More MS news articles for Sep 2001

ZymoGenetics and Serono to Collaborate on a Novel Therapeutic Approach For Autoimmune Disease

http://news.excite.com/news/pr/010904/wa-zymogenetics

Sept. 4, 2001
SEATTLE, and GENEVA
PRNewswire

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
2. Nature 404;995-999, 2000

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.:
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

For Serono:

Serono International S.A., Geneva Switzerland
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
Media Relations
Tel: +1 781 681 2340
Fax: +1 781 982 1369
www.seronousa.com
Noonan/Russo Communications
Tel: +44-20 7726 4452
Fax: +44-20 7726 4453
www.noonanrusso.com.