Intellia Therapeutics Stock

Intellia Therapeutics, Inc. is a leading clinical-stage gene editing company. The company focuses on developing potentially curative therapeutics using CRISPR/Cas9-based technologies. CRISPR/Cas9, an acronym for Clustered, Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated 9 (Cas9), is a technology for genome editing, the process of altering selected sequences of genomic deoxyribonucleic acid (DNA).

To fully realize the transformative potential of CRISPR/Cas9-based technologies, the company is building a full-spectrum gene editing company, by leveraging its modular platform, to advance in vivo and ex vivo therapies for diseases with high unmet need by pursuing two primary approaches. For in vivo applications to address genetic diseases, it deploys CRISPR/Cas9 as the therapy. The company's in vivo programs use CRISPR/Cas9 to enable precise editing of disease-causing genes directly inside the human body. In addition, the company is advancing ex vivo applications to address immuno-oncology and autoimmune diseases, where it uses CRISPR/Cas9 as the tool to create the engineered cell therapy. For its ex vivo programs, CRISPR/Cas9 is used to engineer human cells outside the body. The company's deep scientific, technical and clinical development experience, along with its robust intellectual property (IP) portfolio, has enabled it to unlock broad therapeutic applications of CRISPR/ Cas9 and related technologies to create new classes of genetic medicine.

The company continues to advance its platform's modular solutions and research efforts on genome editing technologies, as well as delivery and cell engineering capabilities to generate additional development candidates. The company's lead in vivo candidates, NTLA-2001 for the treatment of transthyretin (ATTR) amyloidosis and NTLA-2002 for the treatment of hereditary angioedema (HAE), are the first CRISPR/Cas9-based therapy candidates to be administered systemically, via intravenous (IV) infusion, for precision editing of a gene in a target tissue in humans. In addition, the company is advancing multiple ex vivo programs, wholly owned and in collaboration with partners, for the treatment of immuno-oncology and autoimmune diseases.

Strategy

The key elements of the company's strategy are to develop potentially curative CRISPR/Cas9-based medicines; advance its science; be the best place to make therapies; and focus on long-term sustainability. The company's strategy is to advance its full-spectrum gene editing company, focused on developing and commercializing curative CRISPR/Cas9-based therapeutics, by leveraging its modular platforms. The key elements of the company's strategy include focusing on indications that enable it to fully develop the potential of the CRISPR/Cas9 System; aggressively pursuing in vivo liver indications to develop therapeutics with its proprietary delivery system; progressing ex vivo therapeutic programs; continuing to leverage strategic partnerships to accelerate clinical development; and growing its leadership position in the field of genome editing.

Pipeline

In Vivo Programs

The company's selection criteria include identifying diseases that originate in the liver; have well-defined mutations that can be addressed by a knockout or insertion approach; have readily measurable therapeutic endpoints with observable clinical responses; and for which effective treatments are absent, limited or unduly burdensome. The company's initial in vivo indications target genetic liver diseases, including its ATTR amyloidosis, HAE and AATD development programs. The company's efforts on in vivo delivery focus on the use of LNPs for delivery of the CRISPR/Cas9 complex to the liver.

NTLA-2001 is the first investigational CRISPR-based therapy to be systemically delivered to edit a target gene inside the human body. NTLA-2001 has the potential to become the first single-dose treatment for ATTR amyloidosis. It is designed to inactivate the TTR gene that encodes for the TTR protein.

In November 2023, the company announced new positive interim data from the Phase 1 study of NTLA-2001. Updated data from over 60 patients showed consistent, deep, and durable serum TTR reduction was achieved with a single dose of NTLA-2001, including in 29 patients who reached 12 months or more of follow-up as of the data cutoff date of May 11, 2023. Across all patients who received a dose of 0.3 mg/kg or higher (n=62), the median serum TTR reduction was 91% and the median absolute residual serum TTR concentration was 17 ug/mL at day 28. Across all patients and at all dose levels tested, NTLA-2001 was generally well tolerated, and the majority of adverse events were mild in severity. These interim data were presented at the 4th International ATTR Amyloidosis Meeting, held in Madrid, Spain. The company plans to present updated data from the ongoing Phase 1 study in 2024.

