PRESS RELEASE: ZymoGenetics Presents Positive Interim Phase 1 Results for IL-21

ZymoGenetics Presents Positive Interim Phase 1 Results for IL-21 in Combination with Rituxan® in B Cell Lymphoma

Good Safety Profile and Anti-Lymphoma Activity Observed

SEATTLE -- ZymoGenetics today presented interim results from a Phase 1 clinical trial of Interleukin 21 (IL-21) in combination with Rituxan® (rituximab) in patients with relapsed low-grade B Cell lymphoma at the American Society of Hematology (ASH) 2007 Annual Meeting. The Phase 1 study is part of a larger clinical program examining the use of IL-21 both as a single agent and in combination with approved cancer therapeutics.

“The Phase 1 data show that the combination of IL-21 with rituximab was well tolerated and resulted in anti-lymphoma activity,” said Nicole Onetto, M.D., Senior Vice President and Chief Medical Officer of ZymoGenetics. “IL-21 may increase the ability of approved therapies like rituximab to target and kill cancer cells.”

The ASH poster presentation, “Recombinant Interleukin-21 Plus Rituximab: Clinical Activity in a Phase 1, Dose-Finding Trial in Relapsed Low-Grade B Cell Lymphoma,” reviewed results from 15 subjects from the two-part open label multi-center study. Part 1 of the study included 9 patients and consisted of dose-escalation portion to identify a dose of IL-21 that can be safely combined with rituximab. Part 2 of the study is evaluating the safety and anti-tumor effects of the combination in an expanded cohort of 12 additional patients to be treated at the dose identified in Part 1. Results from 6 subjects in Part 2 were reported at ASH.

The study evaluated three dose levels of IL-21 (30, 100 and 150 mcg/kg), given intravenously once per week in combination with a standard dose of rituximab (375 mg/m2) for four weeks. While no dose limiting toxicities were seen at any dose level, a dose of 100 mcg/kg of IL-21 in combination with rituximab was selected for cohort expansion as re-treatment at 150 mcg/kg was associated with increased toxicity. The majority of adverse events and lab abnormalities at all dose levels were Grade 1 or 2 and included flu-like symptoms, headache, fatigue and nausea. One subject with a prior history of cardiac disease who experienced chest pain during the study died of complications after a stenting procedure and was not evaluable for response. Evidence of anti-tumor activity was seen in this heavily pretreated group of patients, most of whom had previously received rituximab. Best response during the study, per investigator assessment, included 2 complete responses, 4 partial responses, 7 stable disease and 1 progressive disease. Final data from the study will provide more information about the overall safety and anti-tumor effects of this combination therapy.

Previous IL-21 studies

Previous clinical studies with IL-21 alone have shown that IL-21 is an active cytokine that can be administered in an outpatient regimen. Results from a Phase 1 study presented at the American Society of Clinical Oncology (ASCO) 2006 annual meeting showed that IL-21 administration was tolerable in an outpatient setting and reductions in tumor size were observed in several patients. Interim results from a Phase 1 trial of IL-21 in combination with Nexavar® in patients with renal cell cancer were presented in October 2007 at the AACR-NCI-EORTC International Conference. The preliminary data indicated that the combination of IL-21 and Nexavar is well tolerated, with a toxicity profile similar to known toxicities of each agent alone. Preliminary evidence of anti-tumor activity was also documented in the majority of the patients treated in Phase 1. Available clinical data support further clinical investigation of IL-21 as a new therapeutic agent for the treatment of cancer.

About IL-21

Endogenous IL-21 has potent biological activity in regulating key classes of immune cells, including cytotoxic T cells and natural killer cells. These cell types play important roles in eliminating malignant and infected cells. Based upon the ability of IL-21 to inhibit tumor growth in a number of animal models, ZymoGenetics is developing a recombinant form of IL-21 for the treatment of cancer, initially in metastatic melanoma and renal cell carcinoma and has retained commercialization rights for IL-21 in North America. The company licensed commercialization rights outside of North America to Novo Nordisk A/S.

Recombinant Thrombin (rThrombin) ASH poster

In addition, an encore presentation reviewing immunogenicity data from the recombinant Thrombin (rThrombin) Phase 3 clinical study was given at the ASH meeting. The Phase 3 pivotal clinical trial showed that rThrombin had comparable efficacy and significantly lower immunogenicity compared to the commercially available bovine thrombin product. Adverse events were reported with similar frequency in the two treatment groups (rThrombin or bovine thrombin).

About ZymoGenetics

ZymoGenetics creates novel protein drugs with the potential to significantly help patients fight their diseases. The company is developing a diverse pipeline of product candidates that are moving into and through clinical development. These candidates span a wide array of clinical opportunities that include bleeding, autoimmune and viral 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

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, 2006. 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.