.

In parallel with CTX110, the company is advancing CTX112, a next-generation investigational, allogeneic CAR T product candidate targeting CD19. CTX112 includes two additional edits beyond CTX110, making use of the fact that its CRISPR/Cas9 platform enables it to innovate continuously by incorporating incremental edits into next-generation products. These edits target the genes encoding Regnase-1 and transforming growth factor-beta receptor type 2 (TGFBR2) with the aim of enhancing CAR T potency and reducing CAR T exhaustion. In the fourth quarter of 2022, the Investigational New Drug, or IND, application for CTX112 was cleared by the FDA.

CD70 Franchise

CTX130 is a healthy donor-derived gene-edited allogeneic CAR T investigational therapy targeting Cluster of Differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being investigated in two ongoing independent Phase 1, single-arm, multi-center, open-label clinical trials that are designed to assess the safety and efficacy of several dose levels of CTX130 in adult patients. The COBALT-LYM trial is evaluating the safety and efficacy of CTX130 for the treatment of relapsed or refractory T or B cell malignancies. The COBALT-RCC trial is evaluating the safety and efficacy of CTX130 for the treatment of relapsed or refractory clear cell renal cell carcinoma. CTX130 has received Orphan Drug Designation from the FDA for the treatment of T cell lymphoma and RMAT designation for the treatment of Mycosis Fungoides and Sezary Syndrome (MF/SS), subtypes of Cutaneous T cell Lymphoma (CTCL). In the second quarter of 2022, at the European Hematology Association Congress, the company released initial clinical data from the ongoing COBALT-LYM trial for 18 patients with T cell lymphoma treated with CTX130 who had reached at least 28 days of follow-up. Also, in the fourth quarter of 2022, at the Society of Immuno-therapy in Cancer Annual Meeting, the company released initial clinical data from the COBALT-RCC trial for 14 patients.

In parallel with CTX130, the company is advancing CTX131, a next-generation investigational, allogeneic CAR T product candidate targeting CD70 for the potential treatment of both solid tumors and certain hematologic malignancies. CTX131 includes two additional edits beyond CTX130. These edits, the same used in CTX112, target the genes encoding Regnase-1 and TGFBR2 with the aim of enhancing CAR T potency and reducing CAR T exhaustion; and in the first quarter of 2023, the IND for CTX131 was cleared by the FDA.

Additional Candidates

The company is advancing several additional CAR T product candidates. For two such candidates, the company has developed an innovative partnership model with leading cancer centers to validate the novel targets Cluster of Differentiation 83, or CD83, and glypican-3, or GPC3, in the clinic. In partnership with Moffitt Cancer Center, the company is advancing an autologous CAR T candidate targeting CD83, which has potential to treat acute myeloid leukemia and other oncology and autoimmune indications. With Roswell Park Comprehensive Cancer Center, the company is advancing a gene-edited, autologous CAR T candidate targeting GPC3, expressed in hepatocellular carcinoma. In both cases, its academic partners will conduct manufacturing and first-in-human clinical trials. This structure will enable the company to assess the safety and activity of these targets rapidly. Based on the clinical results, it can choose to continue advancing these autologous programs internally or develop allogeneic versions to expand the opportunity further. In addition, beyond CAR T, the company formed a collaboration with Nkarta, Inc., or Nkarta, that brings together its gene editing technology and cell therapy expertise with Nkarta’s leading natural killer (NK) cell discovery, development and manufacturing capabilities. As part of that collaboration the company and Nkarta are co-developing and co-commercializing a donor-derived, gene-edited CAR-NK cell product candidate targeting CD70.

Regenerative Medicine

Building upon its ex vivo gene editing expertise, the company has expanded its efforts in this field with a focus on allogeneic stem cell-derived therapies gene edited using CRISPR/Cas9 to enable immune evasion, improve cell function, and direct cell fate. The company’s first major effort in this area is in diabetes, and it and ViaCyte, Inc., which was acquired by Vertex in the third quarter of 2022, or ViaCyte, are advancing a series of programs as part of a strategic collaboration for the discovery, development and commercialization of gene-edited stem cell therapies for the treatment of diabetes.