NTLA-2001 has received orphan drug designation for the treatment of ATTR amyloidosis by both the European Commission (EC) and the U.S. Food and Drug Administration (FDA). NTLA-2001 is the subject of a co-development and co-promotion (Co/Co) arrangement directed to the company's first collaboration target with Regeneron, ATTR (the ATTR Co/Co), for which it is the clinical and commercial lead party and Regeneron is the participating party.

Hereditary Angioedema (HAE) Program

NTLA-2002 is the company's wholly owned candidate for the treatment of HAE. NTLA-2002 is designed to knock out the kallikrein B1 (KLKB1) gene in the liver, with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of HAE. This investigational approach aims to prevent attacks for people living with HAE by providing continuous reduction of plasma kallikrein activity following a single dose.

The company's multi-national Phase 1/2 study is evaluating the safety, tolerability, activity, pharmacokinetics and pharmacodynamics of NTLA-2002 in adults with Type I or Type II HAE. This includes the measurement of kallikrein protein levels and activity, as well as HAE attack rate. The Phase 1 portion of the study was an open-label, single-ascending dose design. Two dose levels of NTLA-2002 were identified from Phase 1 for further evaluation in the Phase 2, randomized, placebo-controlled portion of the study.

In January 2024, the company announced that enrollment and dosing was completed in the Phase 2 portion of the study. Data from the Phase 2 study will inform the dose of NTLA-2002 selected for the pivotal Phase 3 study. The company expects to initiate the global pivotal Phase 3 study, including U.S. patients, in the second half of 2024, subject to regulatory feedback.

In January 2024, the company also announced that positive interim results from the Phase 1 portion of the Phase 1/2 study were published in the New England Journal of Medicine. These results were first reported in June 2023 at the European Academy of Allergy and Clinical Immunology Hybrid Congress. Across all ten patients, a 95% mean reduction in monthly attack rate was observed after a single dose of NTLA-2002 through the latest follow-up. The median duration of follow-up was 9.0 months (range of 5.6 - 14.1 months). At all three dose levels evaluated in the Phase 1 portion of the study, NTLA-2002 was well tolerated, and the most frequent adverse events reported were mild, transient infusion-related reactions and fatigue. The company plans to present updated data from the Phase 1 and new data from the Phase 2 portion of the study in 2024.

The company has received five regulatory designations for NTLA-2002, including orphan designation in the European Union (EU) granted by the EC in November 2023. NTLA-2002 was also granted orphan designation and Regenerative Medicine Advanced Therapy (RMAT) designation by the FDA, the Innovation Passport by the United Kingdom (U.K.) Medicines and Healthcare products Regulatory Agency (MHRA), as well as access to the Priority Medicine (PRIME) program by the European Medicines Agency (EMA). Access to the PRIME program is granted by the EMA to drug candidates that may offer a major therapeutic advantage over existing treatments or that benefit patients without treatment options.

Alpha-1 Antitrypsin Deficiency (AATD) Program

NTLA-3001 is the company's wholly owned, first-in-class CRISPR-mediated in vivo targeted gene insertion development candidate for the treatment of AATD-associated lung disease. It is designed to precisely insert a healthy copy of the SERPINA1 gene, which encodes the A1AT protein, with the potential to restore permanent expression of functional A1AT protein to therapeutic levels after a single dose. The company's approach seeks to improve patient outcomes, including eliminating the need for weekly IV infusions of A1AT augmentation therapy or lung transplant in severe cases. In December 2023, the company submitted a clinical trial application (CTA) to initiate a first-in-human, Phase 1 study of NTLA-3001 and plan to dose the first patient in 2024.

In Vivo Research Programs

The company continues to work on various liver-focused programs, such as hemophilia A and hemophilia B, which it is co-developing with Regeneron, as well as other liver targets, which it is working on both independently and in partnership with Regeneron, that would leverage its wide-ranging gene editing capabilities to knockout, insert and make consecutive edits to the genome.

The company is further advancing editing and delivery strategies to expand the reach of CRISPR-based gene editing to tissues outside of the liver. For example, the company has presented preclinical data establishing proof-of-concept for non-viral genome editing of bone marrow and hematopoietic stem cells (HSCs) in mice. This represented the company's first demonstration of systemic in vivo genome editing in bone marrow using its proprietary non-viral delivery platform. In September 2023, the company entered into an expanded research collaboration with Regeneron to develop additional in vivo CRISPR-based gene editing therapies focused on neurological and muscular diseases. In addition, the company is collaborating with SparingVision to develop novel genomic medicines utilizing CRISPR/Cas9 technology for the treatment of ocular diseases.

