Specific and potent tumor cell killing observed in WT1-positive acute myeloid leukemia blasts in vitro by TCR-based engineered T cells, supporting Intellia’s first engineered T cell therapy development candidate, NTLA-5001





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CAMBRIDGE, Mass., Feb. 10, 2020 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NTLA), a leading genome editing company focused on developing curative therapeutics using CRISPR/Cas9 technology both in vivo and ex vivo, is presenting new data from two of its development programs at Keystone Symposia’s Engineering the Genome Conference, a joint meeting with the Emerging Cellular Therapies: Cancer and Beyond Conference, taking place Feb. 8-12, 2020, in Banff, Canada. Intellia researchers are presenting data in support of the company’s lead engineered cell therapy development candidate, NTLA-5001 for the treatment of the hematological cancer, acute myeloid leukemia (AML). Intellia also is sharing preclinical results for its hereditary angioedema (HAE) program, which is Intellia’s third CRISPR/Cas9 development program, announced in January 2020.

“Intellia continues to demonstrate strong progress across both our engineered cell therapy and in vivo pipelines,” said Intellia President and Chief Executive Officer John Leonard, M.D. “We are observing very favorable preclinical data with our engineered T cells, and we are moving ahead with IND-enabling studies and manufacturing for NTLA-5001, to enable a regulatory submission in the first half of 2021.

“On the in vivo side, the data from our HAE development program reinforce the modularity of Intellia's non-viral delivery genome editing platform and how it is enabling independent, single-dose therapies for multiple monogenic diseases. For HAE, we expect to nominate a development candidate in the first half of this year,” continued Dr. Leonard.

New Data from Intellia’s Engineered Cell Therapy Development Program for AML

NTLA-5001, which is Intellia’s first engineered T cell therapy development candidate and is wholly owned, utilizes a T cell receptor (TCR)-directed approach to target the Wilms’ Tumor 1 (WT1) intracellular antigen for the treatment of AML. The company’s WT1-TCR T cell approach aims to develop a broadly applicable treatment for AML patients, regardless of mutational background of a patient’s leukemia.

The company is presenting data demonstrating that the selection of a natural, high-affinity TCR, in combination with CRISPR-enabled engineering and targeted insertion, results in an engineered T cell capable of specific and potent killing of primary AML blasts. Today’s presentation at Keystone builds on data previously presented last fall at the Annual Congress of the European Society of Gene and Cell Therapy (ESGCT).

The data being presented at the Keystone conference substantiate the advantages that a homogeneous T cell product developed through CRISPR engineering, like NTLA-5001, may have over traditional T cell engineering approaches. In particular, traditional T cell engineering methods typically result in a T cell product that carries two different TCRs, one endogenous and one transferred, which can pair in various combinations of alpha and beta chains and form mixed TCRs with unknown specificities. Intellia researchers are sharing today that the precise replacement of the endogenous TCR with the transgenic TCR (tgTCR) resulted in T cells with improved tgTCR expression levels and in 95% of edited T cells carrying exclusively the desired pairs of the tgTCR alpha and beta chains. This therapeutic TCR profile is expected to yield improved T cell product homogeneity, as researchers showed that Intellia’s T cell editing approach results in superior function of the engineered T cells toward WT1-positive targets in vitro. This therapeutic TCR profile is also expected to result in lower reactivity against unwanted targets on normal tissues that could lead to toxicities, including graft-versus-host disease (GvHD).

Researchers identified that the selected lead WT1 TCR exhibits high avidity (in the nM range) to its target epitope and shows tight epitope specificity. Being a natural TCR isolated from a healthy donor, it may have a lower cross-reactivity risk than many affinity-matured TCRs. Cells engineered with Intellia's lead WT1 TCR also demonstrated no detectable cytotoxicity toward bone marrow CD34+ cells, which express WT1 at low levels. This is an advantage over current CAR-T cell approaches targeting CD33 or CD123 in AML, which have been shown to induce severe bone marrow toxicity.

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