NEWS-ZymoGenetics Presents Results of Healthy Volunteer Study with TACI-Ig at 4th International Congress on Autoimmunity

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ZymoGenetics Presents Results of Healthy Volunteer Study with TACI-Ig at 4th

International Congress on Autoimmunity

SEATTLE--(BUSINESS WIRE)--Nov. 8, 2004--ZymoGenetics, Inc. (Nasdaq:ZGEN)

today announced the results of a healthy volunteer study with TACI-Ig, a

potential therapy for autoimmune diseases and B-cell malignancies, which

were presented at the 4th International Congress on Autoimmunity in

Budapest, Hungary, on Saturday, November 6. The study results indicated that

TACI-Ig was safe and well tolerated at all dose levels tested.

In the dose escalation study, designed to assess the safety and

pharmacokinetics of TACI-Ig, twenty-three healthy male subjects aged 19 to

44 years were assigned to one of four treatment cohorts, then were

randomized in a double-blinded manner to receive a single subcutaneous

injection of either TACI-Ig or placebo. Dose levels ranged from 2.1 to 630

milligrams. Follow-up evaluations were conducted over a seven-week period

both to assure safety and to meet study objectives.

" We are encouraged by the results from the TACI-Ig healthy volunteer study, "

said Jan K. Ohrstrom, M.D., Senior Vice President and Chief Medical Officer

of ZymoGenetics. " Even at high doses, TACI-Ig appeared to be safe and well

tolerated. We now have a number of clinical studies underway for TACI-Ig in

patients with autoimmune diseases such as lupus and rheumatoid arthritis and

will have studies starting this quarter for patients with B-cell

malignancies. "

Summary results and conclusions of the study were as follows:

Results

The nature, incidence and severity of adverse events were comparable between

TACI-Ig treatment groups and placebo. No serious adverse events were

reported, no subjects were withdrawn from the study as a result of adverse

events, and there were no clinically significant changes in other measured

safety parameters.

TACI-Ig reached maximum serum concentrations between 16 and 20 hours after

dosing. Serum levels increased with the dose escalation. Immunoglobulin M

(IgM) levels declined after TACI-Ig doses of 70, 210 and 630 mg, with no

discernible effects on IgG levels or lymphocyte populations.

Conclusions

At all doses, TACI-Ig was shown to be safe and well tolerated in healthy

volunteers. The observed treatment-dependent decline in IgM levels was

consistent with the expected pharmacological activity of TACI-Ig and helps

to establish its potential to suppress the formation of autoantibodies.

Study results support further clinical evaluation of TACI-Ig in the

treatment of autoimmune diseases and other B-cell disorders. Phase 1b

studies in patients with SLE, rheumatoid arthritis, and in patients with

B-cell malignancies are in progress.

About TACI-Ig

TACI-Ig is a recombinant fusion protein containing the extracellular ligand

binding portion of the TACI receptor and the Fc portion of human

immunoglobulin G (IgG). TACI-Ig is being developed for the treatment of

autoimmune diseases, including systemic lupus erythematosus and rheumatoid

arthritis, as well as for other B-cell disorders, including B-cell

malignancies.

TACI-Ig binds to BLyS and APRIL, TNF family cytokines that promote B-cell

survival and the production of harmful autoantibodies, which cause certain

autoimmune diseases such as systemic lupus erythematosus (SLE). Data from

ZymoGenetics and others indicate that levels of BLyS and APRIL, as well as

complexes containing both BLyS and APRIL, are elevated in rheumatoid

arthritis. TACI-Ig has been shown to affect several stages of B-cell

development and may inhibit the survival of cells responsible for making

antibodies. ZymoGenetics is developing TACI-Ig in collaboration with Serono

S.A. Phase 1b studies in patients with SLE, rheumatoid arthritis, and in

patients with B-cell malignancies are in progress.

ZymoGenetics received clearance from the Food and Drug Administration in

October 2004 to initiate studies with TACI-Ig in patients with advanced

B-cell malignancies. These include chronic lymphocytic leukemia and B-cell

non-Hodgkin's lymphoma. In the U.S., over 320,000 people are estimated to

have some form of these B-cell cancers, and each year approximately 55,000

new cases and 20,000 deaths occur from these cancers. Between 80% and 85% of

non-Hodgkin's lymphomas are of B-cell origin. TACI-Ig is presumed to affect

these malignancies by inhibiting BLyS and APRIL, members of the tumor

necrosis factor family that appear to enable malignant B cells to survive.

ZymoGenetics and Serono Collaboration

ZymoGenetics and Serono entered into an exclusive co-development and

commercialization agreement in 2001 focused on the development of TACI-Ig.

The two companies share research and development expenses worldwide, except

for in Japan, where Serono covers all expenses. ZymoGenetics retains the

option to co-promote products with Serono in North America. If ZymoGenetics

exercises that option, the two companies will share commercialization

expenses and profits equally. Serono has exclusive rights to market TACI-Ig

in the remainder of the world, for which ZymoGenetics will receive royalty

payments for any such sales. Serono is responsible for manufacturing the

product for both clinical trials and commercial sale. Recently, the

companies announced an expansion of their relationship in an alliance

separate from the TACI-Ig development collaboration.

About ZymoGenetics

ZymoGenetics is a biopharmaceutical company focused on the discovery,

development and commercialization of therapeutic proteins for the prevention

or treatment of human diseases. The Company is developing a diverse pipeline

of potential proprietary product candidates that are moving into and through

clinical development. These span a wide array of clinical opportunities that

include bleeding, autoimmune diseases and cancer. ZymoGenetics intends to

commercialize these product candidates through internal development,

collaborations with partners, and out-licensing of patents from its

extensive patent portfolio. For further information, visit

www.zymogenetics.com.

This press release contains " forward-looking statements " within the meaning

of the Private Securities Litigation Reform Act of 1995. These

forward-looking statements are based on the current intent and expectations

of the management of ZymoGenetics. These statements are not guarantees of

future performance and involve risks and uncertainties that are difficult to

predict. ZymoGenetics' actual results and the timing and outcome of events

may differ materially from those expressed in or implied by the

forward-looking statements because of risks associated with our unproven

discovery strategy, preclinical and clinical development, regulatory

oversight, intellectual property claims and litigation and other risks

detailed in the company's public filings with the Securities and Exchange

Commission, including the company's Annual Report on Form 10-K for the year

ended December 31, 2003. Except as required by law, ZymoGenetics undertakes

no obligation to update any forward-looking or other statements in this

press release, whether as a result of new information, future events or

otherwise.

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