Ex Vivo Programs

The company is advancing multiple preclinical programs, wholly owned and in collaboration with partners, utilizing its allogeneic platform for the treatment of immuno-oncology and autoimmune diseases. The company's proprietary allogeneic cell engineering platform is designed to avoid both T cell- and NK cell-mediated rejection, a key unsolved challenge with other investigational allogeneic approaches.

The company is developing allogeneic cellular therapies, which are cells derived from unrelated donors and modified outside of the human body to allow them to be administered to an unrelated patient. These allogeneic cellular therapies could be used to treat both oncological and immunological diseases. The company's proprietary technologies, including its LNP-based cell engineering platform and novel allogeneic solution, are designed to offer significant advantages over both autologous cell therapies and allogeneic approaches being investigated by others. Preclinical data presented on the company's differentiated allogeneic engineering platform showed allogeneic T cells were shielded from immune rejection, both host T and NK cell attack.

The company is advancing engineered CAR and TCR cells as immuno-oncological therapies.

In addition, the company strategically partner with others who possess complementary capabilities or technologies to bring forth innovative engineered cell therapy candidates outside of its core areas of focus. This includes collaborations with AvenCell and Kyverna, who are leveraging the company's ex vivo allogeneic cell engineering platform to develop novel CAR-T cell therapy candidates for a variety of therapeutic indications, as well as ONK to advance CRISPR-edited NK cell therapy candidates.

Ex Vivo Research Programs

The company is researching engineered cell therapies to treat a range of hematological and solid tumors. The company is pursuing modalities, such as TCRs and CARs, with broad potential in multiple indications. The company is advancing efforts for allogeneic therapies to move from liquid to solid tumors. The company's researchers are developing and improving cell-engineering manufacturing and delivery processes that may allow it to deliver T cell therapies with high levels of editing, robust levels of cell expansion, desirable memory phenotypes, improved function and no translocations above background levels.

The company's proprietary T cell engineering process using LNPs to engineer cell therapies enables multiple, sequential gene edits. The company has shared preclinical data demonstrating that its LNP-based engineering technology is a significant improvement over electroporation, the standard engineering process used to introduce proteins and nucleic acids into cells. The resulting T cells engineered with LNPs had improved cell properties and performance both in vitro and in vivo as compared to electroporation. The data support the ability of the company's platform to be used for a variety of targeting modalities, including CARs and TCRs, and to support both autologous and allogeneic T cell candidates. The LNP-based approach has been used in multiple ex vivo candidates in development by the company and its collaborators.

The company's proprietary allogeneic solution to create engineered T cells with high anti-tumor activity may be uniquely capable of persisting in the patient to maintain durable responses. Notably, a novel combination of gene edits, including knockout of specific human leukocyte antigen (HLA) Class II and some HLA proteins while retaining other HLA proteins, yielded T cells capable of avoiding rejection by host T and NK cells in preclinical models. With its approach, the company is able to pursue a simplified HLA matching strategy between healthy donor T cells and recipient patients, allowing for the development of an off-the-shelf therapy that addresses the majority of the patient population with only a small set of donors. The company's allogeneic platform is being deployed for investigational TCR-T and CAR-T cell therapies.

The company's genome editing capabilities include a novel, proprietary cytosine deaminase base editor technology. The company has demonstrated the technology's potential for enhanced cell engineering, with multiple simultaneous gene knockouts achieving >90% T cell editing efficiency and no detectable increase in translocation above background levels.

Genome-Editing Platform

The company's robust genome-editing platform forms the foundation of its full-spectrum therapeutic product pipeline based on CRISPR/Cas9 and derivative technologies. The company's modular platform is based on its proprietary components that can serve both in vivo and ex vivo programs, as well as its delivery technologies that can be used in either program type. In addition to the components, the company has developed robust, high volume (high throughput) capabilities centering around enabling strategic target identification and validation that will provide it with a competitive advantage in creating successful therapeutic products.

