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 trials at www.clinicaltrials.gov.

UCART123 UCART22 UCARTCS1 UCART19 ALLO-501 ALLO-715

What is UCART123?

Our 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).

Cellectis obtained a new IND number from the FDA in July 2019 for a new UCART123 construct with an optimized production process. This new IND replaces our previous IND on UCART123.

UCART123 clinical study

The UCART123 clinical trial in AML, AMELI-01, is a Phase 1, dose escalation study to evaluate the safety, expansion, persistence and clinical activity of  a new UCART123 construct and an optimized production process in patients with relapsed/refractory AML. The first patient dosing in AMELI-01 happened in January 2020 at MD Anderson Cancer Center.

This clinical trial is led by Gail J. Roboz, M.D., Professor of Medicine at Weill Cornell Medicine and New York-Presbyterian (New York, USA), in collaboration with Naveen Pemmaraju, M.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center (Texas, USA), David Sallman, M.D., Assistant Member in the Malignant Hematology Department at H. Lee Moffitt Cancer Center (Florida, USA), and Daniel DeAngelo, M.D., Ph.D., Institute Physician and Director of Clinical and Translational Research of Adult Leukemia at Dana Farber Cancer Institute (Massachusetts, USA).

What is UCART22?

UCART22 is one of Cellectis’ wholly owned, allogeneic, off-the-shelf gene-edited T-cell product candidates designed for the treatment of relapsed and refractory B-cell acute lymphoblastic leukemia (R/R 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.

UCART22 clinical study

The Food and Drug Administration approved the Company’s Investigational New Drug application to initiate a Phase 1 clinical trial for UCART22, one of Cellectis’ wholly owned TALEN® gene-edited product candidate, for the treatment of B-ALL in adult patients.

The UCART22 clinical trial, BALLI-01, is a Phase 1, dose-escalation study to evaluate the safety, expansion, persistence and clinical activity of UCART22, a product candidate composed of engineered T-cells expressing anti-CD22 chimeric antigen receptors, in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).

The clinical trial is led by Dr. Nitin Jain, MD, Associate Professor, Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center (Houston, TX) in collaboration with Dr. Richard Larson, MD, Director of the Hematologic Malignancies Clinical Research Program at the University of Chicago Medicine (Chicago, IL) and with Dr. Gail Roboz, MD, Director, Clinical and Translational Leukemia Programs, Professor of Medicine, Weill Cornell Medical College The New York Presbyterian Hospital (New York, NY).

What is UCARTCS1?

UCARTCS1 is an allogeneic, off-the-shelf, gene-edited T-cell product candidate designed for the treatment of CS1/SLAMF7-expressing hematologic malignancies. UCARTCS1 is being investigated for safety, expansion, persistence and clinical activity of UCARTCS1 cells in refractory/relapsed multiple myeloma (R/R MM) patients.

MELANI-01 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 MELANI-01, a Phase 1 clinical trial for UCARTCS1, Cellectis' wholly controlled TALEN® gene-edited product candidate, for the treatment of patients with refractory/relapsed multiple myeloma (R/R MM). The trial officially commenced dosing patients under the supervision of Dr. Krina Patel, Principal Investigator, Study Coordinating Investigator, Assistant Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine at MD Anderson Cancer Center in Houston, Texas. The trial is also being conducted at Hackensack Meridian under the supervision of Dr. David Siegel, Director of the Multiple Myeloma Institute at John Theuer Cancer Center at Hackensack University Medical Center in Hackensack, New Jersey.

Another site is planned to open at Weill Cornell Medicine in New York under the leadership of Dr. Adriana Rossi, Associate Clinical Director, Myeloma Center and Assistant Professor of Medicine, Division of Hematology and Medical Oncology.

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 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. The Phase 1 UNIVERSAL study has started in relapsed/refractory multiple myeloma (MM) and is sponsored by Allogene.