Intellia Therapeutics Presents New Data in In Vivo and Ex Vivo Programs at the 26th Annual Congress of the European Society of Gene and Cell Therapy
Intellia scientists present first robust demonstration of CRISPR-mediated insertion of transgenes in the liver
Non-human primate data show high correlation achieved between liver edit and reduction of TTR protein
High rate and specificity of acute myeloid leukemia cell killing observed with genome-edited, WT1-targeting T cells
“We are extremely pleased to present an outstanding compilation of data today reflecting progress in our preclinical genome editing programs,” said Intellia President and Chief Executive Officer
CRISPR-mediated, Targeted Gene Insertion Data
In a collaboration between
Using Intellia’s proprietary bi-directional template, researchers detected hybrid mAlb-hF9 transcripts in >50 percent of hepatocytes following a single dose. Circulating human FIX protein levels of >30,000 ng/mL were achieved, which are predicted to correspond to levels 40-300 times higher than those capable of preventing bleeding episodes in hemophilia B patients, when using a wildtype or hyperfunctional version of F9 (sources: George, et al, NEJM, 2017; Simioni et al, NEJM, 2009). Researchers were able to vary FIX levels by modulating either the LNP or the AAV dose, and expression levels remained stable and ongoing in all cases throughout 12 weeks of observation.
This approach was repeated with Intellia’s wholly owned preclinical in vivo program in alpha-1 antitrypsin deficiency (AATD), another genetic disease of the liver associated with a mutation in the SERPINA1 gene that causes liver and lung dysfunction. Researchers used the LNP-AAV delivery combination of CRISPR/Cas9 components to insert donor template DNA encoding the SERPINA1 gene for AATD. The insertion resulted in blood protein levels in mice that corresponded to a range of SERPINA1 systemic levels required for normal lung function in humans.
Today’s presentation, titled “Supra-therapeutic levels of transgene expression achieved in vivo by CRISPR/Cas9 mediated targeted gene insertion,” was made by
New Non-Human Primate Data from Intellia’s ATTR Program
Intellia also presented new data from non-human primate (NHP) studies in its transthyretin amyloidosis (ATTR) program further demonstrating a high correlation between liver editing and reduction of the transthyretin (TTR) protein. ATTR is a systemic, debilitating and fatal disease caused by one of approximately 136 different inherited mutations in the TTR gene. The company found that a liver editing rate of only ~35-40 percent in NHPs is needed to achieve a therapeutically meaningful reduction of TTR, specifically a TTR protein reduction of >60 percent. The data also demonstrated the transient nature of Intellia’s proprietary modular LNP delivery system, which was rapidly cleared from circulation, with all CRISPR/Cas9 components undetectable within five days of administration. Furthermore, rates of editing were durable over a six-month period without re-dosing the animals.
These data included results from ongoing collaborations with researchers at Regeneron and the
Data Update from Intellia’s Acute Myeloid Leukemia Program
In a presentation titled “Hunting novel WT1-specific T cell receptors for immune gene therapy of acute myeloid leukemia,” Intellia and its research collaborator, OSR, led by
Intellia and OSR are collaborating to develop best-in-class CRISPR-edited T cells directed to a specific epitope of WT1, a tumor-associated antigen overexpressed across a wide range of different tumor types and a known driver of leukocyte blasts in hematological cancers. Intellia’s first cell therapy tumor target is WT1 for the treatment of AML and other potential hematological malignancies, as well as for solid tumors.
This press release contains “forward-looking statements” of
Any forward-looking statements in this presentation 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 our intellectual property position; risks related to the ability of our licensors to protect and maintain their intellectual property position; uncertainties related to the initiation and conduct of studies and other development requirements for our 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 will not be predictive of future results in connection with future studies; and the risk that Intellia’s collaborations with Novartis or Regeneron or its other ex vivo 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 annual report on Form 10-K and quarterly reports on Form 10-Q filed with the Securities and Exchange Commission, as well as discussions of potential risks, uncertainties, and other important factors in Intellia’s other filings with the Securities and Exchange Commission. All information in this presentation is as of the date of the release, and Intellia Therapeutics undertakes no duty to update this information unless required by law.
Senior Vice President
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Source: Intellia Therapeutics, Inc.