The company is committed to staying at the forefront of the genome editing revolution and will continue to advance its technology platform through a mix of both internal research and development and external opportunities in order to potentially serve more patients across a broad set of diseases. With proprietary CRISPR/Cas9-based technology at the core of its platform, the company has built a comprehensive set of editing and delivery tools to expand its current solutions for therapeutic application. These additions include the company's proprietary base editor, as well as novel CRISPR-derivative enzymes, which provide it with the capabilities to achieve multiple editing strategies.

The company has built a high throughput, scalable data processing and analysis, or informatics, infrastructure to support various aspects of its platform, including gRNA selection and evaluation of on- and off-target editing in cells. Depending on the desired editing strategy, the company uses proprietary bioinformatics methods to design candidate guides and select those that are both highly specific and has high cutting efficiency. As it grows the company's experimental data set, it continues to incorporate gRNA performance into its algorithms to improve their predictive power.

As part of the process to identify gRNAs for potential development candidates, the company screens numerous gRNAs for their ability to generate the required edit at the genomic site of interest, called on-target activity, as well as any potential propensity to generate unwanted events at other sites in the genome, also known as off-target activity. To evaluate on-target activity, the company uses high throughput sequencing methods to analyze the genomes of edited cells, allowing it to assess overall editing efficiency and to examine the nature of the editing events, such as specific insertions or deletions.

For gRNAs selected through its primary on-target screens, the company performs a variety of analyses to look for possible off-target editing events, including bioinformatic evaluations and experimental methods. Part of the company's approach involves identifying candidates with no or few off-target sites based on experimental measurements of genome-wide DNA breaks, as well as targeted sequencing of such candidate sites to evaluate actual off-target editing events in relevant cell types. The company continues to optimize its gRNA qualification capability over time by increasing its throughput, improving its off-target activity detection accuracy and increasing its bioinformatics predictive accuracy.

CRISPR/Cas9 systems can function with gRNAs having a variety of modifications, such as changes to the gRNA sequence or chemical modifications of nucleotides. As part of its development of CRISPR/Cas9 therapeutics, the company has engineered modified gRNAs to, for example, improve editing efficiency, specificity and stability inside cells, as well as to reduce the likelihood of an immune response. The company's work in this area will allow it to develop the most appropriate gRNAs for therapeutic applications.

The company's current preferred Cas9 protein is derived from a species of bacteria called S. pyogenes (Spy), which is the Cas9 used in the vast majority of published CRISPR/Cas9 literature to date. The company is exploring other naturally occurring Cas9 proteins and nucleases from other bacteria, which may differ from Spy Cas9 in aspects such as specificity, size or mechanism of DNA recognition, binding and cutting. The company is pursuing these alternative Cas9 forms and other nucleases through ongoing internal work, collaborations with its existing partners and scientific founders, and in-licensing opportunities. The company is investigating targeted modifications of Cas9 that can modulate DNA activity by mechanisms other than cleavage.

In February 2024, Regeneron and the company announced the clearance by the FDA of an investigational new drug (IND) application to initiate a clinical trial for the company's investigational in vivo CRISPR-based F9 gene insertion program for people living with hemophilia B. A Phase 1, first-in-human study is expected to begin in mid-2024. Regeneron leads development and commercialization of hemophilia A and B programs in collaboration with it.

The company's DNA writing technology may enable a range of precise editing strategies. These strategies include targeted corrections, insertions, deletions, and the full range of single-nucleotide changes, which could provide new ways to edit disease-causing genes and broaden the therapeutic potential for genomic medicines.

The company focuses its initial in vivo applications in the liver, where it delivers the CRISPR/Cas9 therapy intravenously to patients using its proprietary LNP platform.

