Press Releases
Xencor Determines Structure Of Baff, A Key Autoimmune Disease Target
Discovery Enables Dominant Negative Inhibitor Strategy and
Clarifies BAFF Structural Controversy
Monrovia, CA – January 28, 2004 – Xencor, a drug discovery company,
today reported the structure of BAFF, also call BLyS or TALL-1, a key
regulator of immune function and an important target in autoimmune
disease. Scientists from Xencor demonstrated that BAFF's biologically
active form is trimeric, similar to other members of the TNF
superfamily of proteins. This work resolves conflicting reports in the
field and enables the discovery of novel inhibitors of BAFF using
Xencor's proprietary Dominant Negative strategy. This report was
published in today's issue of Nature.
“This basic research effort to characterize BAFF demonstrates Xencor's
commitment to the TNF superfamily of drug targets and our capabilities
in protein biophysics,“ said Bassil Dahiyat, Ph.D., Chief Scientific
Officer of Xencor. “Demonstrating that BAFF is trimeric is a key step
in our Dominant Negative BAFF inhibitor program, which is creating
inhibitors of BAFF to treat autoimmune diseases such as lupus, multiple
sclerosis and rheumatoid arthritis. BAFF is an exciting target and our
Dominant Negative mechanism offers important safety and efficacy
advantages in dealing with its complex biology by creating receptor
specific inhibitors.“ Dr. Dahiyat added, “We are using the Dominant
Negative strategy to create new therapeutic candidates and novel
intellectual property for several targets in the TNF superfamily,
including TNF alpha, RANKL and CD40L.“
About Dominant Negative Cytokine Modulators
Xencor has created inhibitors of Tumor Necrosis Factor (TNF), a key
target in arthritis and other rheumatic disorders, that have a unique
and proprietary Dominant Negative (DN) mechanism of action, distinct
from existing soluble receptor and neutralizing antibody approaches.
The DN mechanism enables a broad new opportunity to compete in the rich
TNF superfamily of drug targets for autoimmune disease and cancer,
which includes BAFF/BLyS, CD40L, RANKL and OX40L. DN molecules offer
receptor and ligand specificity, high stability, ease of production,
and a distinct intellectual property position.
About Protein Design Automation (PDA) technology
PDA technology combines high performance computing with sensitive
biochemical assays to create broader protein diversity with far greater
control than other optimization technologies, such as directed
evolution and phage display. It uses the information embedded in
protein structure to optimize protein activity, binding affinity and
specificity, stability, expression level, and potency. This process
also creates new intellectual property, continually broadening Xencor's
patent portfolio by generating sets of novel protein sequences that are
distinct from naturally occurring proteins.
About Xencor
Xencor is a preclinical-stage company that discovers and develops
protein therapeutics using its proprietary rational protein design
platform. Xencor's platform applies high performance computing and
advanced molecular biology to rapidly discover drug candidates with
novel mechanisms and improved safety and efficacy. Xencor is a
privately held biopharmaceutical company located in Monrovia, Calif.
Additional information is available at www.xencor.com.