The company has a multi-staged product strategy that leverages its CRISPR/Cas9 platform to advance multiple product candidates incorporating incremental edits designed to increase benefit. The company’s initial product candidate, VCTX210, is an investigational, allogeneic, gene-edited, immune-evasive, stem cell-derived product candidate for the treatment of T1D developed by applying its gene editing technology to ViaCyte’s proprietary stem cell capabilities. VCTX210 has gene edits designed to promote immune evasion and cell fitness. The company and ViaCyte are investigating VCTX210 in an ongoing Phase 1 clinical trial that is designed to assess VCTX210’s safety, tolerability, and immune evasion in patients with T1D, and are in the follow-up stage for this clinical trial. The company’s next generation product candidate, VCTX211, is an investigational, allogeneic, gene-edited, stem cell-derived product candidate for the treatment of T1D, which incorporates additional gene edits that aim to further enhance cell fitness. In the fourth quarter of 2022, the Clinical Trial Application for VCTX211 was cleared by Health Canada and the Phase 1/2 clinical trial is ongoing.

In Vivo

In addition to its ex vivo programs, the company is pursuing a number of in vivo gene editing programs. The company’s 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. The company has established a leading platform for in vivo gene disruption, starting in the liver. The company plans to advance a broad portfolio of programs across both rare and common diseases with this platform, starting with cardiovascular diseases, or CVD. The company’s lead investigational in vivo programs, CTX310 and CTX320, target angiopoietin-related protein 3 (ANGPTL3) and lipoprotein(a) (Lp(a)), respectively, two validated targets for CVD. Gene editing has the potential to shift the treatment paradigm for CVD by recapitulating the proven benefit of natural human genetic variants in a single-dose format. In addition, the company continues to develop an expansive whole gene correction platform, starting with using lipid nanoparticles, or LNP, and adeno-associated viral vectors, or AAV, in the liver and advancing to AAV-free, homology-directed repair (HDR)-independent methodologies.

CRISPR-X

While the company has made significant progress with its current portfolio of programs, it recognizes that it needs to continue to innovate to unlock the full potential of CRISPR gene editing and bring the potential of transformative therapies to even more patients. In 2022, the company launched a new early-stage research team known as CRISPR-X that focuses on innovative research to develop next-generation editing modalities. CRISPR-X focuses on technologies to enable whole gene correction and insertion without requiring HDR or viral delivery of DNA, such as all-RNA gene correction, non-viral delivery of DNA and novel gene insertion techniques.

Partnerships

Vertex: The company established its initial collaboration agreement in 2015 with Vertex, which focused on TDT, SCD, cystic fibrosis and select additional indications. In December 2017, the company entered into a joint development and commercialization agreement with Vertex pursuant to which, among other things, it is co-developing and preparing to co-commercialize exa-cel for TDT and SCD. In April 2021, the company and Vertex amended and restated its existing joint development and commercialization agreement, pursuant to which, among other things, it will continue to develop and prepare to commercialize exa-cel for TDT and SCD in partnership with Vertex. The company 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 and myotonic dystrophy type 1.

ViaCyte: The company 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, the company entered into a joint development and commercialization agreement with ViaCyte, or the ViaCyte JDCA. In connection with entering into the ViaCyte JDCA, the company’s existing research collaboration agreement with ViaCyte expired in accordance with its terms. Under the ViaCyte JDCA, the company and ViaCyte are jointly developing and will commercialize product candidates and shared products for use in the treatment of diabetes type 1, diabetes type 2 and insulin dependent/requiring diabetes, or the ViaCyte Collaboration Field, throughout the world. The ViaCyte JDCA includes, among other things, provisions relating to collaboration and program governance, clinical activities for the product candidates and shared products under the agreement and continuing research by the parties in the ViaCyte Collaboration Field. In the third quarter of 2022, Vertex announced it had acquired ViaCyte and the rights to the ViaCyte Collaboration Field.

Bayer: The company entered into an option agreement in the fourth quarter of 2019 with Bayer pursuant to which Bayer has an option to co-develop and co-commercialize two products that it advances for the diagnosis, treatment, or prevention of certain autoimmune disorders, eye disorders, or hemophilia A disorders for a specified period of time, or, under certain circumstances, exclusively license such optioned products.

