Cellectis Presents Initial Preclinical Data on Two Novel Gene Therapies for Patients with RAG1 Severe Combined Immunodeficiency (SCID) and Hyper IgE syndrome at ESGCT 2021

Published on October 19, 2021 in New York, NY

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October 19, 2021 – New York - Cellectis S.A. (NASDAQ: CLLS – EURONEXT GROWTH: ALCLS) (the “Company”), a gene-editing company with clinical-stage immuno-oncology programs using allogeneic chimeric antigen receptor (CAR)-T cells and gene therapy programs for genetic diseases, in collaboration with Professor Toni Cathomen, scientific director at the Center for Chronic Immunodeficiency Medical Center at the University of Freiburg, Germany, will present two oral presentations at the European Society of Gene and Cell Therapy (ESGCT) Congress to be held virtually from October 19-22, 2021.

Professor Cathomen’s team at University of Freiburg will be presenting encouraging pre-clinical data that supports further evaluation of Cellectis’ .HEAL platform, an innovative gene therapy platform that uses a genome editing approach based on TALEN® , for two product candidates targeting primary immunodeficiencies: RAG1 for Severe Combined Immunodeficiency (SCID) and STAT3 for Hyper IgE syndrome.

‘The data accepted for presentation at ESGCT reflects our ongoing commitment to finding new ways to treat and potentially provide a cure to patients that have failed to respond to standard therapies. Utilizing Cellectis’ TALEN® technology, which we believe to be the most precise, versatile, and effective gene editing tool currently available, we demonstrate our potential to precisely correct RAG1 and STAT3 deficient genes and restore functionalities of the gene. These new milestones bring us one step closer to our goal of unlocking the full potential of our gene editing platform and bringing new therapies to patients with unmet medical needs.’ said Philippe Duchateau, Ph.D, Chief Scientific Officer of Cellectis.

Last May, during Cellectis’ Innovation Days, the Company revealed its new .HEAL platform, a novel hematopoietic stem cell gene therapy that aims to address debilitating genetic diseases. .HEAL leverages the power of TALEN® gene editing technology to perform genome surgery, resulting in highly efficient and precise gene inactivation, insertion, and correction in hematopoietic stem cells (HSCs). Cellectis has announced ongoing programs targeting sickle cell disease, lysosomal storage disorders and primary immunodeficiencies.

Presentations details

Data presentation on preclinical development of a TALEN® based genome editing therapy for RAG1 deficiency

Newborns with RAG1 SCID have extremely low levels of B and T cells and a severe risk of recurrent, life-threatening infections. RAG1 is an essential enzyme specifically and temporarily expressed in the early development of T and B cells, making traditional gene therapy approaches to treat the disease challenging due to the need for tight and precise spatio-temporal expression control.

Previous attempts to treat the RAG1 deficiency via conventional gene therapy have produced unsatisfactory results.

These results highlight the need for tight spatio-temporal control of RAG1 expression as key for functional restoration and the use of a gene editing tool.

Using Cellectis’ TALEN® technology and .HEAL, Professor Cathomen engineered HSCs with a corrected copy of RAG1 that replaced the existing, mutated copy of RAG1. The precise replacement of the mutated gene enabled the corrected RAG1 gene to be expressed at its natural timing and stage of cell development.

30% of gene correction was achieved within the long-term HSC population.

The presentation titled ‘Preclinical development of a TALEN based genome editing therapy for RAG1 deficiency’ will be made on October 21 (9-11AM CET) by Manuel Rhiel, Ph.D University of Freiburg, and can be found on the ESGCT website.

Presentation Details:

Data presentation on a preclinical development of a TALEN® based genome editing in T-cells for the treatment of Hyper-IgE- Syndrome

Hyper IgE syndrome is a rare primary immunodeficiency disease that clinically manifests as skin inflammation and recurrent skin and lung infections. Mutations in the transcription factor STAT3 have been associated with Hyper IgE. Alternative splicing gives rise to two STAT3 isoforms, STAT3α and STAT3β that display distinct functions.

The α/β ratio needs to be tightly regulated, which represents a major challenge for traditional gene therapy approaches.

Cellectis has developed a strategy applicable in HSCs and T-cells to insert a corrected version of the STAT3 gene into the patient’s genome to restore its functionality.

In T-cells isolated from patients, 60% integration was achieved. More importantly, the α/β isoforms ratio was restored.

The presentation titled ‘Preclinical development of a TALEN based genome editing in T cells for the treatment of Hyper-IgE-Syndrome' will be made on October 20 (9-11AM CET) by Viviane Dettmer, Ph.D, University of Freiburg, and can be found on the ESGCT website.

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