TxCell SA, a biotechnology company developing innovative, personalized cellular immunotherapies using regulatory T cells (Treg) to treat severe chronic inflammatory and autoimmune diseases, announced the signature of a strategic R&D collaboration agreement with the University of British Columbia (UBC) in Vancouver, Canada, a leading global center for multidisciplinary research and teaching.

“As stated in our recent strategic update, TxCell continues to intensify its efforts on its ENTrIA platform of engineered regulatory T cells. TxCell has launched a third CAR-Treg collaboration in order to strengthen its recently initiated transplantation program,” said Stéphane Boissel, chief executive officer of TxCell. “Thanks to TxCell’s unparalleled expertise in the Treg space, we have secured access to the most advanced CAR-Treg programs worldwide. We expect this to help us achieve our goal of launching a first-in-man clinical study with a first CAR-Treg in 2018.”

This collaboration agreement covers the development of a CAR-Treg-based cellular immunotherapy for the prevention of graft rejection in the context of Solid Organ Transplantation (SOT). Activities relating to this program will be primarily conducted in the UBC laboratories. The activities will be led by Professor Megan Levings, who earlier this year established a first preclinical proof of concept with human HLA-A2-specific CAR-Treg cells in a preclinical transplantation model. UBC will conduct non-clinical pharmacology studies with CAR-Treg cells with the aim of initiating a first-in-man study in transplantation patients as soon as possible. “The recent in vivo proof of concept published by UBC in a leading international scientific journal is a critical milestone in the pioneering field of CAR-Treg cells,” said Arnaud Foussat, senior vice president, corporate development and head of external collaborations & alliance management of TxCell. “In contrast to existing approaches based on polyclonal Tregs already tested in clinical trials, we have chosen to bring antigen specificity through a CAR, with the aim of increasing the potential to address the vast unmet medical need in transplantation. We are honoured that Prof. Levings has chosen TxCell as its partner for this program and we are looking forward to our collaboration towards a common goal of initiating a first-in-man study as rapidly as possible.”

“TxCell has unique experience in the development of Treg-based cellular immunotherapies and we are excited to collaborate to develop CAR-Treg therapy for unmet medical needs in transplantation,” said Dr. Megan Levings, Professor, Department of Surgery, UBC and head, Childhood Diseases Research Theme, BC Children's Hospital. “The collaboration will allow us to assess the potential of CAR-Treg cells in preclinical models of solid organ transplantation.”

The UBC team demonstrated that, in a preclinical xenogeneic Graft-vs-Host Disease (GvHD) model, human CAR engineered Treg cells that are specific for the molecule HLA-A2 were more effective than polyclonal Treg cells in reducing GvHD-related inflammation. The model used by Dr. Levings’ team is based on xenogeneic GvHD induced in immunodeficient mice through the injection of human HLA A2+ white blood cells. These human white blood cells (graft) attack the immunodeficient mice (host), resulting in an inflammatory reaction (Graft-vs-Host Disease, GvHD). The CAR used in this experiment was designed to specifically recognize the HLA-A2 molecule found solely on graft cells. These data will constitute the basis for the first product development under the new TxCell/UBC collaboration.

Whilst the UBC team is focused on product development activities, it will in parallel perform research activities in the CAR-Treg field with the aim of optimizing and broadening the new product platform for transplantation.

TxCell has an exclusive option on programs and products developed under this agreement. Financial terms of the collaboration have not been disclosed.

Solid Organ Transplantation (SOT) consists in moving an organ (graft) from one body (donor) to another body (recipient or host), to replace the recipient's damaged or absent organ. More than 30,000 organ transplants were performed in the US in 2015, and more than 31,000 in Europe in 2013. Transplant rejection is one of the key challenges of transplantation. In order to avoid such rejection, the most appropriate donor-recipient match is sought and immunosuppressant drugs can be used. In 2014, the global market of immunosuppressant drugs used in transplantation was estimated to reach $5.1 billion. In the US alone, the cost of long term oral maintenance immunosuppression and other prescription drugs represents between $10,000 and $14,000 per patient per year on average, and can exceed $2,500 per month for certain patients. Novel strategies aiming at inducing or restoring immune tolerance to a graft are expected to be less toxic and more efficient on the long-term than classical pharmacological immunosuppressive approaches.