Intellia Therapeutics Presents New Preclinical Data Supporting Its CRISPR/Cas9-Engineered TCR-T Cell Treatment for Acute Myeloid Leukemia at the 62nd ASH Annual Meeting

  • Lead immuno-oncology development candidate NTLA-5001 shows high anti-tumor activity as promising cancer treatment in proof-of-concept mouse models of acute leukemias
  • Proprietary process enhances tumor control in preclinical models and enables efficient, scalable genome editing and T cell manufacturing for NTLA-5001
  • First-in-human trial will evaluate safety and activity of NTLA-5001 in AML patients

CAMBRIDGE, MA, USA I December 05, 2020 I Intellia Therapeutics, Inc. (NASDAQ:NTLA), is presenting new preclinical data in support of NTLA-5001, the company’s wholly owned Wilms’ Tumor 1 (WT1)-directed T cell receptor (TCR)-T cell therapy candidate for the treatment of acute myeloid leukemia (AML), at the 62nd American Society of Hematology (ASH) Annual Meeting, taking place virtually from December 5-8, 2020. NTLA-5001 capitalizes on how natural T cells recognize and respond to tumors. The target, WT1, is highly overexpressed in AML, a cancer of the blood and bone marrow that is often fatal despite existing treatments (NIH SEER Cancer Stat Facts: Leukemia – AML). The new preclinical data being presented today highlight the faster expansion and superior function of T cells manufactured by Intellia’s proprietary approach, compared to a standard genome editing process. Specifically, NTLA-5001’s lead TCR-T cells resulted in significantly higher anti-tumor activity in mouse models of acute leukemias than that observed in mice treated with cells engineered using the standard process.

“NTLA-5001 is the first potential CRISPR-based cancer treatment engineered using Intellia’s proprietary process. Based on our preclinical results, we believe our process will result in a pipeline of safer and more efficacious oncological products, with reduced manufacturing time and, importantly, reduced vein-to-vein time, compared to currently available approaches. Showing in vivo efficacy in acute leukemia mouse models, as presented today at ASH, is extremely encouraging and an important steppingstone to entering the clinic next year,” said Intellia President and Chief Executive Officer John Leonard, M.D. “In our first-in-human trial, we plan to establish the safety and activity that will enable us to move quickly to a pivotal investigation of NTLA-5001 for the treatment of AML, which is the most common type of acute leukemia in adults.”

NTLA-5001 is being developed using Intellia’s proprietary process to treat AML patients regardless of the genetic subtype of a patient’s leukemia. Intellia plans to submit an Investigational New Drug (IND) application or equivalent for NTLA-5001 in the first half of 2021, subject to the impact of the COVID-19 pandemic, with the first-in-human trial planned to evaluate safety and activity in patients with persistent or recurrent AML who have previously received first-line therapies. Additional efforts are underway to evaluate the potential use of NTLA-5001 to treat WT1-positive solid tumors.

Presentation Details

Title: “NTLA-5001, a T Cell Product Candidate with CRISPR-Based Targeted Insertion of a High-Avidity, Natural, WT1-Specific TCR, Shows Efficacy in In Vivo Models of AML and ALL”
Publication Number: 1435
Session Name: 703. Adoptive Immunotherapy: Poster I
Presenting Author: Birgit Schultes, Ph.D., vice president of Intellia’s Cell Therapy group

With Intellia’s proprietary T cell engineering process, CRISPR/Cas9 in combination with adeno-associated virus (AAV) is used to insert a WT1-directed TCR in locus, while eliminating the expression of the endogenous TCRs. Benefits of Intellia’s approach include the following:

  • Intellia’s proprietary T cell engineering process enables multiple, sequential gene edits and is a significant improvement over standard engineering processes commonly used to introduce proteins and nucleic acids into cells.
  • Sequential editing maintains high T cell viability and may result in safer T cell products because treated cells have minimal levels of translocations, similar to unedited cells, and do not cause graft-versus-host disease (GvHD).
  • The observed faster T cell expansion with favorable T cell memory phenotype could lead to a reduced vein-to-vein time and better T cell persistence in patients, respectively.

T cells engineered using Intellia’s proprietary process to express the lead TCR to the WT137-45 epitope are efficacious, durable and safe in vivo in gold-standard mouse models of AML and acute lymphocytic leukemia (ALL). In collaboration with Chiara Bonini’s team at IRCCS Ospedale San Raffaele (OSR), the AML mouse model was developed using patient-derived primary AML blasts. WT1-specific T cell administration inhibited tumor growth more significantly and durably in blood, bone marrow and spleen than T cells edited using an industry standard electroporation process. Researchers additionally used an aggressive ALL model in immunocompromised mice engineered to express T cell-supporting cytokines at levels comparable to those in patients post-conditioning regimen, or post-lymphodepletion. In the ALL model, WT1-specific T cells also bestowed significant tumor control.

The presentation can be found here, on the Scientific Publications & Presentations page of Intellia’s website.

About Intellia Therapeutics

Intellia Therapeutics is a leading genome editing company, focused on the development of proprietary, potentially curative therapeutics using the CRISPR/Cas9 system. Intellia believes the CRISPR/Cas9 technology has the potential to transform medicine by both producing therapeutics that permanently edit and/or correct disease-associated genes in the human body with a single treatment course, and creating enhanced engineered cells that can treat oncological and immunological diseases. Intellia’s combination of deep scientific, technical and clinical development experience, along with its leading intellectual property portfolio, puts it in a unique position to unlock broad therapeutic applications of the CRISPR/Cas9 technology and create new classes of therapeutic products. Learn more about Intellia Therapeutics and CRISPR/Cas9 at Follow us on Twitter @intelliatweets. 

SOURCE: Intellia Therapeutics

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