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.

 

Learn more about the ongoing clinical trial at www.clinicaltrials.gov and https://www.clinicaltrialsregister.eu/.

What is UCART19?

UCART19 is an allogeneic CAR T-cell product candidate developed for the treatment of CD19-expressing hematological malignancies, which has been engineered using TALEN® gene editing technology. This product candidate was developed by Cellectis before entering into a license agreement with Servier, and is initially being developed in relapsed/refractory acute lymphoblastic leukemia (ALL). Cellectis’ approach with UCART19 was based on the preliminary positive results from clinical trials using autologous CAR T-cells, but bringing the potential to overcome the limitation of the current autologous approach by providing an allogeneic, frozen, off-the-shelf T-cell based medicinal product.

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, which is now being jointly developed by Servier and Allogene. Allogene has exclusive rights to UCART19 in the U.S. while Servier retains exclusive rights for all other countries

A medical first

In 2015, in a medical first, two young patients were treated with gene-edited off-the-shelf T-cells. The two infants had leukemia and did not respond to previous treatments, 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 was and still is 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. Great Ormond Street Hospital treated these young patients in 2015 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.

Encouraging data as a solid proof-of-concept for Cellectis’ leading allogeneic approach

Phase 1 clinical trials started in adult and pediatric patients in the U.K. in June 2016 and in the U.S. in 2017. Since then, several clinical sites opened in France, Belgium, Spain and Japan.

Preliminary results from two Phase 1 studies of UCART19 were presented in December 2018 at the 60th American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego. First-in-human data demonstrated the safety and tolerability of UCART19, resulting in an 82% complete remission rate across the adult and pediatric patient population who received a lymphodepletion regimen consisting of fludarabine, cyclophosphamide and an anti-CD52 monoclonal antibody.

What is UCART123?

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 acute myeloid leukemia (AML), and other pathologies.

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 AML and BPDCN.

UCART123 clinical studies

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.

In May 2018, the FDA approved an amendment to the protocol for the UCART123 Phase 1 clinical trial in AML. This amendment includes an increase of dose level 1, a dose limiting toxicities observation period decrease, a shortened interval between the first and the second patient for UCART123 infusion at each new dose level tested, and a potential second UCART123 infusion.

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 New York-Presbyterian, in the state of New York. The AML clinical study at MD Anderson is led by Dr. Naveen Pemmaraju, MD, Associate Professor, Department of Leukemia, Division of Cancer Medicine, at the University of MD Anderson Cancer Center in Houston, Texas. Two new clinical sites opened in late 2018, led by Dr. David Sallman, MD, Assistant Member in the Malignant Hematology Department of the H. Lee Moffitt Cancer Center and Research Institute, in Tampa, Florida, and by Dr. Daniel DeAngelo, MD, Institute Physician and Director of Clinical and Translational Research of Adult Leukemia at Dana-Farber Cancer Institute in Boston, Massachusetts. He is Associate Professor of Medicine at Harvard Medical School.

What is UCART22?

UCART22 is an allogeneic, off-the-shelf gene-edited T-cell product candidate designed for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) in relapsed and refractory setting. 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.

UCART22 clinical study

In June 2018, Cellectis announced that the Food and Drug Administration approved the Company’s Investigational New Drug application to initiate a Phase 1 clinical trial for UCART22, Cellectis’ second wholly controlled TALEN® gene-edited product candidate, for the treatment of 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-ALL.

UCART22 is the third allogeneic, off-the-shelf, gene-edited CAR T-cell product candidate approved by the FDA for clinical trials in the U.S. The research for UCART22 will be led by Dr. Nitin Jain, MD, Associate Professor, Department of Leukemia, Division of Cancer Medicine at the University of MD Anderson Cancer Center in Houston, Texas. The clinical study is also conducted at the University of Chicago Medicine, Illinois, under the supervision of Dr. Richard A. Larson, MD, Director of the Hematologic Malignancies Clinical Research Program, and at Weill Cornell Medicine and New York-Presbyterian, under the supervision of Prof. Gail J. Roboz, MD, Professor of Medicine and Director of the Clinical and Translational Leukemia Programs.

What is UCARTCS1?

UCARTCS1 is an allogeneic gene-edited T-cell product candidate designed for the treatment of CS1/SLAMF7-expressing hematologic malignancies. UCARTCS1 is being developed in multiple myeloma (MM).

UCARTCS1 clinical study

In January 2019, 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 UCARTCS1, Cellectis’ third wholly controlled TALEN® gene-edited product candidate, for the treatment of patients with refractory/relapsed multiple myeloma. The UCARTCS1 clinical trial is coordinated by Principal Investigator Dr. Krina Patel, MD, Assistant Professor of Medicine, Department of Lymphoma/Myeloma, Division of Cancer Medicine at MD Anderson Cancer Center in Houston, Texas. The trial is also conducted at John Theurer Cancer Center at Hackensack University Medical Center, New Jersey, under the supervision of Dr. David Siegel, MD, PhD, Director of the Multiple Myeloma Institute.

What is UCARTCLL1?

UCARTCLL1 is an allogeneic gene-edited T-cell product candidate designed for the treatment of CLL1-expressing hematologic malignancies, as acute myeloid leukemia (AML). UCART CLL1 is in development , specifically in preclinical and process development stages.

What is ALLO-501?

ALLO-501 is progressing under a joint clinical development collaboration between Servier and Allogene, and is exclusively licensed from Cellectis.

ALLO-501 features the same construct and the same editing process than UCART19 but is manufactured using a different process. Allogene has exclusive rights to ALLO-501 in the U.S. while Servier retains exclusive rights for all other countries.

ALLO-501 clinical study

The United States Food and Drug Administration (FDA) has granted investigational new drug (IND) for ALLO-501 in January 2019. The Phase 1 has started in relapsed/refractory non-Hodgkin lymphoma and is sponsored by Allogene.

The clinical study is conducted at Banner MD Anderson Cancer Center in Arizona, at the University of California, Los Angeles, at Colorado Blood Cancer Institute, in Denver, at the H. Lee Moffitt Cancer Center and Research Institute, in Tampa, Florida, and at MD Anderson Cancer Center in Houston, Texas.

What is ALLO-715?

ALLO-715 is an engineered allogeneic chimeric antigen receptor T (CAR T) cell therapy targeting BCMA, exclusively licensed to Allogene, for the treatment of patients with relapsed/refractory multiple myeloma (MM).

ALLO-715 clinical study

On June 4, 2019, Allogene announced FDA clearance of the IND for ALLO-715. Allogene plans to initiate the UNIVERSAL Study for ALLO-715 in relapsed/refractory MM in the second half of 2019.

ALLO-819 is an engineered allogeneic chimeric antigen receptor T (CAR T) cell therapy targeting FLT3, exclusively licensed to Allogene, for the treatment of patients with relapsed/refractory acute myeloid leukemia (AML) and is under preclinical development.