The company's proprietary LNPs encapsulate the therapeutic cargo, providing it with stability, selective delivery, improved pharmacologic properties and controlled circulation time. The company's therapeutic cargo is designed to degrade relatively quickly, resulting in transient expression of Cas9. The company sees multiple advantages of using LNPs as an in vivo delivery vehicle, particularly as optimized by it for delivery of the CRISPR/Cas9 system or its components. First, LNPs have been clinically validated as an effective delivery vehicle of therapeutic nucleic acids to the liver after IV administration. LNPs have shown to have favorable tolerability in humans, with toxicities being dose-dependent, monitorable and reversible. Additionally, LNPs are chemically well-defined and have a completely synthetic route of manufacture, which permits greater scalability, product quality and controls. LNPs are tunable, do not exhibit cargo size limitations and can co-formulate different nucleic acid components, such as messenger RNA and gRNAs. There is no pre-existing immunity to the LNP or limiting de novo immunity after dosing, allowing for repeat dosing as required by the therapeutic approach. The company is advancing its programs using its proprietary LNP delivery system, which uses a set of biodegradable, well-tolerated lipids, based on lipids originally developed by Novartis Institutes for BioMedical Research, Inc. (Novartis) and in-licensed by it for use with all genome editing technologies, including CRISPR/Cas9 products. As of December 31, 2023, the company had successfully demonstrated well-tolerated in vivo editing in various animal models, including in mouse, rat and NHP livers, with a single dose of systemically delivered LNPs. In addition, the company has moved into late-stage human clinical trials using LNPs as the delivery mechanism. Based on interim data reported from the first-in-human study of NTLA-2001, the company has also successfully demonstrated that LNP delivery of CRISPR/Cas9 is well-tolerated in humans.

The company plans to continue to further improve on its LNP system to optimize delivery of a variety of CRISPR/Cas9 therapeutic components, including templates for repair and insertion edits. In parallel, the company is exploring additional delivery vehicles, including synthetic particles and viral vectors. The company is developing delivery strategies that will allow it to target other tissues.

The company has developed a proprietary allogeneic cell engineering platform to overcome one of the key challenges to current allogeneic approaches employed by others, which is host rejection of the adoptive cell therapy. In preclinical studies, the company's allogeneic technology demonstrated the ability to create T cells with high anti-tumor activity capable of avoiding host T and NK cells, and thereby persisting to maintain durable responses. The company's proprietary approach leverages a novel combination of sequential edits, including knockout of HLA Class II and HLA-A while retaining HLA-B and HLA-C proteins. With its approach, the company can pursue a simplified HLA matching strategy between healthy donor T cells and recipient patients, allowing for the development of an off-the-shelf therapy that addresses the majority of the patient population with only a small set of donors. The company's allogeneic platform is being deployed for investigational TCR-T and CAR-T cell therapies.

Collaborations and Other Arrangements

Regeneron Pharmaceuticals, Inc. (Regeneron)

The company has a license and collaboration agreement with Regeneron (as amended from time to time, the 2016 Regeneron Agreement). The 2016 Regeneron Agreement has two principal components a product development component under which the parties will research, develop and commercialize CRISPR/Cas-based therapeutic products primarily focused on genome editing in the liver; and a technology collaboration component, pursuant to which it and Regeneron will engage in research-related activities aimed at discovering and developing novel technologies and improvements to CRISPR/Cas technology to enhance its genome editing platform.

The company also has entered into three co-development and co-funding agreements with Regeneron, specifically the ATTR Co/Co and co-development and co-funding agreements for the treatment of hemophilia A and hemophilia B (the Hemophilia Co/Co) agreements.

SparingVision SAS (SparingVision)

In 2021, the company entered into a license and collaboration agreement with SparingVision, a genomic medicine company developing vision saving treatments for ocular diseases, to develop novel genomic medicines utilizing CRISPR/Cas9 technology for the treatment of ocular diseases. The company granted SparingVision exclusive rights to its proprietary in vivo CRISPR/Cas9-based genome editing technology for up to three ocular targets addressing diseases with significant unmet medical need. In addition, the parties are collaborating to research and develop novel self-inactivating AAV vectors and LNP-based product candidates to address delivery of CRISPR/Cas9 genome editing reagents to the retina.

Kyverna Therapeutics, Inc. (Kyverna)

In 2021, the company entered into a licensing and collaboration agreement with Kyverna, a cell therapy company engineering a new class of therapies for autoimmune and inflammatory diseases, for the development of an allogeneic CD19 CAR-T cell therapy for the treatment of a variety of B cell-mediated autoimmune diseases. The company granted Kyverna rights to its proprietary ex vivo CRISPR/Cas9-based allogeneic platform for the development of KYV-201, an allogeneic CD19 CAR-T cell investigational candidate for the treatment of select autoimmune diseases. Kyverna will lead and fund preclinical and clinical development for KYV-201 and the company will be eligible to receive certain development and commercial milestone payments, as well as low-to-mid-single-digit royalties on potential future sales.

