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ZymoGenetics Demonstrates Anti-tumor Activity with Interleukin-21.

Business Editors/Health/Medical Writers


Activation of Cytotoxic T-cells and Natural Killer Cells May Enhance

the Body's Ability to Defend Itself against Cancer

ZymoGenetics (Nasdaq:ZGEN) reported at the American Association of Cancer Research (AACR) meeting in Washington D.C. that Interleukin 21 (IL-21) treatment suppressed the growth of the tumors in mice without the toxic effects commonly seen with other cytokine therapies. In a mouse model of melanoma, an aggressive form of skin cancer for which there are limited therapeutic treatments, IL-21 was able to significantly decrease the number of metastases that formed in the lungs of the animals. IL-21, a protein discovered through ZymoGenetics' genomic research efforts, stimulates the proliferation and activation of natural killer cells and cytotoxic T cells, cell types involved in the destruction of cancerous and infected cells.

"This is another example of our ability to identify novel protein therapeutics from our bioinformatics-driven research efforts, identify the relevant biological activities of the protein and confirm the therapeutic potential of the protein in animal models of disease," commented Bruce L. A. Carter, Ph.D., president and chief executive officer of ZymoGenetics. "IL-21 is the second protein coming from our genomics platform that we have targeted for development, with a number of others advancing through preclinical studies that could address a variety of indications."

The mouse model described in the AACR presentation consisted of injecting mice with mouse melanoma cells. The mice were treated with murine IL-21, starting either the day of tumor cell injection or four days later. Eighteen days following the injection of the tumor cells, the mice were sacrificed and the number of metastases on the lungs counted. Compared to untreated animals, IL-21 treatment caused a significant decrease in the number of lung metastases, regardless of whether treatment was started on the day of tumor cell injection or delayed.

IL-21 is closely related to other cytokines with proven medical utility, including Interleukin 2 (IL-2). One of the limiting factors for IL-2 therapy for human cancer is the toxic side effects that are associated with its use. Interleukin-21 was well tolerated by the mice and did not cause the "vascular leak" syndrome commonly associated with IL-2 therapy. Addressing this issue, ZymoGenetics reported results from a direct comparison between murine IL-21 and human IL-2 for potential toxic side effects in mice.

Vascular leak syndrome, the leakage of fluids into the lungs which is associated with decreased lung function, was significantly lower in the IL-21 treated mice than was observed for the mice treated with IL-2 at the same dose. A significant increase in the presence of inflammatory cytokines, including TNF-alpha, which is thought to play a key role in acute inflammatory reactions, was observed in the serum of mice treated with IL-2, while no increase was seen with IL-21 treatment. Examination of lung tissue of IL-2 and IL-21 treated mice demonstrated significantly elevated levels of inflammatory cells in the IL-2 treated mice as compared to mice treated with IL-21.

"The data presented at the AACR meeting demonstrates that IL-21 has significant anti-tumor activity in animal models without the toxic responses that currently limit the use of IL-2 as an anti-cancer agent," stated Jan K. Ohrstrom, M.D., senior vice president and chief medical officer of ZymoGenetics. "We are aggressively moving forward with IL-21 and intend to file an IND and initiate clinical studies in the first half of 2004. We plan to initially target metastatic melanoma and renal cell carcinoma. However, because of the mechanism of action through which IL-21 appears to work, we believe that it has the potential to be an effective therapy against a large number of cancer types, both as a stand alone compound and as adjuvant therapy to current cancer treatments."

The Company is collaborating with Novo Nordisk A/S in the development of IL-21. ZymoGenetics has retained all commercial rights to IL-21 within North America, while Novo Nordisk maintains commercial rights in the rest of the world. The two companies have agreed to collaborate and share costs on all research and development activities leading up to the filing of an Investigational New Drug application (IND).

IL-21 Background

IL-21 is a member of the four-helix bundle cytokine family of secreted proteins and is most closely related by amino acid sequence homology to IL-2 and IL-15. The four-helix bundle cytokine family includes many of the most significant therapeutic proteins developed to date, including erythropoietin, granulocyte colony stimulating factor, granulocyte-macrophage colony stimulating factor, growth hormone, interferon alpha and interferon beta. While these proteins share a common secondary and tertiary structure, the biological properties associated with the members of this family are extremely varied. This has led to their clinical use across a diverse set of therapeutic areas.

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, comprising genomics, bioinformatics, protein chemistry and preclinical biology, ZymoGenetics has generated a broad pipeline of proprietary product candidates. ZymoGenetics intends to commercialize these product candidates through internal development, collaborations with biopharmaceutical partners, and out-licensing of its extensive patent portfolio. For further information, visit

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, including preclinical and clinical development activities for Interleukin 21, 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 Dec. 31, 2002.
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Publication:Business Wire
Date:Jul 14, 2003
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