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 a gene-edited allogeneic CAR T-cell product candidate, developed for treatment of CD19-expressing hematological malignancies. UCART19 is initially being developed in Acute Lymphoblastic Leukemia (ALL). The Cellectis approach with UCART19, developed in partnership with Servier and Allogene, is based on the preliminary positive results from clinical trials using autologous products based on the CAR technology. This new approach of using an allogeneic, frozen, “off-the-shelf” T-cell based medicinal product has the potential to overcome limitations experienced with autologous therapies, such as cost and availability.

In 2015, the first medical treatment of two young patients with refractory relapsed ALL occurred with gene-edited, off-the-shelf T-cells. Following this treatment, both of these patients then received a bone marrow transplant and are currently in remission. This first-in-human application of TALEN® engineered T-cell product represents a landmark in the use of gene engineering technology and provides encouraging data for a ready-made T-cell strategy that is currently being tested in clinical trials. Following an unsolicited request from Professor Waseem Qasim, Great Ormond Street Hospital (GOSH) treated both patients under a special license from the Medicines & Healthcare products Regulatory Agency (MHRA) with Cellectis’ TALEN® gene-edited allogeneic UCART19 product candidate.

On November 18, 2015, we signed an amendment to our collaboration agreement with Servier. Notably, Servier exercised its option to acquire worldwide rights to further develop and commercialize UCART19, which is now exclusively licensed to Allogene in the U.S., while Servier retains exclusive rights for all other countries.

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 the Phase I 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 mAb.

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

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 80% of patients with Acute Myeloid Leukemia (AML).

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 21,450 new cases expected for 2019, with 10,920 estimated deaths.

In February 2017, Cellectis received an Investigational New Drug (IND) approval from the U.S. Food and Drug Administration (FDA) to conduct Phase I clinical trials with UCART123 in patients with AML. 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 I, 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 I clinical trial in AML. The amendment increased the current tested dose levels, shortened the treatment interval between patients and added MD Anderson Cancer Center as a new clinical site for the study.

The clinical trial for AML is coordinated by principal investigator Prof. Gail J. Roboz, MD, Professor of Medicine at Weill Cornell Medicine and Director of the Clinical and Translational Leukemia Programs at Weill Cornell Medicine and NewYork-Presbyterian Hospital. Additional clinical sites include the MD Anderson Cancer Center in Houston, Texas, with Dr. Naveen Pemmaraju, MD, Assistant Professor, as principal investigator; the H. Lee Moffitt Cancer Center and Research Institute, in Tampa, Florida, with principal investigator Dr. David Sallman, MD, Assistant Member in the Malignant Hematology Department; and the Dana-Farber Cancer Institute in Boston Massachusetts, with principal investigator Dr. Daniel DeAngelo, Chief of the Division of Leukemia at Dana-Farber and Associate Professor of Medicine at Harvard Medical School.

Learn more about the ongoing clinical trial on 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 2019 (including both children and adults) are about 5,930 new cases and about 1,500 deaths. 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 I 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 I, 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 also designed for the treatment of B-Cell Non-Hodgkin Lymphoma (NHL). As mentioned above, Like CD19, CD22 is a cell surface antigen expressed from the pre-B-cell stage of development through mature B-cells. CD22 expression occurs on the vast majority of Non-Hodgkin Lymphomas.

NHL is a heterogeneous disease resulting from the malignant transformation of lymphocytes with distinctive morphologic, immunophenotypic, genetic, and clinical features. Non-Hodgkin Lymphoma is more common than the other general type of lymphoma — Hodgkin lymphoma. The past several decades have seen a steady increase in incidence rates of NHL, with overall rates in the United States nearly doubling over the period 1975 to 2008. In 2019, there are 74,200 estimated new cases with 19,970 estimated deaths. While there are many different subtypes of Non-Hodgkin Lymphoma that exist, the most common include diffuse large B-cell lymphoma and follicular lymphoma.

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, Assistant Professor, 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.

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