http://news.excite.com/news/pr/010904/wa-zymogenetics
Sept. 4, 2001
ZymoGenetics and Serono S.A. (SWX
Swiss Exchange: SEO and NYSE: SRA) announced that they have entered into
an exclusive co-development and commercialization agreement focused on
two preclinical product candidates derived from ZymoGenetics' discovery
research. Using a genomics-driven approach, ZymoGenetics' scientists identified
the two molecules, termed TACI and BCMA, as key regulators of the human
immune system. These two proteins are cell-surface receptors found on B-lymphocytes,
cells involved in the production of antibodies.
The companies intend to focus their
activities on the development of one or more products based on these receptors
for the treatment of autoimmune diseases where there is an over production
of autoantibodies (antibodies that attack one's own cells). Serono has
extensive experience in the research and treatment of autoimmune diseases
such as multiple sclerosis and rheumatoid arthritis, where there remain
significant unmet medical needs.
"This exciting collaboration with
Serono underscores the power of ZymoGenetics' product discovery engine,"
stated Bruce L.A. Carter, Ph.D., President and Chief Executive Officer
of ZymoGenetics. "In addition to working with a world leader in the development
of protein therapeutics we will also benefit from Serono's long-standing
expertise as we build our own clinical development and manufacturing capabilities
here at ZymoGenetics."
"The agreement between Serono and
ZymoGenetics is another example of Serono's collaborative approach to access
novel protein based therapeutic technologies and emphasizes our commitment
to the treatment of autoimmune and serious inflammatory diseases," commented
Silvano Fumero, Head of Research and Pharmaceutical Development at Serono.
"ZymoGenetics' expertise in functional genomics combined with our own experience
in product development and commercialization will help take these preclinical
product candidates through development."
Under the terms of the agreement,
ZymoGenetics could receive license fees and milestone payments of up to
$52.5 million linked to the development and approval of products. The two
companies will share research and development expenses worldwide, excluding
Japan where Serono will cover all expenses. ZymoGenetics retains an option
to co-promote products with Serono in North America. If ZymoGenetics exercises
this option the two companies will share commercialization expenses and
profits equally. Serono will have exclusive rights to market products in
the remainder of the world, for which ZymoGenetics will receive undisclosed
royalties. Serono will manufacture all products for both clinical trials
and commercial sale.
"A key component of this agreement
is ZymoGenetics' participation in the sales and marketing of products resulting
from the collaboration," Dr. Carter added. "We see this as critical to
the long-term development of our business. Our ultimate goal is to be a
fully integrated company that spans from initial drug discovery to the
sale of biopharmaceutical products. By partnering with Serono, we believe
that we have enhanced our efforts toward this goal."
BACKGROUND INFORMATION
Autoimmune Disease Progression
One of the key components of the
autoimmune disease process is the development of antibodies to an individual's
own healthy tissues. When normal immune function goes awry due to altered
development, inherited disorders or environmental factors, the body's B
cells (B lymphocytes) produce "autoantibodies." These autoantibodies then
attack the individual, leading to destruction of specific tissues. Depending
upon the type of autoimmune disorder, targeted tissues may be the kidney,
as in systemic lupus erythematosus (SLE); the muscle system, as in myasthenia
gravis; the nervous system, as in multiple sclerosis; or portions of the
joint, as in rheumatoid arthritis. Currently available treatments for these
conditions are often limited due to toxic side effects, including their
overall suppressive effects on the human immune system. New therapies that
act specifically on destructive B cell pathways provide a novel opportunity
to improve patient outcomes.
TACI and BCMA Product Candidates
The two product candidates, TACI
and BCMA, are receptors found on B cells, that when stimulated, induce
the production of antibodies. In the case of autoimmune disease these are
autoantibodies (antibodies that attack one's own cells). Using their bioinformatics
gene discovery platform, scientists at ZymoGenetics initially identified
a growth factor called BlyS (also known as BAFF, TALL-1, THANK and zTNF4)
that is a key mediator in regulating the human immune system. This factor
was found to bind to B cells, stimulating the replication and survival
of these cells, and inducing their production of antibodies.
Using their expertise in pairing
growth factors with their corresponding receptors, the ZymoGenetics scientists
subsequently identified two receptors, TACI and BCMA, that are found on
the surface of B cells and that bind BLyS. These receptors also bind a
second growth factor called APRIL. The importance of this pathway for regulating
B cell function is demonstrated in a recent publication from ZymoGenetics(1)
where the gene for BLyS was eliminated in mice, thereby preventing the
production of BLyS protein. These mice had virtually no mature B cells
present and had reduced serum antibody response to immunization. ZymoGenetics
scientists further showed that mice genetically engineered to over express
the gene for BlyS develop symptoms of the autoimmune disease systemic lupus
erythematosus (SLE), including the generation of autoantibodies(2). Reports
from ZymoGenetics and others have also demonstrated an association between
elevated levels of circulating BLyS and autoimmune disease, including SLE
in mice and humans and rheumatoid arthritis in humans.
