Intellia Therapeutics Presents Preclinical Data Demonstrating Advancements in its Broad Genome Editing Capabilities at the 2021 European Society of Gene & Cell Therapy Annual Congress
- First preclinical data demonstrating Intellia’s allogeneic platform creates immune-evading T cells for therapeutic use in future cancer treatments
- Demonstrated lipid nanoparticle-based delivery as a more efficient multiplex gene editing approach for engineered cell therapies as compared to electroporation
- Achieved durable production of normal human alpha-1 antitrypsin protein levels and reduction of endogenous disease-associated protein in non-human primates for the treatment of liver and/or lung manifestations of alpha-1 antitrypsin deficiency (AATD)
- Platform advances support acceleration of future drug development candidates from both Intellia’s in vivo and ex vivo research portfolio
“Preclinical data presented at ESGCT’s Annual Congress show that using our proprietary genome editing platform, Intellia is able to accomplish multiple CRISPR/Cas9 edits in both in vivo and ex vivo applications, advancing our efforts to develop treatments for challenging genetic diseases like alpha-1 antitrypsin deficiency and to potentially expand both the effectiveness and availability of engineered cell therapies for the treatment of cancer and autoimmune diseases,” said Intellia President and Chief Executive Officer
Proprietary allogeneic solution that can be readily deployed for TCR-T and CAR-T therapy
Key immunological challenges remain unaddressed by allogeneic, or “off-the-shelf”, T cell therapies currently in development for cancer treatment. Leveraging Intellia’s CRISPR/Cas9 platform and an innovative sequential gene editing process, the Company has developed a proprietary allogeneic solution that may avoid the need for long-term or aggressive immunosuppressive regimens and could be readily deployed for TCR-T and CAR-T therapy. The data shared at ESGCT demonstrate that a novel combination of targeted gene edits protected therapeutic T cells from host T cell as well as NK cell-mediated killing in in vitro and in vivo mouse models. Furthermore, these engineered cells showed no impairment in their tumor-killing ability in in vitro assays compared to their autologous counterparts. As part of these efforts, Intellia intends to nominate its first allogeneic cell therapy development candidate by the first half of 2022.
Using lipid nanoparticles to engineer next-generation CRISPR-based cell therapies
Adoptive cell therapies have been successful in certain cancers but have encountered technical and biological barriers, such as reliance on electroporation for editing of T cells, which impacts T cell viability, expansion and gene expression, and can lead to chromosomal translocations when used to introduce multiple simultaneous gene edits. At ESGCT, Intellia presented data demonstrating the use of LNPs to engineer CRISPR-based T cell therapies without the need for electroporation, advancing a robust, modular and scalable platform with the potential to enable future allogeneic and solid tumor therapies requiring multiple genome edits. The data showed that T cells engineered with LNPs showed efficient editing rates, with improved cell properties and performance both in vitro and in vivo, as compared to electroporation. In addition, the lower toxicity associated with LNP delivery allows Intellia’s platform to produce sequentially edited T cells with high efficiency, faster expansion and minimal translocations as compared to electroporation – demonstrated by targeting up to five or more loci (four knockouts and one to two targeted, in-locus insertions). The data support the ability of this platform to be used for a variety of targeting modalities, including CARs and TCRs, to support both autologous or allogeneic T cell candidates, including those requiring multiple edits to address immune rejection and activity in solid or other immune-suppressive tumors. This LNP-based approach is already being used for NTLA-5001, the Company’s first wholly owned ex vivo genome editing candidate, which is in development for acute myeloid leukemia. Intellia expects to initiate patient screening for the Phase 1/2a study of NTLA-5001 by year-end.
Tailored genome editing approach offers potential to independently treat liver and lung manifestations of alpha-1 antitrypsin deficiency (AATD)
New data shared at ESGCT represent the first reported demonstration of consecutive in vivo gene insertion and gene knockout in NHPs. This is an important step toward treating diseases such as AATD, which can manifest as lung disease (due to insufficient functional A1AT protein levels) or liver disease (due to accumulation of mutant A1AT protein) and thus require either inserting a functional gene, removing a disease-associated gene or both. The Company reported data showing that insertion of a healthy form of the SERPINA1 gene, which encodes the A1AT protein, led to normal human A1AT levels in NHPs which were durable through 52 weeks in an ongoing study. Intellia has also now tested the ability to knock out the endogenous cynomolgus SERPINA1 gene while leaving the inserted healthy human version intact. This insertion followed by knockout led to the continued production of normal human levels of functioning A1AT protein -- substantially higher than what has been seen with other treatment approaches -- as well as reduction of the disease-associated protein. Together, these data support the ability of Intellia’s in vivo genome editing platform to address the lung and/or liver manifestations of AATD as needed for a given patient.
Presentations will be available on Intellia’s website at www.intelliatx.com.
About Intellia Therapeutics
This press release contains “forward-looking statements” of
Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events, and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: risks related to Intellia’s ability to protect and maintain its intellectual property position; risks related to Intellia’s relationship with third parties, including its licensors and licensees; risks related to the ability of its licensors to protect and maintain their intellectual property position; uncertainties related to the authorization, initiation and conduct of studies and other development requirements for its product candidates; the risk that any one or more of Intellia’s product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and the risk that Intellia’s collaborations with Regeneron or its other collaborations will not continue or will not be successful. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause Intellia’s actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in Intellia’s most recent quarterly report on Form 10-Q as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the
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Source: Intellia Therapeutics, Inc.