News Release

ZymoGenetics Interleukin 21 Phase 1 Data Presented at ASCO Annual Cancer Meeting; Interim Results Show Potential to Treat Metastatic Melanoma and Renal Cell Carcinoma

May 16, 2005

SEATTLE, May 16, 2005 (BUSINESS WIRE) -- ZymoGenetics, Inc. (Nasdaq:ZGEN) announced today that an oral presentation and two posters concerning Interleukin 21 (IL-21), a potential treatment for cancer, were given at the recent American Society of Clinical Oncology (ASCO) 2005 annual meeting held in Orlando, Florida. Brendan Curti, M.D., Providence Portland Medical Center, summarized results from the treatment of the first twelve patients in a Phase 1 study of IL-21 as treatment for metastatic melanoma and renal cell carcinoma. Dr. Curti reported that IL-21, administered in an outpatient setting, showed evidence of anti-tumor activity and was reasonably well tolerated with reversible toxicities. One patient with metastatic renal cell carcinoma achieved a partial response that continues at more than seven months of follow-up and six patients had at least stable tumor measurements after two cycles of treatment. No antibody response against IL-21 was detected, and there was dose dependent immune cell activation that was consistent with nonclinical studies. Dose escalation in the Phase 1 study is continuing to determine the maximally tolerated dose of IL-21.

"The interim IL-21 study results, although early, look promising," stated Bruce L.A. Carter, president and chief executive officer. "We were pleased to see evidence of anti-tumor activity with a tolerable side effect profile. Cancer patients need more effective treatments and we are hopeful about the potential of IL-21 as an outpatient treatment to help address this need," added Dr. Carter.

Primary objectives of the open label Phase 1 dose escalation study are to assess safety and determine the maximum tolerated dose of IL-21. Secondary objectives are to assess pharmacokinetics, immunogenicity and other clinical or biological parameters that may correlate with anti-tumor activity. All twelve patients treated had tumors that had metastasized (Stage IV); eight of the twelve had malignant melanoma and four had renal cell carcinoma. Two cycles of five daily intravenous doses of 3, 10 or 30 micrograms per kilogram were separated by a 9 to 16 day rest period. Two of the 12 patients were given two additional five-day cycles of IL-21, for a total of four cycles.

For patients receiving two dose cycles, all of the drug-related adverse events were mild to moderate and were completely reversible. One patient who received four cycles of treatment at the highest dose developed acute hepatic injury at the end of the fourth cycle, which resolved completely, with hepatic function returning to normal, after drug administration was stopped.

Dr. Curti's presentation, "Preliminary tolerability and anti-tumor activity of intravenous recombinant human Interleukin 21 (IL-21) in patients with metastatic melanoma and metastatic renal cell carcinoma," is listed as ASCO Abstract No: 2502.

In addition, the following two nonclinical IL-21 posters were presented at ASCO:

-- "Enhancement of trastuzumab-mediated cellular cytotoxicity by interleukin-21" Presenter: Cecile Krejsa, Ph.D. Poster Number: G16 Abstract No: 2567 Conclusion: Treatment with IL-21 increased the activity of mononuclear cells in trastuzumab-mediated ex vivo antibody dependent cell mediated cytoxicity (ADCC) assays. This lytic activation is consistent with the enhanced effector function observed after in vitro treatment of natural killer cells or mononuclear cells with IL-21. Thus, treatment with IL-21 may enhance trastuzumab therapy by improving ADCC.

-- "IL-21 enhancement of rituximab-mediated B cell depletion" Presenter: Steven D Hughes, Ph.D. Poster Number: G17 Abstract No: 2568. Conclusion: Treatment with IL-21 increased both lymphocytes and ADCC effector cells in circulation. Combined treatment with rituximab and IL-21 resulted in impressive depletion of B cells.

Abstracts

These abstracts will be available at www.zymogenetics.com in the "What's New" section on the home page.

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.

Forward-Looking Statements

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 ZymoGenetics' public filings with the Securities and Exchange Commission, including ZymoGenetics' Annual Report on Form 10-K for the year ended December 31, 2004. 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.

ZymoGenetics, Inc.
John Calhoun, 206-442-6744 (Investor Relations)
Susan W. Specht, 206-442-6592 (Media Relations)