On April 29, 2019 Intellia Therapeutics, Inc. (NASDAQ:NTLA), reported that it will present new data, including the first demonstration of targeted gene insertion with CRISPR/Cas9 in the liver of non-human primates (NHPs), at the 22nd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper), taking place April 29-May 2, 2019, in Washington, D.C (Press release, Intellia Therapeutics, APR 29, 2019, View Source [SID1234535545]). Researchers also will present today new in vitro data from Intellia’s lead engineered cell therapy program in acute myeloid leukemia (AML). Later this week at the 2019 ASGCT (Free ASGCT Whitepaper) meeting, Intellia will present new data from its primary hyperoxaluria (PH1) program.
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"The data we are presenting at ASGCT (Free ASGCT Whitepaper) reflects our rapid progress with Intellia’s modular CRISPR/Cas9 platform across a variety of in vivo and engineered cell therapeutic applications," said Intellia President and Chief Executive Officer John Leonard, M.D. "Today’s presentation of our most recent targeted gene insertion data depicts Intellia’s second successful demonstration of CRISPR-mediated gene editing in non-human primates, both in collaboration with Regeneron Pharmaceuticals, Inc. The first was through gene knockout in our transthyretin amyloidosis program and, now, we have used our targeted insertion approach with Factor 9 as a model gene. We also continue to make strides with our collaborators at IRCCS Ospedale San Raffaele toward developing engineered cell therapies for a variety of intractable cancers, such as acute myeloid leukemia."
Intellia’s First Demonstration of Targeted Gene Insertion in NHPs
In a follow-up to Intellia’s presentation at the 2018 European Society of Gene and Cell Therapy (ESGCT) meeting of the first robust demonstration of CRISPR-mediated insertion of transgenes in the liver of mice using Factor 9 (F9) as a model gene, the company will present at ASGCT (Free ASGCT Whitepaper) an advancement of its modular hybrid delivery system, which combines Intellia’s lipid nanoparticle (LNP) platform with an adeno-associated virus (AAV). F9 is a gene that encodes FIX, a blood-clotting protein that is missing or defective in hemophilia B patients.
In a collaboration between Intellia and Regeneron, researchers delivered F9 DNA via a proprietary bi-directional insertion template to demonstrate targeted gene insertion in NHPs, resulting in circulating human FIX protein levels within the normal range of human FIX protein levels (3-5 μg/mL; source: Amiral et al., Clin. Chem., 1984). Researchers observed circulating human FIX protein levels of ~3-4 μg/mL at day 14 after a single dose in an ongoing study, with levels sustained through 28 days (~3-5 μg/mL).
Today, researchers additionally will share updated results from an ongoing durability study, first reported in October, that the circulating supratherapeutic human FIX protein levels achieved in mice with Intellia’s hybrid LNP-AAV delivery system have remained stable through 10 months of observation. Further, researchers will show that they can regulate FIX protein levels in mice by varying LNP doses, AAV doses or insertion site.
Today’s presentation, titled "CRISPR/Cas9-Mediated Targeted Insertion of Human F9 Achieves Therapeutic Circulating Protein Levels in Mice and Non-Human Primates," will be made by Hon-Ren Huang, associate director, Vector Biology, Intellia. This presentation will be accessible through the Events and Presentations page of the Investor Relations section of Intellia’s website at www.intelliatx.com.
Data Update from Intellia’s Acute Myeloid Leukemia Program
Intellia and its research collaborator, IRCCS Ospedale San Raffaele, will provide an update on the company’s lead engineered cell therapy program in AML. Researchers will present new in vitro data showing that CRISPR/Cas9 editing resulted in >98% knockout of the endogenous T cell receptor (TCR), while achieving transfer of various Wilms’ Tumor 1 (WT1)-specific TCRs into >95% of isolated T cells. Researchers generated and tested a library of TCRs with different epitope specificities and human leukocyte antigen (HLA) restrictions, building on the data reported at the 2018 ESGCT meeting. Several lead TCRs restricted to the HLA-A*02:01 allele, a frequently expressed allele in the western hemisphere, show the desired T cell characteristics, including high affinity, epitope specificity and killing of a panel of primary leukemic blast cells that expressed the WT1 antigen.
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.
Today’s presentation, titled "Exploiting Clonal Tracking of WT1-Specific T Cells to Generate a Library of Tumor-Specific T Cell Receptors (TCR), for TCR Gene Editing of Acute Leukemia," will be made by Eliana Ruggiero, Ph.D., Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Italy.
Additional In Vivo Data to be Presented at the 2019 ASGCT (Free ASGCT Whitepaper) Meeting
Intellia’s third oral presentation at the 2019 ASGCT (Free ASGCT Whitepaper) Meeting will take place later this week, on Thur., May 2, 2019. In a presentation titled "CRISPR/Cas9-Mediated Gene Knockout to Address Primary Hyperoxaluria," the company will provide information demonstrating successful independent knockout of two targets of interest, lactate dehydrogenase A (LDHA) and hydroxyacid oxidase 1 (HAO1), to address PH1 in a PH1 mouse model.
The data shows the continued progression of Intellia’s modular platform capability using CRISPR to knock out liver gene targets. The data being presented includes results from an ongoing collaboration with researchers at the University of Alabama at Birmingham.