Released on: June 10, 2008, 2:24 pm

Press Release Author: GTCbio

Industry: Biotech

Press Release Summary: Xiang Yang Tan, Lab Head at Wyeth Pharmaceuticals to Present
at GTCbio's 2nd Protein Therapeutics Discovery & Development Conference on September
8-9, 2008 in San Diego, CA

Press Release Body:
MONROVIA, CA - Dr. Xiang Yang Tan, Lab Head at Wyeth Pharmaceuticals will be
speaking at GTCbio's 2nd Protein Therapeutics Discovery & Development conference on
September 8-9, 2008 in San Diego, CA. Dr. Tan will present on development of novel
therapeutic antibodies for the treatment of sepsis.
Sepsis is an inflammatory response to an infection or stimulus that becomes
amplified and dysregulated. Despite recent market entries and continually improving
hospital care, sepsis remains a significant unmet medical need. More than 2 million
cases of sepsis occur each year in the U.S., Europe and Japan, with estimated annual
costs of $17 billion and mortality rates ranging from 20-50%. Safe and
well-tolerated therapeutic agents that could reduce the progression from early
sepsis to severe sepsis or septic shock, and thereby improve survival, could provide
a break-through in sepsis therapy. The receptor for advanced glycation end products
(RAGE) is a cell-surface member of the immunoglobulin super-family, which binds with
multiple ligands, such as HMGB1, A-beta and S100. RAGE was originally identified by
its ability to bind advanced glycation end-products (AGEs) that are produced by
glycoxidation of proteins. RAGE and its ligands are elevated in a number of disease
settings such as sepsis, atherosclerosis and vascular complications secondary to
diabetes. Data generated at Wyeth indicates that RAGE may play an important role in
the pathogenesis of sepsis. Homozygous RAGE null mice (RAGE-/-) showed a significant
degree of protection from the lethal effects of cecal ligation and puncture (CLP), a
murine model of sepsis, when compared to parental, wild type mice. In addition, an
anti-RAGE antibody designated XT-M4 was generated in Wyeth. XT-M4 recognized RAGE
with high affinity and blocked RAGE and ligands interactions. XT-M4 showed efficacy
in the CLP model when delivered at the time of surgery or delayed to 24 hours
post-CLP. In a second model, inhibition of RAGE or deletion of RAGE did not disrupt
the host mechanism or clearance of microbial pathogens. These studies demonstrated
that RAGE is involved in the septic response and an anti-RAGE antibody can improve
survival in polymicrobial sepsis in mice.
XT-M4 was fully humanized to decrease any potential immunogenicity and
manufacturability issues. The humanized XT-M4 retained full binding activity and was
administered in a prophylactic study in mouse CLP. A single intravenous dose
protected about 90% of mice seven days post-CLP.

D. Yang Tan will provide highlights on why sepsis remains a significant unmet
medical need with mortality rates ranging from 20-50%, and share how the receptor
for advanced glycation end-products (RAGE) plays an important role in the
pathogenesis of sepsis, RAGE antibody XT-M4 showed significant protection of the
mice from the lethal effects of a murine model of sepsis, cecal ligation and
puncture (CLP) and provide examples on how XT-M4 was fully humanized to decrease any
potential immunogenicity and manufacturability issues.

GTCbio's 2nd Annual Protein Therapeutics Discovery and Development Conference will
explore the therapeutic applications of proteins, with a look at discovery and
design of therapeutics, overcoming challenges associated with protein based drugs,
and new tools and strategies in process development. Finally, attendees will get an
update on novel developments in protein therapeutics. The keynote presentation will
be given by Dr. Michael Hanley, Vice President of Discovery Research & CSO of Amylin
Pharmaceuticals.

For more information including a detailed agenda, exhibitor opportunities and
registration information visit http://gtcbio.com/conferenceDetails.aspx?id=128.
ABOUT GTCbio
GTCbio organizes conferences specifically for the biomedical and biopharmaceutical
industries. Our goal is to facilitate the exchange of biopharmaceutical and
biomedical intelligence between industry leaders, academic and government
organizations, and the financial community.
GTCbio is a subsidiary of Global Technology Community, LLC, a privately held company
founded in 2002.


Web Site: http://www.gtcbio.com

Contact Details: Contact: GTCBIO (626) 256-6405, (626) 256-6460 fax,
jason.yi@gtcbio.com
434 W. Foothill Blvd.
Monrovia, CA 91016