DetailsCategory: DNA RNA and CellsPublished on Thursday, 14 May 2020 10:13Hits: 234

CAMBRIDGE, MA, USA I May 12, 2020 I Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology bothin vivoandex vivo,is presenting three oral presentations and two poster presentations at the 23rd Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT), taking place virtually from May 12-15, 2020. Intellia researchers are presenting new data in support of NTLA-5001, the companys engineered cell therapy candidate for the treatment of acute myeloid leukemia (AML). Intellia is also providing an update on NTLA-2002, its newest development candidate for the treatment of hereditary angioedema (HAE).

At Intellia, we are applying our CRISPR/Cas9 technology to develop new processes that can produce enhanced engineered cell therapies to treat severe cancers, such as AML, that traditional approaches cannot address. Our proprietary platform provides a powerful tool to generate more potent TCR-directed cells, that can treat blood cancers initially and potentially solid tumors. The data being presented today validate Intellias approach of reducing AML tumor cell blasts, and our plans to enter the clinic with NTLA-5001 next year, said Intellia President and CEO John Leonard, M.D. We are also pleased to present data that support our recently announced HAE development candidate, NTLA-2002, Intellias second systemic therapy employing our in vivo knockout approach and modular delivery platform.

Data Presentations on Intellias First Engineered Cell Therapy Development Candidate, NTLA-5001 for the Treatment of AML, and Proprietary Cell Engineering Process

NTLA-5001 is Intellias first engineered T cell receptor (TCR) T cell therapy development candidate, which targets the Wilms Tumor 1 (WT1) intracellular antigen for the treatment of AML. NTLA-5001 is being developed in collaboration with Chiara Boninis team at IRCCS Ospedale San Raffaele to treat AML patients regardless of the genetic subtype of a patients leukemia. AML is a cancer of the blood and bone marrow that is rapidly fatal without immediate treatment and is the most common type of acute leukemia in adults(Source:NIH SEER Cancer Stat Facts: Leukemia AML).

Intellias proprietary process is a significant improvement over standard engineering processes commonly used to introduce nucleic acids into cells. Intellias process enabled multiple gene edits using CRISPR/Cas9, while maintaining cell products with high expansion potential and minimal undesirable chromosomal translocations. CRISPR/Cas9 was used to insert a WT1-directed TCR in locus, while eliminating the expression of the endogenous TCRs, with the goal of producing homogeneous T cell therapies like NTLA-5001.

Intellias novel approach with NTLA-5001 can overcome the challenges of standard T cell therapy, including risks of reduced specificity associated with mixed expression and mispairing of endogenous and transgenic TCRs (tgTCRs); graph-versus-host disease (GvHD) risks, which could lead to an attack on the patients healthy cells; and reduced efficacy tied to lower tgTCR expression per T cell. Intellias unprecedented process is expected to streamline cell engineering and manufacturing, yielding a homogenous product comprising WT1-targeted T cells with high anti-tumor activity. Data highlights from todays presentation include the following:

Intellias cell engineering efforts are focused on its initial clinical investigation of NLTA-5001 on AML, while continuing preclinical studies exploring the potential for targeting WT1 in solid tumors. The company confirmed plans last week to submit an IND or IND-equivalent for NTLA-5001 for the treatment of AML in the first half of 2021.

The presentation titled, Enhanced tgTCR T Cell Product Attributes Through Process Improvement of CRISPR/Cas9 Engineering, will be made today by Aaron Prodeus, Ph.D., senior scientist, Cell Therapy, and can be found here, on the Scientific Publications & Presentations page of Intellias website. These data were a follow-on to the study presented at Keystone Symposias Engineering the Genome Conference from this past February.

In Vivo Data Supports Intellias Novel TCR Candidate

A second presentation on engineered cell therapy progress, in collaboration with IRCCS Ospedale San Raffaele, showed in vivo data demonstrating the potential of TCR-edited T cells to effectively target WT1 tumor cells in AML. In addition to the previously disclosed results of effective in vitro recognition of primary AML tumor cells by edited WT1-specific cytotoxic T cells (CD8 T cells), new data indicate that the selected TCR also enables T helper cells (CD4 T cells) to react to WT1-expressing tumor cells, providing cytokine support. This distinguishes Intellias TCR from other therapeutic TCR candidates, which either exclusively activate toxic CD8 T cells or require the co-transfection of CD8 into CD4 T cells to render them functional.

Using a mouse model carrying disseminated human primary AML, researchers observed a significant therapeutic effect, including decreased AML tumor burden. In addition, no signs of GvHD were observed in mice treated with the WT1-specific T cells. The data show that tgTCR-engineered cells have targeted anti-cancer activity in a challenging model of systemic AML, demonstrating the therapeutic potential of Intellias engineered TCR T cell approach.

The presentation titled, Exploiting CRISPR-Genome Editing and WT1-Specific T Cell Receptors to Redirect T Lymphocytes Against Acute Myeloid Leukemia, will be given today by Eliana Ruggiero, Ph.D., Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS Ospedale San Raffaele, Italy. Notably, ASGCT meeting organizers selected this presentation as one of six to receive the ASGCT Excellence in Research Award this year.

Continued Progress on Intellias Second In Vivo Development Candidate, NTLA-2002 for the Treatment of HAE

Intellia is presenting development data updates on its potential HAE therapy, NTLA-2002, which utilizes the companys systemic in vivo knockout approach, including its proprietary lipid nanoparticle (LNP) system. HAE is a rare genetic disorder characterized by recurring and unpredictable severe swelling attacks in various parts of the body, and is significantly debilitating or even fatal in certain cases. 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.

The KLKB1 gene knockout in an ongoing non-human primate (NHP) study resulted in a sustained 90% reduction in kallikrein activity, a level that translates to a therapeutically meaningful impact on HAE attack rates(Source: Banerji et al., NEJM, 2017). This kallikrein activity reduction was sustained for at least six months, demonstrating the same high level of efficacy and durability seen in earlier rodent studies.

The short talk titled, CRISPR/Cas9-Mediated Gene Knockout of KLKB1 to Treat Hereditary Angioedema, will be given by Jessica Seitzer, director, Genomics, Intellia on Fri., May 15, 2020, when it will be made available here, on the Scientific Publications & Presentations page of Intellias website. The presented data include results from ongoing collaborations with researchers at Regeneron, and the program is subject to an option by Regeneron to enter into a Co/Co agreement, in which Intellia would remain the lead party. Intellia expects to submit an IND or IND-equivalent to initiate a Phase 1 trial for NTLA-2002 in the second half of 2021.

About Intellia Therapeutics

Intellia Therapeuticsis a leading genome editing company focused on developing proprietary, curative therapeutics using the CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology has the potential to transform medicine by permanently editing disease-associated genes in the human body with a single treatment course, and through improved cell therapies that can treat cancer and immunological diseases, or can replace patients diseased cells. The combination of deep scientific, technical and clinical development experience, along with its leading intellectual property portfolio, puts Intellia in a unique position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create a new class of therapeutic products. Learn more aboutIntellia Therapeuticsand CRISPR/Cas9 atintelliatx.comand follow us on Twitter @intelliatweets.

SOURCE: Intellia Therapeutics

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Intellia Therapeutics Reports Progress on CRISPR/Cas9 AML Cancer Therapy Using Proprietary Cell Engineering Process at the 23rd Annual Meeting of the...