Other Partnerships: The company has entered into a number of additional collaborations and license agreements to support and complement its hematopoietic stem cell, immuno-oncology, regenerative medicine and in vivo programs and platform, including agreements with: Nkarta, Inc. to co-develop and co-commercialize two donor-derived, gene-edited CAR-NK cell product candidates and a product candidate combining NK and T cells; Capsida Biotherapeutics, Inc. to develop in vivo gene editing therapies delivered with engineered AAV vectors for the treatment of amyotrophic lateral sclerosis and Friedreich’s ataxia; Moffitt Cancer Center and Roswell Park Comprehensive Cancer Center to advance autologous CAR T programs against new targets; MaxCyte, Inc. on ex vivo delivery for its 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 its allogeneic immuno-oncology programs.

Intellectual Property

In-Licensed Intellectual Property from Dr. Charpentier

In April 2014, pursuant to an exclusive license with Dr. Charpentier, the company licensed certain rights to a worldwide patent portfolio which covers various aspects of its gene editing platform technology including, for example, compositions of matter (e.g., CRISPR/Cas9 systems) and methods of use, including the use of CRISPR/Cas9 systems for gene editing. The company refers to this worldwide patent portfolio as the Patent Portfolio. This Patent Portfolio to-date includes, for example, more than ninety-five (95) granted or allowed patents in the United States, the United Kingdom, Canada, Germany, Europe, Japan, China, India, Ukraine, New Zealand, Singapore, Australia, Mexico, Tunisia, Hong Kong, Israel, Peru, the Philippines, and South Africa and pending patent applications in the United States, Europe, Canada, Mexico, Australia and other selected countries in Central America, South America, Asia and Africa. 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.

In addition to Dr. 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. 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. The company refers collectively to Dr. Charpentier, California, and Vienna as the CVC Group. The company is subject to quasi-litigation, inter partes administrative proceedings in the U.S. Patent and Trademark Office, or USPTO, and the European Patent Office involving the Patent Portfolio.

On December 15, 2016, the company entered into a Consent to Assignments, Licensing and Common Ownership and Invention Management Agreement, or the IMA, with California, Vienna, Dr. Charpentier, Intellia Therapeutics, Caribou, ERS Genomics Ltd., or ERS, and its wholly-owned subsidiary TRACR Hematology Ltd., or TRACR. Under the IMA, California and Vienna retroactively consent to Dr. Charpentier’s licensing of her rights to the CRISPR/Cas9 intellectual property, pursuant to its license with Dr. Charpentier, to it, TRACR, and ERS, in the United States and globally.

CRISPR-Owned Intellectual Property

In addition to the Patent Portfolio, the company has a broad intellectual property estate that includes numerous patent families covering key aspects of its CRISPR/Cas9 technologies and development programs which is intended to provide multiple layers of protection. These patent families encompass filings covering the company’s 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 guide RNAs), 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.

Overall, the company’s intellectual property estate includes over one hundred (100) active patent families and over forty (40) granted or allowed patents in the United States, China, Europe, and South Africa, and pending patent applications in the United States, Europe, Australia, Canada, China, Japan, Mexico and other selected countries in Central America, South America, the Middle East, Asia and Africa. The granted patents and any other patents that may ultimately issue from these patent families are expected to expire starting in 2033, not including any applicable patent term extensions.

The company’s U.S. trademark estate consists of over twenty (20) pending applications, including for example, for COBALT, CRISPRX, CRISPR THERAPEUTICS, CRISPR TX, CTX001, CTX130, VCTX210, and VCTX211, as well as seven U.S. registrations, including for CRISPR THERAPEUTICS, the CRISPR THERAPEUTICS logo, and CTX110. The company’s international trademark estate consists of multiple pending applications and registrations, including a pending application for CRISPR THERAPEUTICS in Germany and four registrations in U.K., Italy, Spain and Benelux, and twelve (12) registrations for CRISPR THERAPEUTICS & DESIGN in Brazil, Benelux, Germany, Hong Kong, Italy, South Africa and Spain and three pending applications for COBALT in

Hong Kong and South Africa: The company also has six International Registrations, including for CTX112 designating the EU, Switzerland, and the U.K., CTX131 designating the EU, Switzerland, and the U.K., and CRISPR THERAPEUTICS logo designating Canada, Switzerland, Japan, Korea, Mexico, Russia, Singapore, and the U.K.

