Tolerx, Inc. Advancing Novel Type 1 Diabetes Agent into Phase III Clinical Trial Program Following End of Phase II FDA Meeting
The Phase III study, known as DEFEND (Durable Response Therapy Evaluation For Early or New Onset Type 1 Diabetes), will be conducted at multiple centers in North America and Europe and will evaluate whether a single course of otelixizumab reduces the amount of administered insulin required for control of blood glucose levels by inhibiting destruction of beta cells. Maintenance of beta cell function has been associated with improved glycemic control (HbA1c levels), fewer hypoglycemic events and reduction of long term disease complications in established diabetics in the Diabetes Control and Complications Trial (DCCT). DEFEND enrollment is expected to begin mid-2008.
"We are very pleased with the outcome of the End of Phase II meeting with FDA and the opportunity to advance initiation of the DEFEND trial. This step is a significant and important milestone for Tolerx," said Dr. Douglas J. Ringler, President and Chief Executive Officer of Tolerx. "The rigorous science behind our Phase II clinical program has provided us with valuable insights that facilitated our moving forward into DEFEND with an optimized dosing regimen that has the potential to transform the treatment paradigm for type 1 diabetes."
"We have worked closely with FDA over several years to ensure that the design and endpoints of DEFEND reflect the mechanism of action of otelixizumab and are relevant and appropriate in evaluating whether otelixizumab may benefit subjects with new-onset type 1 diabetes. In February, 2008 FDA released new draft guidance on developing drugs for diabetes mellitus and DEFEND incorporates key measures described within the guidance, in particular, stimulated C-peptide levels as a primary efficacy endpoint," said Dr. Lou Vaickus, Chief Medical Officer at Tolerx.
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) levels. 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 of the body's immune system. In type 1 diabetes, the immune system attacks and destroys the insulin-producing beta cells in the pancreas. The decrease in endogenous (natural) insulin production necessitates the need for type 1 patients to monitor glucose levels frequently and administer insulin therapy frequently to control their blood glucose levels.
Otelixizumab is a monoclonal antibody that binds to CD3, a T lymphocyte receptor involved in normal cell signaling. Otelixizumab is thought to work by blocking the function of T effector cells that attack the body's tissues and cause autoimmune disease while inducing a subset of T cells known as T regulatory cells. It is thought that the T regulatory cells may protect against T effector cell damage well after the drug has been eliminated from the body. Tolerx is continuing to evaluate otelixizumab in subjects with type 1 diabetes in TTEDD (TRX4 Therapeutic Evaluation of Different Dosing Regimens), an ongoing Phase II study. A principal purpose of TTEDD was to evaluate different dosing regimens in an effort to reduce side effects and to learn more about otelixizumab's activity. Tolerx has conducted dose optimization studies in type 1 diabetes and has identified a dosing regimen that thus far has significantly reduced side effects while maintaining important biological activity. This dosing regimen will be used in our Phase III pivotal trial DEFEND.
Tolerx Collaboration with GlaxoSmithKline
In October 2007, Tolerx and GlaxoSmithKline (GSK) entered into a global alliance to develop and commercialize otelixizumab in numerous indications, including type 1 diabetes. Under the terms of the agreement, Tolerx is responsible for conducting the Phase III clinical program for type 1 diabetes in the US and if successful, for submitting the biologics license application (BLA) to the FDA. Tolerx has the option to co-promote otelixizumab in type 1 diabetes in the US with GSK while GSK has exclusive rights to develop and commercialize otelixizumab in all other indications worldwide, including pediatric type 1 diabetes.
Tolerx is a biopharmaceutical company engaged in the discovery and development of novel therapies for immune-mediated diseases. Tolerx currently has two antibodies in clinical development: otelixizumab and TRX1. TRX1 is a humanized anti-CD4 monoclonal antibody being developed in collaboration with Genentech, Inc. Tolerx is also engaged in preclinical development of new product candidates that circumvent immune system tolerance. These product candidates are being evaluated for the treatment of cancer or chronic viral diseases. For more information, please visit http://www.tolerx.com.
Tolerx Forward-Looking Statements
This press release contains certain statements that are preceded by, followed by, or that include the words "will," "is expected to," "may," "toward," "has the potential to," "whether" or similar expressions or the negation thereof, Such statements, which are not historical facts, constitute "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 (the "Reform Act"). Statements regarding the outcomes sought to be realized in the phase III clinical trial, the possibility that otelixizumab may have the potential to change type I diabetes treatment paradigms, the anticipated progress and development of otelixizumab, in type 1 diabetes and other disease indications, are all forward-looking statements. Such forward-looking statements involve risks, uncertainties and other factors that may cause the actual performance or achievements of Tolerx to be materially different from any future results, performance, or achievements expressed or implied by such forward-looking statements. Factors and risks that may impact management's expectations and affect the forward- looking statements shall include but not be limited to results of DEFEND and other future clinical studies, the ability to obtain regulatory approval for otelixizumab for type 1 diabetes or any other indication, the continuation of the collaboration with GSK, the introduction of competing therapies by other companies and changes in the company's business plan or objectives. These statements reflect the view of Tolerx as of the date of this press release and should not be relied upon as reflecting the company's views at any date subsequent to this release. Tolerx undertakes no obligation to update or revise any forward-looking statements to reflect events or circumstances after the date of this press release.
Source: Tolerx, Inc.