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 clinical trial in AML is a Phase 1, open label dose-escalation and dose expansion study to evaluate the safety, expansion, persistence and clinical activity of UCART123 cells administered in patients with relapsed/refractory AML, and patients with newly diagnosed high-risk AML.

In May 2018, the FDA approved an amendment to the protocol for the UCART123 Phase 1 clinical trial in AML. In addition, a new AML clinical center has been opened at MD Anderson Cancer Center in Houston, Texas, aiming at increasing the patient enrollment pace.

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 were an estimated 21,000 new AML cases in 2017, with 10,000 estimated deaths per year.

The clinical research for AML is coordinated by principal investigator Prof. Gail J. Roboz, MD, at Weill Cornell, Professor of Medicine at Weill Cornell Medicine and Director of the Clinical and Translational Leukemia Programs at Weill Cornell Medicine and NewYork-Presbyterian. The AML clinical study at MD Anderson is led by Prof. Hagop Kantarjian, MD, Department Chair, Department of Leukemia, Division of Cancer Medicine, and Dr. Naveen Pemmaraju, MD, Assistant Professor, being Principal Investigator.

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. Cellectis’ UCART123 was administered to the first patient with blastic plasmacytoid dendritic cell neoplasm (BPDCN) in a Phase 1 clinical trial at MD Anderson Cancer Center in August 2017.

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. CD22 expression occurs in more than 90% of patients with B-ALL.

Acute lymphoblastic leukemia (ALL) is a heterogeneous hematologic disease characterized by the proliferation of immature lymphoid cells in the bone marrow, peripheral blood, and other organs. It can start either with early B-cells or T-cells at different stages of maturity. The American Cancer Society’s estimates for ALL in the United States for 2018 (including both children and adults) are about 5,960 new cases of ALL and about 1,470 deaths from ALL. Approximately 85% of ALL cases involve precursor B-cells (B-ALL).

In June 2018, Cellectis announced that the U.S. Food and Drug Administration (FDA) approved the Company’s Investigational New Drug (IND) application 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.

The UCART22 clinical trial is a Phase 1, open label dose-escalation and dose-expansion study to evaluate the safety, expansion, persistence and clinical activity of UCART22 (allogeneic engineered T-cells expressing anti-CD22 chimeric antigen receptor) in patients with relapsed or refractory CD22+ B-cell acute lymphoblastic leukemia (B-ALL).

UCART22 is the 3rd allogeneic, off-the-shelf, gene-edited CAR T-cell product candidate approved by the FDA for clinical trials in the U.S. Cellectis intends to begin the UCART22 Phase 1 study in the second half of 2018. The research for UCART22 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.