Collaboration Focuses on Type 1 Diabetes and Other Autoimmune Indications
London, UK and Cambridge, MA - October 23, 2007 - GlaxoSmithKline
and Tolerx, Inc. today announced the execution of a worldwide alliance
to develop and commercialize otelixizumab (TRX4), a novel humanized
anti-CD3 monoclonal antibody that has potential across a broad range of
autoimmune and immune-mediated inflammatory diseases, including type 1
diabetes. Otelixizumab has been evaluated in type 1 diabetes in two
Phase II studies and in psoriasis in two Phase I studies. In clinical
trials, otelixizumab has been shown to preserve the function of
insulin-producing beta cells in the pancreas in patients with type 1
diabetes, reducing the amount of administered insulin needed to control
blood glucose levels.
Under the terms of the agreement, Tolerx will have responsibility for
the Phase III clinical program for type 1 diabetes in the US up to and
including regulatory submission of the biologics license application
(BLA). Tolerx has the option to co-promote otelixizumab in type 1
diabetes in the US with GSK, while GSK will have exclusive rights to
develop and commercialize otelixizumab in all other indications in the
rest of the world. GSK also has the exclusive right to develop the
pediatric indication for type 1 diabetes in the US.
As part of the collaboration, Tolerx will receive an upfront
payment, equity and advance R&D funding totaling $70 million. In
addition, Tolerx may receive up to $155 million in future development
costs of otelixizumab in type 1 diabetes. Tolerx may earn up to $350
million in milestone payments, assuming successful development and
approvals of otelixizumab for type 1 diabetes and multiple additional
indications. Tolerx may also receive up to $175 million in sales
milestone payments based on tiered net sales thresholds of
otelixizumab. Tolerx will be entitled to receive tiered, double-digit
royalty payments on worldwide sales of otelixizumab in all indications.
At the time of an initial public offering of Tolerx’s common stock and
at the request of Tolerx and certain other conditions, GSK will invest
up to an additional $10 million in Tolerx’s common stock.
Dr. Moncef Slaoui, Chairman of Research and Development at GSK,
commented, “Otelixizumab is another welcome addition to GSK’s rapidly
expanding biopharmaceuticals pipeline. This is a key area of future
growth and investment for GSK and, as a novel treatment for many T
cell-mediated diseases, the potential of otelixizumab is significant.
Together with Tolerx, who are pioneers in this area of science, we hope
to realize the potential of this compound and bring a valuable new
treatment option to patients suffering from type 1 diabetes and other
autoimmune disorders.”
"GSK brings a wealth of experience, expertise, and global resources to
this collaboration. The agreement with GSK enables us to operationally
leverage Tolerx’s expertise in therapeutic immune regulation, expand
the development of otelixizumab in type 1 diabetes and other
indications, and capitalize on GSK’s considerable worldwide
development, regulatory, and commercialization infrastructure and
experience,” said Dr. Douglas J. Ringler President and Chief Executive
Officer of Tolerx. “Moreover, it provides the infrastructural support
required to advance our goal of being first-to-market with otelixizumab
in type 1 diabetes. We anticipate the collaboration will allow the
potential of this novel therapy to be fully explored globally, not only
for the treatment of patients with type 1 diabetes but also for those
with autoimmune disorders for which the current standard of care is
inadequate.”
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.
About Otelixizumab
Otelixizumab is a monoclonal antibody that binds to a receptor
component found on all T cells known as CD3, which is involved in
normal T cell signaling. Otelixizumab is designed to block the function
of autoreactive T-effector cells that attack the body’s tissues and
cause autoimmune disease while inducing a subset of T cells called
T-regulatory cells that are thought to protect against T-effector cell
damage well after the drug has been eliminated from the body. In a
Phase II clinical study of subjects with new-onset type 1 diabetes,
otelixizumab demonstrated the potential to preserve the function of
insulin-producing beta cells in the pancreas and reduce the amount of
administered insulin needed to control blood glucose levels for up to
18 months after only a single six day course of therapy. In the study,
residual beta cell function was assessed by measuring glucose
clamp-induced C-peptide release before and after the administration of
glucagon. Otelixizumab administration was associated with transient
symptoms of flu-like syndrome and transient Epstein-Barr Virus (EBV)
reactivation. Tolerx has completed dose optimization studies in
subjects with type 1 diabetes and psoriasis and has identified a dosing
regimen that thus far has significantly reduced or eliminated these
side effects while maintaining important biological activity.