ONK Therapeutics, Ltd (ONK)

In February 2022, the company announced a license, collaboration and option agreement with ONK for the development of engineered NK cell therapies to cure patients with cancer. The agreement grants ONK a non-exclusive license to the company's proprietary ex vivo CRISPR/Cas9-based genome editing platform and its LNP-based delivery technologies for the development of up to five allogeneic NK cell therapies.

ReCode Therapeutics, Inc. (ReCode)

On February 15, 2024, the company announced a strategic collaboration with ReCode Therapeutics, Inc. (ReCode), a clinical-stage genetic medicines company, to develop novel genomic medicines for the treatment of cystic fibrosis (CF). CF is a genetic disease caused by mutations in the CFTR gene, leading to the accumulation of thick mucus in the lungs, digestive systems and other organs. CF can result in life-threatening infections, respiratory failure and other serious complications.

Intellectual Property

The company's licensed patent portfolio encompasses foundational filings on the use of CRISPR/Cas9 systems for genome editing, improvement modifications of these CRISPR systems, including base editor and DNA writing technologies, LNP technologies, TCRs for specific targets, and cell expansion technology relevant to stem cell-based therapies. The company accesses these patent estates from licensors, including Caribou Biosciences, Inc. (Caribou) and others.

In addition to its in-licensed IP, the company's IP portfolio includes over 70 patent families filed since 2015 covering solely or jointly owned technologies that it has developed independently or through its collaboration with Regeneron. The patent families claim inventions relating to CRISPR/Cas9 improvements, methods for delivering CRISPR/Cas9 complexes, methods of treating diseases using CRISPR/Cas9 genome editing, and methods for analyzing editing events, among others. Patents resulting from the company's internal portfolio, if issued, would expire no earlier than 2036.

Caribou Biosciences In-Licensed Intellectual Property (Caribou)

In 2014, the company entered into a license agreement with Caribou (the Caribou License), as subsequently amended and supplemented, for an exclusive, worldwide license for human therapeutic, prophylactic, and palliative uses, except for anti-fungal and anti-microbial uses, defined in the license agreement as its field of use, of any CRISPR/Cas9-related patents and applications owned, controlled or licensed by Caribou, as well as companion diagnostics to its product or product candidates.

The licensed Caribou patent portfolio includes several U.S. and foreign patents and patent applications owned or licensed by Caribou, including over 50 patent applications in the U.S. and internationally, related to the CRISPR/Cas platform and an exclusive sublicense in the company's field of use to the Regents of the University of California (UC) and University of Vienna's (Vienna) rights in U.S. and foreign patents and patent applications covering the CRISPR/Cas9 technology, which they co-own with Dr. Emmanuelle Charpentier (collectively, the UC/Vienna/Charpentier IP). In 2015, the company exercised its option to include in the licensed Caribou patent portfolio the U.S. and foreign patent and patent applications owned or controlled by Pioneer Hi-Bred International (Pioneer) and its affiliates. The company has the right to grant sublicenses to the licensed Caribou patent portfolio to third parties in its field of use. Caribou retains the right to practice the licensed IP in all other fields, including for its own specific therapeutic product candidates outside its field of use. The UC/Vienna/Charpentier IP and Pioneer IP, and its rights to the same.

In June 2021, the company executed a Leaseback Agreement (Leaseback) with Caribou, concluding an arbitration between it and Caribou in which an arbitration panel found that Caribou had violated the terms of the Caribou License.

The Regents of the University of California and the University of Vienna Intellectual Property

The UC/Vienna/Charpentier IP covers methods of use and compositions relating to engineered CRISPR/Cas9 systems for, among other things, cleaving or editing DNA and altering gene product expression in various organisms, including humans. The earliest claimed priority date for the patents in the UC/Vienna/Charpentier IP is May 25, 2012. As of December 31, 2023, this family included over 50 issued patents in the U.S. and over 30 granted patents outside the U.S., including for example the U.K., Australia, China, Japan, Israel, Mexico and the approximately 40 countries that are members of the European Patent Convention. Applications continue to be prosecuted in the United States Patent and Trademark Office (USPTO) and other patent agencies across the world. Patents issued from this family will expire in or after 2033, if successfully maintained.

