ZymoGenetics Reports New Findings on Anti-thrombotic Activities of CTRP1; Novel Protein Prevents Platelet Thrombosis without Causing Bleeding.

Business Editors/Health/Medical Writers

SEATTLE--(BUSINESS WIRE)--July 17, 2003

ZymoGenetics (Nasdaq:ZGEN) reported today that CTRP1, a protein discovered through its bioinformatics-driven discovery efforts, has potent anti-thrombotic activities while not causing adverse bleeding events. These findings were described at the International Society on Thrombosis and Haemostasis (ISTH) Congress that is being held in Birmingham, UK. CTRP1, also known as zsig37, may provide a novel mechanism of action for the prevention and treatment of thrombotic complications associated with various types of vascular injuries, while minimizing the potential for bleeding complications.

"CTRP1 is a potent local acting anti-thrombotic yet appears to lack any systemic effect on blood coagulation, reducing concerns for bleeding complications associated with its use," stated Frank Collins, Ph.D., Senior Vice President and Chief Scientific Officer of ZymoGenetics. "The combination of locally acting anti-thrombotic efficacy with a favorable safety profile suggests that CTRP1 may have therapeutic potential in a variety of settings."

In the preclinical studies reported at the ISTH meeting, CTRP1 was shown to be effective in preventing clot formation in several animal models of vascular injury. These included inhibiting a platelet-rich blood clot and maintaining blood flow in injured carotid arteries of non-human primates and in a rabbit model of balloon angioplasty that mimics a common treatment for coronary artery disease. A single dose of CTRP1 was found to yield a therapeutic effect lasting more than 24 hours.

CTRP1 (C1q-TNF Related Protein-1) works by binding to collagen exposed at the site of an injured blood vessel and preventing platelet activation and aggregation by interfering with the interaction between platelets and the exposed collagen. Platelets are cells found in the blood that are involved in the formation of blood clots. While platelet-rich clot formation is required to stop bleeding, especially in settings involving tissue repair, inappropriate clot formation can lead to a complete blockage of the injured blood vessel. In situations where surgical interventions are used to treat partially or completely blocked coronary arteries, such as balloon angioplasty or the placement of stents, the procedure itself causes injury to the lining of the treated artery. This injury can initiate blood clot formation at the site of treatment, leading to the establishment of an occlusive clot at the treatment site and the development of a heart attack. Current therapies for preventing acute clot formation include platelet inhibitors such as IIb/IIIa antagonists, and inhibitors of specific blood coagulation factors, such as thrombin.

While current therapies such as the IIb/IIIa antagonists are effective at preventing platelet-rich clot formation, their use is limited due to the fact that the ability to control bleeding is inhibited systemically, thereby increasing the risk of adverse bleeding events in patients. Preclinical studies with CTRP1 have demonstrated that it does not prolong bleeding times when tested in animals, including non-human primates and rabbits. By not affecting bleeding times CTRP1 may be useful in a number of indications where bleeding is of major concern, such as neurosurgery.

About CTRP1

CTRP1, also known as zsig37 and C1QTNF1, is a member of the C1q-TNF family of proteins. The protein contains a collagen-like domain at one end of the protein and a TNF-like globular domain at the other end. The basic structural unit of CTRP1 is a homo-trimer that is held together by disulfide bonds and non-covalent interactions. CTRP1 is expressed in a variety of tissues including endothelial and vascular smooth muscle cells present in blood vessels.

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 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, including preclinical and clinical development activities for zsig37, 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.