We expect to dose our first patient with our investigationalIn a research or clinical setting, investigational means that the drug has not been approved or authorized for use in patients outside of a clinical trial by any authority that regulates new treatments, such as the U.S. Food and Drug Administration (FDA) or United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA). genome editingAlso called gene editing. Genome editing collectively refers to a set of technologies, including CRISPR/Cas9, that can be used to cut and modify DNA. Genome editing uses systems to make the DNA change inside the cell. These cells can be edited in the body (in vivo) or outside the body (ex vivo) from a patient or donor. treatment in 2020.
Our modular approach enables us to optimize the power and versatility of the CRISPR/Cas9Adapted from a naturally occurring bacterial immune system, CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats. One of the proteins in the CRISPR system is known as CRISPR-associated 9 protein or Cas9 protein, which acts as a pair of ‘molecular scissors’ to cleave DNA. Researchers have co-opted the bacterial CRISPR/Cas9 system to make specific changes in the DNA of humans, other animals and plants. CRISPR/Cas9 was first harnessed in 2012 as a genome editing tool in the lab. More recently, scientists have begun engineering and testing CRISPR systems to be very specific to a desired genetic target. technology and, importantly, allows us to rapidly develop therapeutics for numerous diseases that currently have limited treatment options.
ATTRAlso known as ATTR. A rare genetic disease caused by accumulation of misfolded transthyretin (TTR) protein, which affects the nerves, heart, kidneys and eyes. Patients can develop amyloidosis by inheriting the faulty TTR gene from a parent (hereditary or hATTR) or due to a natural form of this protein, without genetic mutation (wild-type or wtATTR). NTLA-2001, Intellia’s first investigational therapy, is being evaluated in a Phase 1 clinical trial as a treatment for people who have hereditary ATTR with polyneuropathy. Program:
- NTLA-2001 could be the first curative treatment for transthyretin amyloidosisAlso known as ATTR. A rare genetic disease caused by accumulation of misfolded transthyretin (TTR) protein, which affects the nerves, heart, kidneys and eyes. Patients can develop amyloidosis by inheriting the faulty TTR gene from a parent (hereditary or hATTR) or due to a natural form of this protein, without genetic mutation (wild-type or wtATTR). NTLA-2001, Intellia’s first investigational therapy, is being evaluated in a Phase 1 clinical trial as a treatment for people who have hereditary ATTR with polyneuropathy. (ATTR). By applying the company’s in vivo liver knockoutInactivation/deletion of a DNA sequence using a gene editing technology, such as the CRISPR/Cas9 system. This is the type of gene edit employed by NTLA-2001. approach, NTLA-2001 has the potential for lifelong reduction of TTR proteinAlso known as TTR protein. Produced by the TTR gene. The disease, ATTR, occurs when a specific DNA mutation occurs in the TTR gene that causes the liver to produce the TTR protein in a misfolded form. This misfolded protein can build up in the body and lead to disease-causing nerve and other organ damage. and reversing the disease with a single course of treatment. The investigational therapy is delivered with Intellia’s proprietary non-viral lipid nanoparticleAlso known as LNP. LNPs are fat-based molecules that are the basis of Intellia’s CRISPR/Cas9 delivery platform. In Intellia’s experimental treatments, an LNP delivers to its target gene a simple, two-part genome editing system: the messenger RNA that encodes the Cas9 protein and the guide RNA that can target a specific DNA sequence. platform, which the company is using to develop other in vivo treatments. Our goal is to address hereditary and wild-type ATTR, whether presenting as polyneuropathy or cardiomyopathy, with a single course of treatment.
- ATTR is a progressive and fatal disease that results in systemic failure from the deposition of insoluble TTR proteinAlso known as TTR protein. Produced by the TTR gene. The disease, ATTR, occurs when a specific DNA mutation occurs in the TTR gene that causes the liver to produce the TTR protein in a misfolded form. This misfolded protein can build up in the body and lead to disease-causing nerve and other organ damage. fibrils into multiple organs, leading to diverse disease manifestations and disease progression, including peripheral neuropathy and cardiomyopathy.
