Single Short Course of Tolerx's Otelixizumab Provides Prolonged Preservation of Beta Cell Function

CAMBRIDGE, Mass., March 16 /PRNewswire/ -- Tolerx, Inc., today announced the publication in Diabetologia, the journal of the European Association for the Study of Diabetes, of the four-year follow-up clinical data from new onset type 1 diabetes (T1DM) patients (age 12-39) who received a single short course of therapy with otelixizumab (ChAglyCD3).  In this clinical study conducted by the Juvenile Diabetes Research Foundation (JDRF) Center for Beta Cell Therapy in Diabetes based in Brussels, patients treated with otelixizumab were characterized by the preservation of function of insulin-producing beta cells in the pancreas compared to patients treated with placebo for up to 4 years after treatment.  The data from this study are the first placebo-controlled demonstration of long term effects resulting from an innovative immunologic intervention in newly diagnosed T1DM cases.

The study results reported in Diabetologia were obtained through a collaboration between clinical and laboratory researchers in Belgium, France, Germany and the United Kingdom that was made possible by a grant from the JDRF (New York). The Belgian Diabetes Registry collected and analyzed blood samples and centralized data.

"The availability of four year efficacy and safety data with otelixizumab further advances our clinical development program in type 1 diabetes," said Dr. Douglas J. Ringler, President and Chief Executive Officer of Tolerx. "Tolerx is grateful to all the patients, caregivers, clinical trial investigators, and the JDRF for conducting and funding this study.  Tolerx is excited to be continuing the development of otelixizumab, and we look forward to very shortly initiating our second Phase 3 trial (DEFEND-2) in new onset autoimmune type 1 diabetes."    

Dr. Daniel Pipeleers, Director of the JDRF Center Brussels commented "Our data provide strong support to a novel disease modifying treatment for new-onset T1DM patients.  The data showed that immune modulation by otelixizumab dampen the autoimmune destruction process thereby preserving residual beta cells and their contribution to glycemic control."        

In this reported study, otelixizumab administration was associated with transient symptoms during dosing including flu-like syndrome and transient perturbation of Epstein Barr Virus (EBV).  During the 48 months of follow-up there were no EBV related symptoms, no higher incidence of infections, and no lymphoproliferative or other types of cancer observed.  Following the 18 month efficacy results of the present study, Tolerx has optimized the otelixizumab dosing regimen to minimize adverse events, with encouraging data on clinical effect.   This optimized dosing regimen is now being fully evaluated in a Phase 3 clinical study called DEFEND-1, which completed enrollment in January 2010, and will be confirmed in a second pivotal study, DEFEND-2.  DEFEND-2 is intended to begin in the first half of 2010.    

About the Study

The multicenter study included 80 patients with new onset diagnosed with type 1 diabetes. Patients in the study were randomly assigned to receive either otelixizumab (then called ChAglyCD3) or placebo for six consecutive days. During the 48 months following treatment, patients were monitored for daily insulin needs and endogenous insulin production as assessed by measuring C-peptide release induced by an intravenous glucose infusion. At 6, 12, 18, 24, 36 and 48 months, beta cell function was more effectively maintained in otelixizumab-treated subjects than in placebo-treated patients.  Data on the first 18 months have been published in N Engl J Med, 23, 2598, 2005.  The 48 months data has been published in Diabetologia, 53, 614-623, 2010 (www.diabetologia-journal.org).

About DEFEND

DEFEND-1 is a randomized, placebo-controlled Phase 3 study that has achieved its target enrollment of 240 patients, age 12 to 45, with newly diagnosed autoimmune type 1 diabetes.  DEFEND is being conducted at over 100 centers throughout Europe and North America.  The study is designed to evaluate whether a single course of otelixizumab, administered not more than 90 days after the initial diagnosis of autoimmune type 1 diabetes, will preserve beta cell function as measured by C-peptide, a surrogate measure of beta cell function.  The primary endpoint is measurement of C-peptide 12 months after study drug administration.  DEFEND-1 completed enrollment in January 2010, and will be confirmed in a second pivotal study, DEFEND-2.  For more information about DEFEND, please visit www.DefendAgainstDiabetes.com.

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 (sugar) level.  There are two major types of diabetes:  type 1 and type 2. Type 1, previously known as juvenile diabetes or insulin-dependent diabetes, is a disorder involving the body's immune system.  In type 1 diabetes, the immune system attacks and destroys the insulin-producing beta cells in the pancreas.  As a result of the decrease in endogenous (natural) insulin production, patients must monitor their glucose levels frequently and administer insulin regularly to control their blood glucose levels.  

About Otelixizumab

Otelixizumab is a targeted T cell immunomodulator being developed for the treatment of type 1 diabetes and other autoimmune diseases.  Otelixizumab targets CD3, a T lymphocyte receptor involved in normal cell signaling.  Otelixizumab has not yet been approved for marketing. Data suggest that the antibody may work in patients with type 1 diabetes who have residual beta cells by blocking the function of effector T cells that mistakenly attack and destroy insulin-producing beta cells, while stimulating regulatory T cells that are understood to protect against effector T cell damage, thus preserving the beta cells' ability to make insulin.  

About Tolerx

Tolerx, Inc., a world leader in the understanding of T cell function, is developing novel therapies intended to treat autoimmune diseases, diabetes, and cancer by specifically modulating T cell activity.  The company's pipeline includes its lead candidate, otelixizumab, a targeted T cell immunomodulator in Phase 3 development for the treatment of type 1 diabetes that is partnered with GlaxoSmithKline.  TRX1, a Phase 1 candidate, is a nonlytic anti-CD4 antibody that is being developed for the treatment of aberrant or untoward immune responses, and there are three pre-clinical candidates, TRX518, TRX585 and TRX385, that enhance immune responses and as such are being evaluated for potential benefit in the treatment of cancer and chronic infections. Tolerx is a privately held company headquartered in Cambridge, MA USA.  For more information, please visit www.tolerx.com.

SOURCE Tolerx, Inc.

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