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 - Seite 2

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 WT1_37-45 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.