- NTLA-2001 is anticipated to be the first systemically delivered investigational CRISPR/Cas9 therapy to enter the clinic. Intellia announced in October 2020 that it had received authorization of its Clinical Trial Application (CTA)Also known as a CTA. Documentation required by regulatory authorities in many countries outside the U.S. seeking authorization to move from preclinical (animal) studies to clinical (human) trials to investigate an experimental treatment. A CTA is considered a regulatory authority equivalent to an Investigational New Drug (IND) application in the U.S. by the United Kingdom Medicines and Healthcare products Regulatory AgencyAlso known as a regulatory agency. The U.S. FDA and the U.K. MHRA are examples of local regulatory authorities responsible for protecting human health. Drug developers like Intellia must seek regulatory approval prior to starting a clinical trial and subsequent product approval. (MHRA) to initiate its Phase 1 study, evaluating NTLA-2001 for the treatment of hereditary transthyretin amyloidosisAlso known as ATTR. A rare genetic disease caused by accumulation of misfolded transthyretin (TTR) protein, which affects the nerves, heart, kidneys and eyes. Patients can develop amyloidosis by inheriting the faulty TTR gene from a parent (hereditary or hATTR) or due to a natural form of this protein, without genetic mutation (wild-type or wtATTR). NTLA-2001, Intellia’s first investigational therapy, is being evaluated in a Phase 1 clinical trial as a treatment for people who have hereditary ATTR with polyneuropathy. with polyneuropathy (hATTR-PN). Intellia is submitting additional regulatory applications in other countries as part of its global clinical development plans.
- In support of NTLA-2001, Intellia completed a 12-month preclinical durabilityUsed to describe gene edits or protein expression sustained over a long period of time. Durability is an important indicator of the permanence of cell, gene and genome editing therapies, specifically the ability to result in a lasting change to the gene edits or effects of the therapy (e.g. protein reduction or protein restoration, depending on the disease). study of its lead lipid nanoparticle (LNP) formulation, which showed maintenance of an average reduction of >95% of serum TTR protein and sustained liver editing after a single dose in non-human primates.
- We lead the development of NTLA-2001, which we are co-developing with Regeneron.
HAE Program:
- NTLA-2002 is Intellia’s development candidate for the treatment of hereditary angioedemaAlso known as HAE. Rare and potentially life-threatening genetic disease characterized by overproduction of bradykinin, which leads to recurring, severe and unpredictable swelling in various parts of the body. (HAE) and is our second in vivo knockout therapeutic candidate. We expect to submit an INDAlso known as an IND or IND application. Companies like Intellia submit an IND to begin testing of investigational therapies in humans in the U.S. An IND is equivalent to a CTA, the regulatory application required in many countries outside the U.S. to begin clinical testing. or IND-equivalent in 2H 2021.
- HAE is a rare genetic disorder characterized by recurring and unpredictable severe swelling attacks in various parts of the body, and is significantly debilitating and disabling. The disease is caused by increased levels of bradykinin, a protein which leads to swelling. NTLA-2002 aims to prevent unregulated production of bradykinin by knocking out the prekallikrein B1 (KLKB1) gene through a single course of treatment to ameliorate the frequency and intensity of these swelling attacks.
- Intellia’s KLKB1 HAE program is subject to an option by Regeneron to enter into a co-development/co-promotion agreement, in which Intellia would remain the lead party.
Hemophilia ASevere, rare genetic bleeding disorders, each caused by a different missing or defective clotting protein. and B Programs:
- In June 2020, Intellia and Regeneron expanded and extended their collaboration to research and develop CRISPR/Cas9-based treatments. Under the terms of two co-development and co-commercialization agreements, Intellia and Regeneron agreed to co-develop potential hemophilia A and B CRISPR/Cas9-based treatments using their jointly owned targeted transgeneA gene introduced into the genome by artificial (e.g. not found in nature) means. To perform targeted gene insertion, a transgene must be delivered to the cell nucleus and once there, fulfill the intended role of the gene, such as restoring protein production or recognizing an immune antigen. insertionInsertion of a new DNA sequence into the genome to manufacture a desired protein using a gene editing technology, such as the CRISPR/Cas9 system. technology. Regeneron is the lead party for both hemophilia A and hemophilia BSevere, rare genetic bleeding disorders, each caused by a different missing or defective clotting protein. development programs.
- These programs build on proprietary innovations developed by Intellia in its collaboration with Regeneron. Data presented in 2019 by Intellia highlighted the promise of Intellia’s technology by demonstrating the first CRISPR-mediated, targeted transgene insertion in the liver of non-human primates, which generated circulating human Factor IX, or FIX, protein at or above normal levels necessary to treat hemophilia BSevere, rare genetic bleeding disorders, each caused by a different missing or defective clotting protein., a severe genetic bleeding disorder. View Press Release
To keep up with our progress, check out our pipeline.