CAR-Treg transplantation (ENTX#SOT)

CAR-Treg transplantation program with the University of British Columbia

In October 2016, TxCell entered into 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.

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 are primarily conducted in the UBC laboratories and led by Professor Megan Levings.

In March 2016, her team published the first preclinical proof of concept with human HLA-A2-specific CAR-Treg cells in a preclinical transplantation model(1).

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.

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.

(1) MacDonald KG, Hoeppli RE, Huang Q, Gillies J, Luciani DS, Orban PC, Broady R, Levings MK. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J Clin Invest. 2016, 126(4):1413-1424

About the UBC CAR-Treg proof-of-concept

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.

About Organ Transplantation

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.

CAR-Treg lupus (ENTX#LN)

CAR-Treg Lupus Nephritis program in collaboration with Ospedale San Raffaele

In April 2016, TxCell entered into a strategic R&D collaboration with Ospedale San Raffaele (OSR), one of the most prestigious research institutions in Europe in the field of cell and gene therapy.

This collaboration includes a development arm focused on Lupus Nephritis, as well as a research program dedicated to CAR-Treg biology.

The development part of the collaboration focuses on the non-clinical development of Chimeric-Antigen-Receptor engineered regulatory T (CAR-Treg) cells for the treatment of Lupus Nephritis.

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, TxCell and OSR are conducting the non-clinical pharmacology and toxicology studies with CAR-Treg cells to prepare for a first-in-man study in Lupus Nephritis patients.

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

About Lupus Nephritis

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.

CAR-Treg dermatology (ENTX#BP)

CAR-Treg bullous pemphigoid program with the Lübeck Institute of Experimental Dermatology

In June 2016, TxCell entered into a strategic R&D collaboration agreement with the Lübeck Institute of Experimental Dermatology (LIED), a leading institution in the field of translational research on skin blistering diseases, part of the University of Lübeck in Germany.

This specific collaboration agreement covers the development of a CAR-Treg-based cellular immunotherapy for bullous pemphigoid, a rare, potentially fatal autoimmune disease characterized by tense inflammatory skin blisters and in some patients, erosions on mucous membranes.

TxCell scientists have already identified a relevant antigenic target for the development of a CAR-Treg product in bullous pemphigoid patients. The CAR construct is designed to ensure the activation of CAR-Treg cells specifically in the inflammatory skin lesions.

TxCell and LIED are conducting non-clinical pharmacology studies with CAR-Treg cells to prepare for a first in-man study in bullous pemphigoid patients.

About bullous pemphigoid

Bullous pemphigoid is a rare potentially fatal autoimmune skin condition that is characterized by large, fluid-filled blisters on the surface of the skin, called bullae.

Bullous pemphigoid occurs when the patient’s immune system attacks a thin layer of tissue below the outer layer of skin. The blisters usually develop on the abdomen, legs and arms and are accompanied by severe itching. Occasionally, the inner lining tissue of the mouth, nasal passages, or genitalia can be involved.

Bullous pemphigoid is most common in people aged 60 and older, with an estimated prevalence of 1/40,000.

If untreated, it will persist for years, with periods of spontaneous remissions and exacerbations. Current treatment is based on long-term use of corticosteroids such as prednisone.

Bullous pemphigoid can be life-threatening, especially for elderly people who are already in poor health.


Ovasave®, TxCell lead drug candidate from the ASTrIA platform, is a personalized T cellular immunotherapy product, based on the properties of autologous ovalbumin-specific regulatory T lymphocytes.

In 2016, TxCell identified a new isolation method for its non-engineered Treg cells (ASTrIA). This innovative procedure should enable a reduction of approximately 50% of both the production costs and the overall manufacturing leadtime, as well as a reduction of the risk of non-compliant manufacturing for future clinical trials and a potential commercial launch.

Combining these encouraging preliminary results and TxCell’s strict cost control policy, TxCell has decided to finalize and GMP-prove this new manufacturing process prior to the initiation of new clinical trials from the ASTrIA platform. Resulting from this decision, the clinical development of Ovasave® in refractory Crohn’s disease will not restart immediately.

CATS1 Phase I/IIa clinical study

The first-in-man phase I/IIa study, CATS1, was an open label, 12 weeks multicenter clinical trial, assessing the tolerability and exploring the efficacy of escalating and multiple doses of Ovasave® in patients with active moderate-to-severe refractory Crohn’s disease. Several eligible patients in CATS1 also received additional injections at the best responding dose.

CATS1 study has been completed on Q3 2011 and final results have been presented at major international medical conferences, published in Gastroenterology and reviewed in Nature.

Key findings

  • Ovasave® is well tolerated.
  • The positive effect of Ovasave® was particularly relevant in the best dose group with 75% of patients responding and 38% remitting five weeks after treatment.

About Crohn's disease

Crohn’s Disease is an inflammatory bowel disease that can affect the gastrointestinal tract from mouth to anus as well as present some extra-intestinal manifestations. Generally begins during adolescence and often affects young adults.

The cause of Crohn’s Disease is still unknown even though an interaction between a genetic predisposition and environmental factors is believed to be in the origin of the pathology. The incidence is about 6 to 15 cases per 100.000 and the prevalence of 50 to 200 cases per 100.000.

It is a chronic relapsing and remitting disease manifested mainly by abdominal pain, diarrhea and weight loss, together with systemic symptoms.

Patient’s quality of life may be significantly impaired with Crohn’s Disease.

There is currently no curative therapy and treatments aim at reducing the inflammation and manage the symptoms.

Medications used include immuno-suppressors and biologics (anti-TNF), which frequently show limited efficacy, tolerability issues and development of resistance.

It is estimated that about 160.000 patients live with severe Crohn’s Disease in Europe and the United States and about half of them have primary, secondary or tolerance failure to existing treatments.

There is a high unmet medical need for new treatment options to treat patients with Crohn’s disease.


Col-Treg is TxCell second product candidate in development.

Col-Treg is being developed to treat the rare disease Autoimmune Uveitis.

Col-Treg has Orphan Drug Designation in Europe and is classified as an Advanced Therapy Medicinal Product (ATMP) by the European Medicines Agency (EMA).

TxCell has already shown efficacy for Col-Treg in models of autoimmune diseases and toxicology studies on Col-Treg have shown the absence of tumourigenicity and confirmed the limited life span of the cells in vitro and in vivo.

The next step in this program will be a first clinical study.

Presentation of activity and tolerance data for Col-Treg

Poster presentation at the 2015 ARVO Annual Meeting on May 3-7 2015 in Denver, Colorado, USA

About Autoimmune Uveitis

Uveitis is an inflammatory condition of the eye affecting mainly the uvea, or middle layer of the eye that can lead to permanent vision loss. It is one of the leading causes of blindness in the developed world.

Uveitis is classified as a rare disease with a total incidence of 35-50/100,000.

Autoimmune Uveitis includes both non-infectious uveitis and idiopathic uveitis.

Other autoimmune disorders may be associated with the development of Autoimmune Uveitis, though the exact cause is often unknown.

The symptoms and characteristics of Autoimmune Uveitis include: eye redness, eye pain, light sensitivity, blurred vision and a decreased vision.

In all cases, the jelly-like material in the center of the eye (vitreous) can also become inflamed and infiltrated with inflammatory cells.

There is currently no curative therapy and available treatments aim at reducing the inflammation and manage the symptoms. The current first-line treatment consists of corticosteroids, often used with antimetabolites and alkylating agents. However, there are currently no approved options for the patients that become refractory to steroid compounds.

Autoimmune Uveitis is a serious rare disease and new therapeutic options are urgently needed.