Universal Chimeric Antigen Receptors

UCART (Universal Chimeric Antigen Receptor T-cells) are “off-the-shelf” allogeneic products, whose production can be industrialized and thereby standardized with consistent pharmaceutical release criteria, over time and from batch to batch.

Universal Chimeric Antingen Receptor T-cells (UCARTs) represent a paradigm shift in terms of ease of use, availability and the drug pricing challenge.

Our lead immuno-oncology product candidates, which we refer to as UCARTs, are all allogeneic CAR T-cells engineered to be used for treating the largest number of patients with a particular cancer type. Each UCART product candidate targets a selected tumor antigen and bears specific engineered attributes, such as compatibility with specific medical regimens that cancer patients may undergo. UCART is our first therapeutic product line that we are developing with our gene editing platform to address unmet medical needs in oncology.

UCART19 is an allogeneic CAR T-cell product candidate developed for treatment of CD19-expressing hematological malignancies, gene edited with TALEN®. UCART19 is initially being developed in acute lymphoblastic leukemia (ALL). Cellectis’ approach with UCART19 is based on the preliminary positive results from clinical trials using autologous products based on the CAR technology, and has the potential to overcome the limitation of the current autologous approach by providing an allogeneic, frozen, “off-the-shelf” T cell based medicinal product.

In a medical first, two young patients were treated with gene edited off-the-shelf T-cells. The two infants each had leukemia and had undergone previous treatments that failed, according to a description of their cases published in January 2017 in Science Translational Medicine. This first-in-human application of our TALEN® engineered T-cell product candidate represents a landmark in the use of new gene engineering technology and provides encouraging data for a ready-made T-cell strategy that is currently tested in clinical investigations. GOSH has treated in 2015 these young patients under a special license from the Medicines & Healthcare products Regulatory Agency (MHRA) with Cellectis’ TALEN® gene edited allogeneic UCART19 product candidate because no other therapies were available for refractory relapsed acute lymphoblastic leukemia (ALL) following mismatched allogeneic stem cell transplantation. In response to an unsolicited request from Professor Waseem Qasim, Consultant Immunologist at GOSH and Professor of Cell and Gene Therapy at University College London (UCL) Institute of Child Health, Cellectis gave its approval for the use of its UCART19 product candidate and technologies under GOSH’s “Specials” license and responsibility, for the particular clinical needs of these patients.

On November 18, 2015, we signed with Servier an amendment to our collaboration agreement. Notably, Servier exercised its option to acquire exclusive worldwide rights to further develop and commercialize UCART19.

Phase I clinical trials started in adult and pediatric patients in Europe in June 2016 and in the U.S. in 2017.

Preliminary results from two phase 1 studies of UCART19 were presented in December 2017 at the 59th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta First-in-human data demonstrated the safety and tolerability of UCART19, resulting in an 83% complete remission rate across the adult and pediatric patient population

Our first wholly-controlled product candidate, UCART123 is a gene edited T-cell investigational drug that targets CD123, an antigen expressed at the surface of leukemic cells in AML, as well as on leukemic and other tumoral cells in BPDCN. Cellectis received in February 2017 an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) to conduct Phase 1 clinical trials with UCART123 in patients with acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN). This marks the first allogeneic, “off-the-shelf” gene-edited CAR T-cell product candidate that the FDA has approved for clinical trials.

The UCART123 program was subject to a public hearing by the National Institutes of Health's Recombinant DNA Advisory Committee (RAC) in December 2016, where it received the unanimous approval of the RAC committee members.

AML is a devastating clonal hematopoietic stem cell neoplasm that is characterized by uncontrolled proliferation and accumulation of leukemic blasts in bone marrow, peripheral blood and, occasionally, in other tissues. These cells disrupt normal hematopoiesis and rapidly cause bone marrow failure and death. In the U.S. alone, there are an estimated 19,950 new AML cases per year, with 10,430 estimated deaths per year.

The clinical research at Weill Cornell is led by principal investigator Dr. Gail J. Roboz, Professor of Medicine at Weill Cornell Medicine and Director of the Clinical and Translational Leukemia Programs at Weill Cornell Medicine and NewYork-Presbyterian.

BPDCN is a very rare and aggressive hematological malignancy that is derived from plasmacytoid dendritic cell precursors. BPDCN is a disease of bone marrow and blood cells but also often affects skin and lymph nodes.

The UCART123 clinical program at MD Anderson is led by Dr Naveen Pemmaraju, MD, Associate Professor, Dr Marina Konopleva, Professor, and Professor Hagop Kantarjian, MD, Department Chair, Department of Leukemia, Division of Cancer Medicine.

Learn more about the ongoing clinical trials at www.clinicaltrials.gov

 

UCART22 is an allogeneic, off-the-shelf gene-edited T-cell product candidate designed for the treatment of B-ALL. Like CD19, CD22 is a cell surface antigen expressed from the pre B-cell stage of development through mature B-cells and CD22 expression occurs in more than 90 percent of patients with B-ALL.

Acute lymphoblastic leukemia (ALL) is a rapidly progressing form of leukemia that is characterized by the presence of a large number of immature white blood cells in the blood and bone marrow. In 2016, an estimated 6,590 new cases were diagnosed in the U.S., with over 1,400 deaths due to ALL. Approximately 85 percent of ALL cases involve precursor B-cells (B-ALL).

Cellectis has submitted in May 2018 an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) requesting approval to initiate a Phase 1 clinical trial for UCART22, Cellectis’ second wholly controlled TALEN® gene-edited product candidate, for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) in adult patients.

Pending regulatory clearance, Cellectis plans to initiate a Phase I clinical trial in the third quarter of 2018. The clinical research will be led by Dr. Nitin Jain, Assistant Professor, and Prof. Hagop Kantarjian, Chairman in the Department of Leukemia and University Chair in Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston.

UCARTCS1 is an allogeneic gene-edited T-cell product candidate designed for the treatment of CS1-expressing hematologic malignancies. UCARTCS1 is being developed in multiple myeloma (MM). We expect to manufacture UCARTCS1 according to GMP in 2018, for purposes of conducting a clinical trial at MD Anderson Cancer Center. Translational activities for UCARTCS1 in MM are performed in collaboration with the MD Anderson Cancer Center.

UCART38 is an allogeneic gene-edited T-cell product candidate designed for the treatment of CD38-expressing hematologic malignancies. UCART38 is being developed in Multiple Myeloma, T-cell ALL, Non-Hodgkin lymphoma and Mantle cell lymphoma. UCART38 is at an early preclinical stage. Preclinical and translational activities on UCART38 in T-ALL are to be performed in collaboration with the MD Anderson Cancer Center.