Patent Assignment Agreement

In November 2014, the company entered into a patent assignment agreement with Dr. Charpentier, Dr. Ines Fonfara and Vienna, or the Patent Assignment Agreement. Under the Patent Assignment Agreement, Dr. Charpentier, Dr. Fonfara and Vienna assigned to it all rights to a family of patent applications relating to certain compositions of matter, including additional CRISPR/TRACR/Cas9 complexes, and methods of use, including their use in targeting or cutting DNA.

As consideration for the patent rights assigned to it, the company agreed to pay an upfront payment, milestone payments beginning with the filing of a U.S. Investigational New Drug application or its equivalent in another country, a minimum annual royalty, a low single-digit royalty on net sales of products whose manufacture, use, sale, or importation is covered by the assigned patent rights, and a low single-digit percentage of licensing revenues.

The company is 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, including but not limited to an obligation to use commercially reasonable efforts to file a U.S. Investigational New Drug application (or its equivalent in a major market country) by November 2021.

License Agreements

CRISPR License with Dr. Charpentier

In April 2014, the company entered into a license agreement, or the Charpentier License Agreement, with Dr. Charpentier, one of its co-founders, pursuant to which it received an exclusive license under Dr. Charpentier’s joint ownership interest in the Patent Portfolio, to research, develop and commercialize therapeutic products, such as pharmaceuticals or biological preparations, and any associated companion diagnostics, for the treatment or prevention of human diseases, disorders, or conditions, other than hemoglobinopathies, which it refers to as the CRISPR Field. 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. Additionally, the Charpentier License Agreement granted the company an exclusive, worldwide, royalty-free sublicense, including the right to sublicense, to research, develop, produce, commercialize and sell therapeutic products relating to the CRISPR Field which incorporate any intellectual property that TRACR develops under its license with Dr. Charpentier. In turn, the company granted to Dr. Charpentier an exclusive license with the obligation to sublicense to TRACR any intellectual property it develops under the license with Dr. Charpentier for treatment and prevention of hemoglobinopathies in humans, including without limitation, sickle cell disease and thalassemia.

TRACR License with Dr. Charpentier

In April 2014, concurrently with the company’s license agreement with Dr. Charpentier, TRACR entered into a license agreement, or the TRACR License Agreement, with Dr. Charpentier, a minority shareholder of TRACR, under the Patent Portfolio. Pursuant to the TRACR License Agreement, TRACR was granted an exclusive, worldwide, royalty-bearing license, including the right to sublicense, to research, develop, produce, commercialize and sell therapeutic and diagnostic products for the treatment and prevention of hemoglobinopathies in humans, including sickle cell disease and thalassemia, or the TRACR Field. 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. Charpentier. In turn, TRACR granted to Dr. Charpentier an exclusive license to sublicense to CRISPR any intellectual property that TRACR develops under the license with Dr. Charpentier for use in the CRISPR Field.

Enabling Technologies

The company has entered into a number of additional collaborations and license agreements to support and complement its ex vivo and in vivo programs, including agreements related to: technologies to deliver CRISPR/Cas9 ex vivo and in vivo; additions to its hematopoietic stem cell and in vivo programs, including a grant to advance gene editing therapies for HIV; and enhancements to its immuno-oncology and regenerative medicine cell therapy programs and platform. For example, the company has entered into agreements with Nkarta, Inc. to co-develop and co-commercialize two donor-derived, gene-edited CAR-NK cell product candidates and a product candidate combining NK and T cells; Capsida Biotherapeutics, Inc. to develop in vivo gene editing therapies delivered with engineered AAV vectors for the treatment of amyotrophic lateral sclerosis and Friedreich’s ataxia; Moffitt Cancer Center and Roswell Park Comprehensive Cancer Center to advance autologous CAR T programs against new targets; MaxCyte Incorporated on ex vivo delivery for its 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 its allogeneic immuno-oncology programs.

Research and Development

The company’s research and development expenses were $461.6 million for the year ended December 31, 2022.

Government Regulation

In the United States, the company’s product candidates are regulated as biological products, or biologics, under the Public Health Service Act, and the Federal Food, Drug, and Cosmetic Act, and their implementing regulations. In addition to the foregoing, state, and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservation and Recovery Act, and the Toxic Substances Control Act, affect the company’s business.

History

CRISPR Therapeutics AG was founded in 2013. The company was incorporated in 2013 in Switzerland.