In April 2013, Caribou entered into an exclusive, worldwide license in all fields, with the right to sublicense, for this patent family with UC/Vienna solely under UC/Vienna ownership rights. Caribou's license remains in effect for the life of the last-to-expire patent or last-to-be-abandoned patent application licensed, whichever is later. Through its license agreement with Caribou, the company has an exclusive sublicense to UC/Vienna's interest in this foundational CRISPR/Cas9 patent family for use in human therapeutics, except for anti-fungal and anti-microbial uses as defined in the license agreement as its field of use.

On June 25, 2019, the USPTO's Patent Trial and Appeal Board (the PTAB) declared another interference between the UC/Vienna/Charpentier and certain patents issued to the Broad Institute, Massachusetts Institute of Technology, and the President and Fellows of Harvard College (collectively, the Broad Institute patent family or the Broad), which claim aspects of CRISPR/Cas9 systems and methods to edit genes in eukaryotic cells, including human cells.

In addition, the PTAB has instituted and completed the motions phase in interferences between the same 14 allowable patent applications in the UC/Vienna/Charpentier portfolio, and certain patent rights owned by ToolGen, Inc. (ToolGen), and certain patent rights owned by Sigma-Aldrich Co. LLC, a Merck KGaA subsidiary (Sigma-Aldrich). In both interferences, ToolGen and Sigma-Aldrich, respectively, purport that their patent rights cover the use of CRISPR/Cas9 for gene editing in eukaryotic cells.

Pioneer Hi-Bred International (DuPont Company) Intellectual Property

Pioneer, including the DuPont Company, have licensed to Caribou on a worldwide basis, various patent families relating to CRISPR/Cas systems, components and methods of use generally and CRISPR/Cas9 specifically in certain fields, which include the company's field of use under the company's license agreement with Caribou. In July 2015, the company exercised its option under the license agreement with Caribou to sublicense these Pioneer patent families in its field of use. The license from Pioneer to Caribou will expire upon the expiration, abandonment or invalidation of the last patent or patent application licensed from Pioneer to Caribou.

Competition

Specific to its NTLA-2001 program, the company is aware of other companies that are commercializing or developing products and therapies used to treat ATTR amyloidosis, including Alnylam Pharmaceuticals, Inc., AstraZeneca Pharmaceuticals LP, BridgeBio Pharma Inc., Ionis Pharmaceuticals, Inc., Metagenomi Technologies, LLC, Novo Nordisk A/S and Pfizer, Inc.

Specific to its NTLA-2002 program, the company is aware of other companies that are commercializing or developing products used to treat HAE, including ADARx Therapeutics, Inc., Astria Therapeutics Inc., BioCryst Pharmaceuticals Inc., BioMarin Pharmaceutical Inc., CSL Limited, Ionis Pharmaceuticals, Inc., KalVista Pharmaceuticals, Inc., Pharming Group N.V., Pharvaris N.V. and Takeda Pharmaceutical Company Limited.

The company is also aware of companies developing therapies in various areas related to its specific research and development programs. For ex vivo, these companies include Allogene Therapeutics, Inc., Cellectis S.A., CRISPR Therapeutics AG and Precision BioSciences, Inc. For in vivo, these companies include CRISPR Therapeutics AG, Editas Medicine, Inc., Excision Biotherapeutics, Inc., Locus Biosciences, Inc., Metagenomi Technologies, LLC, Precision Biosciences, Inc. and Verve Therapeutics Inc.

Research and Development

The company's research and development expenses included $435.1 million during the year ended December 31, 2023.

Government Regulation and Product Approval

Before clinical testing of biological products in the U.S. may begin, the company must submit an IND application to the FDA, which reviews the clinical protocol and other information, and the IND application must become effective before clinical trials may begin. Prior to initiating clinical trials in foreign countries, clinical trial applications (CTAs) or other equivalent applications, similar to IND applications, must be approved. In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, all affect the company's business.

History

Intellia Therapeutics, Inc. was founded in 2014. The company was incorporated under the laws of the state of Delaware in 2014.