By using the receptor portions of
TACI and BCMA responsible for binding the growth factors, ZymoGenetics
researchers have produced antagonist proteins that can "mop up" increased
BLyS and APRIL growth factor present in the blood. Such a soluble TACI-
or BCMA- molecule thus prevents binding of the growth factors to the B
cells, regulating the development of mature B cells and antibody production.
In published studies(1), scientists at ZymoGenetics demonstrated that in
TACI transgenic mice, mice that have been genetically engineered to over
express a soluble form of the TACI receptor, there are fewer mature B cells
and reduced levels of circulating antibody. Similar results were observed
in normal mice treated with soluble TACI receptor.
Through the ability of soluble receptors
to bind to and eliminate the BLyS and APRIL growth factors and consequently
avert production of destructive autoantibodies, it may be possible to limit
the extent of tissue damage observed in patients with autoimmune disease.
In animal models of SLE, for example, scientists at ZymoGenetics demonstrated
that a soluble form of TACI- receptor was effective in limiting progression
of the disease (2). Similarly, in a mouse model of collagen-induced arthritis,
ZymoGenetics scientists demonstrated that treatment with soluble TACI-receptor
was able to inhibit the development of collagen-specific antibodies and
the incidence of disease (1).
1. Immunity, 15;289-302,2001
About ZymoGenetics
ZymoGenetics is an independent biopharmaceutical
company focused on the discovery and development of protein therapeutics
for the prevention or treatment of significant human diseases. Using its
proven product discovery engine, comprising genomics, bioinformatics, protein
chemistry and preclinical biology, ZymoGenetics has generated a broad pipeline
of proprietary product candidates. ZymoGenetics will commercialize these
products through internal development, collaborations with biopharmaceutical
partners, and out-licensing of its extensive patent portfolio. For further
information, visit www.zymogenetics.com.
About Serono
Serono is a global biotechnology
leader. The Company has six recombinant products on the market, Gonal-F
(R), Luveris (R), Ovidrel(R), Rebif(R), Serostim (R) and Saizen (R), (Rebif
(R) and Luveris (R) are not approved in the USA). In addition to being
the world leader in reproductive health, Serono has strong market positions
in neurology, metabolism and growth. The Company's research programs are
focused on growing these businesses and on establishing new therapeutic
areas. Currently, there are thirteen molecules in development.
In 2000, Serono achieved worldwide
revenues of US$1.240 billion, and a net income of US$301 million, making
it the third largest biotech company in the world based on revenues. The
Company operates in 45 countries, and its products are sold in over 100
countries. Bearer shares of Serono S.A., the holding company, are traded
on the SWX Swiss Exchange (SEO) and its American Depositary Shares are
traded on the New York Stock Exchange (SRA).
Some of the statements in this press
release are forward looking. Such statements are inherently subject to
known and unknown risks, uncertainties and other factors that may cause
actual results, performance or achievements of Serono S.A. and affiliates
to be materially different from those expected or anticipated in the forward-looking
statements. Forward-looking statements are based on Serono's current expectations
and assumptions, which may be affected by a number of factors, including
those discussed in this press release and more fully described in Serono's
Annual Report on Form 20-F filed with the U.S. Securities and Exchange
Commission on April 23, 2001. These factors include any failure or delay
in Serono's ability to develop new products, any failure to receive anticipated
regulatory approvals, any problems in commercializing current products
as a result of competition or other factors, our ability to obtain reimbursement
coverage for our products, and government regulations limiting our ability
to sell our products. Serono has no responsibility to update the forward-looking
statements contained in this press release to reflect events or circumstances
occurring after the date of this press release.
Contact Information:
For ZymoGenetics, Inc.:
For Serono:
Serono International S.A., Geneva
Switzerland
SEATTLE, and GENEVA
PRNewswire
2. Nature 404;995-999, 2000
Charles Hart
Sr. Director, Corporate Communications
&
Investor Relations
ZymoGenetics, Inc.
(206) 442-6600
www.zymogenetics.com
Sharon Karlsberg
Director
Feinstein Kean Healthcare
(617) 577-8110
www.fkhealth.com
Media Relations
Tel: +41-22-739 36 00
Fax: +41-22-739 30 85
Investor Relations
Tel: +41-22-739 36 01
Fax: +41-22-739 30 22
Reuters: SEOZ.VX
Bloomberg: SEO VX
EQUITY/ SRA US
Serono, Inc., Norwell, MA
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Fax: +1 781 982 1369
www.seronousa.com
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www.noonanrusso.com.