ZymoGenetics to Begin Clinical Studies with Recombinant Human Thrombin.

Business Editors/Health/Medical Writers

SEATTLE--(BUSINESS WIRE)--Dec. 3, 2003

Update provided on acquired Factor XIII deficiency program and

upcoming presentations of clinical trial results at the American

Society of Hematology Meeting

ZymoGenetics (Nasdaq:ZGEN) today announced that it received agreement from the Food and Drug Administration (FDA) to initiate clinical studies with recombinant human Thrombin (rhThrombin). rhThrombin is being developed by ZymoGenetics for the control of bleeding associated with surgical procedures. The company expects to open enrollment and begin treating patients for the dose escalation portion of a Phase 1/2 study in spinal surgery by the end of the year.

"With the entry of rhThrombin into clinical development, we have met our goal of commencing clinical studies with three separate proteins in 2003," commented Bruce L. A. Carter, Ph.D., President and Chief Executive Officer of ZymoGenetics. "The study that we are about to begin is the dose escalation component of a planned Phase 1/2 study in which we intend to evaluate the safety and efficacy of rhThrombin in spinal surgery. We expect to conduct additional concurrent Phase 2 studies in other surgical indications in 2004 with the aim of obtaining a broad label for the product as a general hemostat."

Thrombin is used in over 500,000 surgeries per year in the United States. Currently, only thrombin derived from bovine blood is available in the US as a stand-alone thrombin product. Bovine-derived thrombin has been associated with the development of antibodies that may cross-react with human blood proteins. In some cases, these antibodies lead to serious bleeding complications. The company believes that rhThrombin will be preferred as an alternative to the bovine-derived product.

rFactor XIII Presentations at American Society of Hematology (ASH)

Results from three Phase 1 clinical studies, conducted by ZymoGenetics with recombinant human Factor XIII (rFactor XIII), will be presented at the American Society of Hematology (ASH) meeting that is taking place in San Diego from December 5-9, 2003. Factor XIII is a protein involved in the stabilization and strengthening of blood clots and is being developed by ZymoGenetics for the treatment of bleeding complications associated with congenital and acquired Factor XIII deficiencies.

"The studies that will be reported on at the ASH meeting highlight the progress that we have achieved this year in our rFactor XIII development program," stated Jan K. Ohrstrom, M.D., Senior Vice President and Chief Medical Officer of ZymoGenetics. "Not only does our rFactor XIII product candidate appear safe in the populations studied, but we observed an increase in clot strength and stability measured in vitro following rFactor XIII administration in patients with congenital Factor XIII deficiency."

Abstract presentations include:

-- "Safety and pharmacokinetics of recombinant Factor XIII in

patients with congenital Factor XIII deficiency," -- poster

presentation by Amy Lovejoy, M.D., Saturday, Dec. 6 at 6:00 pm

(Abstract 1002). The study was conducted at Children's

Hospital of Orange County (CHOC) in California. Congenital

Factor XIII deficiency is associated with severe bleeding

tendency and affected individuals have a high risk of bleeding

into the brain and in soft tissues. Recombinant Factor XIII is

being developed as a treatment for those individuals.

-- "Phase 1 pharmacokinetics of a single dose of recombinant

Factor XIII administered to healthy volunteers," -- poster

presentation by Jennifer Visich, Ph.D., Saturday, Dec. 6 at

6:00 pm (Abstract 1104). This study found that rFactor XIII

has a half-life of 9-13 days, similar to native Factor XIII,

supporting the intended once monthly dosing regimen in

congenitally deficient patients.

-- "A randomized, placebo-controlled, double-blind, multi-dose

study of the safety and pharmacokinetics of recombinant Factor

XIII administration in healthy volunteers," -- publication

only presentation by Tom Reynolds, M.D., Ph.D., (Abstract

4100). Subjects in this study received daily dosing of rFactor

XIII for five days.

To date, over 60 subjects have been treated with rFactor XIII in the three Phase 1 studies. No serious adverse events were observed with rFactor XIII treatment in any of the studies. The results from these studies suggest that rFactor XIII can be safely administered, both as a single administration and in repeat administrations over a 5-day period.

Status of rFactor XIII Acquired Deficiency Program

In addition to developing rFactor XIII as a therapeutic for the treatment of individuals with congenital Factor XIII deficiency, ZymoGenetics intends to develop rFactor XIII for indications where there is an acquired Factor XIII deficiency. An example where this occurs is in patients undergoing a coronary bypass procedure. In these individuals the levels of circulating Factor XIII have been observed to decrease to approximately 50% of normal and have been associated with post-operative bleeding. ZymoGenetics intends to test rFactor XIII in this patient population as a treatment to prevent bleeding complications.

The company recently disclosed that it had filed an Investigational New Drug application with the FDA to test rFactor XIII in patients undergoing a coronary bypass procedure and that it was the goal of the company to begin treating patients in this study by the end of 2003. The company has been asked by the FDA to provide additional data in support of the proposed study, which will delay the initiation of the study into 2004.

Upcoming Event

On December 11, 2003, ZymoGenetics will hold an Analyst & Investor Briefing at the Four Seasons Hotel, 57 East 57th Street, in New York City from 9:30 am to 1:00 pm. At this briefing the company will provide detailed updates for their four lead product candidates: rFactor XIII, rhThrombin, TACI-Ig and IL-21. To attend this session, contact Susan Specht, phone [phone].

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. Using a product discovery engine that combines ZymoGenetics' strengths in biology, protein chemistry, molecular and cellular biology and bioinformatics, ZymoGenetics is developing a pipeline of potential proprietary product candidates. These span a wide array of clinical opportunities, including cardiovascular disease, autoimmune disease, cancer and tissue repair. 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, 2002, and its prospectus supplement filed with the Commission on October 16, 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.