TxCell SA, a biotechnology company developing innovative, personalized cellular immunotherapies using regulatory T cells (Treg) to treat severe chronic inflammatory and autoimmune diseases, and Ospedale San Raffaele (OSR), one of the most prestigious research institutions in Europe in the field of cell and gene therapy, have entered into a strategic R&D collaboration. The collaboration will include a development arm focused on Lupus Nephritis, as well as a research programme dedicated to CAR-Treg biology.

The development part of the collaboration will focus on the non-clinical development of Chimeric-Antigen-Receptor engineered regulatory T (CAR-Treg) cells for the treatment of Lupus Nephritis. Lupus Nephritis is one of the most serious complications of Lupus, a chronic autoimmune disease affecting over 5 million people worldwide. TxCell scientists identified a first relevant antigenic target for its CAR-Treg cellular therapy product. They successfully created a CAR-Treg product candidate by engineering FoxP3+ Treg cells with a CAR. This CAR integrates the binding domain of a pathogenic antibody from patients suffering from Lupus Nephritis.

As per the terms of the agreement announced, TxCell and OSR will conduct the non-clinical pharmacology and toxicology studies with CAR-Treg cells to prepare for a first-in-man study in Lupus Nephritis patients.

“The R&D partnership between TxCell and the world-leading Ospedale San Raffaele is an important development for TxCell. We have already achieved very quick progress with ENTrIA, our new CAR-Treg platform. TxCell will use both the collaboration with OSR as well as guidance from our newly appointed Scientific Advisory Board to accelerate further development,” said Dr. Arnaud Foussat, CSO of TxCell. “TxCell looks forward to leveraging its unparalleled technology to contribute to treatments for Lupus Nephritis, one of the world's most devastating yet underserved diseases. In addition to our first programme in Lupus Nephritis, TxCell expects to start two additional CAR-Treg programs later this year on the back of additional in vitro and in vivo data.”

In parallel, the collaboration will also include a research arm, where OSR will perform research for TxCell on the design and biology of other chimeric antigen receptors for use in Treg cell products addressing other autoimmune indications.

Dr. Attilio Bondanza, Head of the Innovative Immunotherapies Unit at Ospedale San Raffaele, will lead the OSR team both in the development of CAR-Tregs in Lupus Nephritis and in the research program on CAR-Treg biology. Prof. Fabio Ciceri, Head of the Hematology and Bone Marrow Transplantation Unit and Deputy Director of the Division of Regenerative Medicine, Stem Cells and Gene Therapy of OSR, will also join the collaboration members. As a result of his pioneering experience in the field of clinical T-cell gene therapy, he will steer the collaboration towards a first-in-man study.

“We are very excited about this collaboration with TxCell, which certainly constitutes a major and unparalleled step forward towards the validation of the CAR technology outside the oncology field,” said Dr. Attilio Bondanza. “We enthusiastically accept the challenges of adapting the design of CARs to the distinctive biology of Tregs and we are really looking forward to developing robust protocols for the production of safe and effective cellular products that may benefit patients suffering from severe autoimmune diseases such as Lupus Nephritis.”

Financial terms of the collaboration have not been disclosed.

Lupus Nephritis is one of the most serious complications of Lupus (also called systemic lupus erythematosus, SLE). Lupus is a chronic autoimmune disease involving many systems and organs in the human body, including joints, kidneys, central nervous system, heart and the hematological system. The biologic basis of Lupus is a defect in the immune (defense) system. This leads to production of self (auto) antibodies, attacking the normal organs and causing irreversible damage. Lupus Nephritis occurs when systemic Lupus causes an inflammation in the kidney, due to the formation and deposit of immune complexes in the kidney. If this inflammation is not controlled, Lupus Nephritis can lead to kidney failure. According to the Lupus Foundation of America, at least 5 million people worldwide have Lupus, with more than 16,000 new cases diagnosed each year in the US alone. The majority of patients are women of childbearing age. It is estimated that up to 60% of Lupus patients will develop clinically relevant Nephritis at some time in the course of their illness.

ENTrIA (Engineered Treg for Inflammation and Autoimmunity) is the second TxCell proprietary cellular immunotherapy product platform and is composed of Chimeric Antigen Receptor engineered FoxP3+ Regulatory T cells (CAR-Treg). After their isolation from the blood of patients, FoxP3+ Treg cells are genetically modified by transduction with Chimeric Antigen Receptors (CAR). The CAR introduced into FoxP3+ Treg cells is designed to allow FoxP3+ Treg cell activation and immuno-modulation through in vivo recognition of a protein present in inflamed areas in patients suffering from autoimmune and chronic inflammatory diseases.