Positive Data From Type 1 Diabetes Study of TolerRx’s TRX4 Published in the New England Journal of Medicine

CAMBRIDGE, Mass., June 23 /PRNewswire/ — A study published in the June 23 issue of the New England Journal of Medicine demonstrates that in patients with type 1 diabetes, a six day course of therapy with TRX4 (ChAglyCD3) preserves the function of insulin-producing beta cells in the pancreas and reduces the amount of administered insulin needed to control blood glucose levels for at least 18 months.

The study was conducted by a team of clinicians and researchers from France, Belgium, Germany, and England and led by Dr. Lucienne Chatenoud, from the Hopital Necker in Paris, as the Principal Investigator and Dr. Bart Keymeulen, from the Academic Hospital at Brussels Free University — VUB, as the clinical coordinator. The trial was undertaken by the JDRF Center for Beta Cell Therapy in Europe, directed by Dr. Daniel Pipeleers (Brussels Free University — VUB). The study was supported by the Juvenile Diabetes Research Foundation and was performed in collaboration with Dr. Herman Waldmann and his laboratory at the University of Oxford. TolerRx, Inc. is developing TRX4 for the treatment of patients with autoimmune diseases, including type 1 diabetes and psoriasis.

“Maintaining or improving beta cell function is a major achievement in the treatment of type 1 diabetics,” stated Dr. Chatenoud. “The results suggest that TRX4 therapy results in greater endogenous insulin production and a corresponding reduction in administered insulin need. TRX4 therapy would be expected to result in better long-term metabolic control for these patients.”

“We are very encouraged by the results of this study and the implications it has for modifying the disease course in patients with type 1 diabetes,” said Douglas J. Ringler, V.M.D., President and CEO of TolerRx. “We look forward to working with our dedicated investigators and regulatory agencies so that TRX4 can be definitively established as the accepted inductive therapy for type 1 diabetes.”

Study Results

The multicenter study included 80 subjects recently diagnosed with type 1 diabetes. Subjects in the trial were randomly assigned to receive either TRX4 (ChAglyCD3) or placebo for only six consecutive days. During the 18 months following treatment, subjects were monitored for daily insulin needs and endogenous insulin production as assessed by measuring C-peptide release induced by an intravenous glucose infusion. At six, 12, and 18 months, beta cell function was more effectively maintained in TRX4-treated subjects than in placebo-treated subjects.

Daily insulin dose increased in the placebo group, but not in the TRX4 group. The effect of TRX4 was most pronounced in the patient subgroup with better (greater than the median) beta cell function at study start. In this subgroup, mean insulin dose at 18 months was 0.22 IU/kg/day versus 0.61 IU/kg/day in the corresponding placebo subgroup (p <0.001). Seventy-five percent of subjects in the TRX4 subgroup received minimal doses of insulin (less than or equal to 0.25 IU/kg/day) compared to zero percent of subjects in the corresponding placebo subgroup. TRX4 administration was associated with transient symptoms of flu-like syndrome and transient EBV reactivation.

Study Design

This Phase II study was conducted at five research sites and was a double- blind, placebo-controlled randomized trial with 40 subjects receiving TRX4 and 40 receiving placebo. Subjects were given at least three insulin injections per day and monitored their blood glucose with the goal of maintaining glucose levels between 80-140mg/dl and HbA1c levels lower than seven percent.

About Type 1 Diabetes

Diabetes (medically known as diabetes mellitus) is the name given to disorders in which the body has difficulty regulating its blood glucose, or blood sugar, levels. There are two major types of diabetes: type 1 and type 2. Type 1, also called juvenile diabetes or insulin-dependent diabetes, is a disorder of the body’s immune system. In type 1 diabetes, the pancreas produces little or no insulin as a result of the immune system attacking and destroying the insulin-producing beta cells in the pancreas. Therefore, type 1 diabetes patients require frequent administration of insulin therapy each day to control their blood sugar levels.

In the United States, approximately 1.3 million people have type 1 diabetes, and each year approximately 30,000 new patients are diagnosed with the disease, including 13,000 children.

About TRX4

TRX4 (ChAglyCD3) is a humanized monoclonal antibody that binds to a receptor found on all T cells called CD3, which is involved in normal T cell signaling. TRX4 is designed to block the function of autoreactive T-effector cells that attack the body and cause autoimmune disease. Because T-effector cells and T-regulatory cells utilize different signaling pathways for activation, TRX4 is expected to suppress autoreactive T cells while promoting T-regulatory cell activity resulting in a state of immunological tolerance. TolerRx is currently discussing with the FDA clinical trial designs to determine the safest and lowest effective dose of TRX4 in type 1 diabetes.

About TolerRx, Inc.

TolerRx, Inc. is a biopharmaceutical company focused on the discovery, development, and commercialization of novel therapies to treat patients with immune-mediated diseases. TolerRx’s therapies induce and maintain immunological tolerance, the process by which the immune system identifies and avoids attacking the body’s own tissues and proteins. In addition to TRX4 in clinical development in type 1 diabetes and psoriasis, TolerRx’s TRX1 monoclonal antibody is in Phase Ib clinical development in collaboration with Genentech, Inc. TolerRx also has research and discovery programs generating new products to induce immunological tolerance for the treatment of autoimmune diseases. For further information, please visit http://www.tolerrx.com/.

    TolerRx, Inc. Contact:     European Contact:    Dr. Douglas J. Ringler     Dr. Lucienne Chatenoud    (617) 452-1300             Hopital Necker-Enfants Malades, Paris, France    dringler@tolerrx.com       chatenoud@necker.fr  

TolerRx, Inc.

CONTACT: Dr. Douglas J. Ringler of TolerRx, Inc., +1-617-452-1300,dringler@tolerrx.com; European Contact: Dr. Lucienne Chatenoud of HopitalNecker-Enfants Malades, chatenoud@necker.fr

Web site: http://www.tolerrx.com/