SUNNYVALE, Calif., Aug. 8 /PRNewswire-FirstCall/ -- Nuvelo Inc., (NASDAQ: NUVO) today announced the publication of clinical data from the Phase 1 trial of its lead product candidate, alfimeprase, in the August issue of the Journal of Vascular and Interventional Radiology. The study of patients with chronic peripheral arterial occlusion (PAO) showed that alfimeprase was generally well-tolerated with no bleeding complications. "Plasminogen activators, which are currently used to treat acute PAO, can take several hours to days to work and can cause significant side effects, including bleeding and intracerebral hemorrhage," said Kenneth Ouriel, M.D., Chairman of the Division of Surgery at The Cleveland Clinic and a lead investigator for Nuvelo's alfimeprase PAO trials. "A drug with the ability to localize its lytic activity to the target blood clot within a notably decreased treatment time would represent a significant advance in treatment for this very sick patient population." The Phase 1 multicenter, open-label, dose-escalating study evaluated the safety and pharmacokinetic profile of alfimeprase in patients with chronic lower extremity PAO. Each of the study's 20 patients was given one of five escalating doses of intra-arterial alfimeprase (0.025, 0.05, 0.1, 0.3 and 0.5 mg/kg). Results showed that no drug-related serious adverse events were observed. Plasminogen and fibrinogen levels remained unchanged, further evidence that alfimeprase acts directly, independent of the plasminogen-plasmin system. There was a dose-dependent consumption of alpha-2 macroglobulin, the protein that rapidly inactivates alfimeprase once it enters the systemic circulation. Alpha-2 macroglobulin levels returned to baseline within 14 days of receiving drug. In addition, no anti-alfimeprase antibodies were detected within 3 months after drug exposure. Since this Phase 1 study was conducted in chronic PAO patients, thrombolytic efficacy was not an objective of the study, however, lysis of blood clots and restoration of blood flow were observed in 40% of cases. "The safety findings in this Phase 1 trial have since been confirmed in a Phase 2 study, and our Phase 3 program is now underway to evaluate the efficacy of alfimeprase in patients with acute PAO," said Michael D. Levy, M.D., senior vice president, research and development for Nuvelo. "Clinical trials to date have demonstrated that alfimeprase is well tolerated and has shown potential as a rapid-acting clot dissolver with a favorable safety profile and attractive dosing schedule." About Acute PAO Acute peripheral arterial occlusion (PAO), or "leg attack," is the blocking of arterial blood flow to the lower limbs by a clot. Affecting more than 100,000 people in the United States per year, it is the result of underlying peripheral arterial disease, in which chronic fatty plaque buildup restricts blood flow and is then complicated by the formation of an acute clot. If blood flow is not restored quickly, leg attack can lead to permanent nerve and muscle damage, gangrene, and in the most severe cases, amputation and death. Because there is no FDA approved thrombolytic therapy available to treat acute PAO, plasminogen activators are often used off-label in this indication. About Alfimeprase Alfimeprase, an enzyme produced by recombinant DNA technology, is a thrombolytic or blood clot dissolver that possesses a unique mechanism of action. It has the ability to directly degrade fibrin, producing a rapid dissolution of blood clots. In clinical studies, alfimeprase has been shown to degrade large arterial clots within four hours of initiation of dosing as well as the ability to restore function to occluded catheters in as early as five minutes. Thrombolytics currently on the market such as Activase(R) are plasminogen activators which rely on the plasminogen system to degrade fibrin. The activity of plasminogen activators is impacted by the amount of plasminogen found in the blood clot and according to published studies, may require prolonged infusions averaging 24 to 36 hours when dissolving very large clots such as those found in patients with acute PAO. In addition, preliminary testing suggests that alfimeprase's lytic activity is localized to the site of delivery because within seconds of moving away from the clot and into the general circulation, it is inhibited by alpha-2 macroglobulin, a naturally occurring protein in our blood. This clearance mechanism helps focus the thrombolytic activity to the site of delivery and, in clinical testing, appears to minimize bleeding side effects. In contrast, studies have shown that plasminogen activators can cause major bleeding in 5-16% of patients and intracerebral hemorrhage (ICH) in 1-2% of patients. Alfimeprase in Clinical Trials A Phase 3 trial of alfimeprase for the treatment of acute PAO is currently ongoing. This randomized, double-blind study is comparing 0.3 mg/kg of alfimeprase versus placebo in 300 patients at more than 100 centers worldwide. It is the first of two overlapping Phase 3 trials evaluating alfimeprase for the treatment of acute PAO. The Phase 3 acute PAO program is expected to include up to 700 patients between the two trials. The second Phase 3 trial is expected to begin in the second half of 2005. A separate Phase 3 clinical program for alfimeprase in catheter occlusion is expected to begin enrollment in the second half of 2005. This program will include two overlapping, multi-national trials. The first trial is an efficacy study comparing 3 mg of alfimeprase versus placebo in 300 patients with occluded central venous catheters, evaluating restoration of function to the catheters at 15 minutes. The second trial will be an open-label, single-arm trial evaluating alfimeprase alone in 800 patients. This study's primary endpoint is safety, however efficacy will also be evaluated. About Nuvelo Nuvelo, Inc. is engaged in the discovery, development and commercialization of life improving therapeutics for the treatment of human disease. Nuvelo's clinical pipeline includes three product candidates, alfimeprase, a direct acting thrombolytic for the treatment of acute peripheral arterial occlusion (PAO) and catheter occlusion; rNAPc2, an anticoagulant that inhibits factor VIIa/tissue factor; and ARC183, a direct thrombin inhibitor that is being developed for use in acute anticoagulant applications. Nuvelo recently identified NU206 as a preclinical development candidate from its proprietary research programs and expects to leverage expertise in secreted proteins and antibody discovery to expand its pipeline and create partnering and licensing opportunities. Information about Nuvelo is available at our website at http://www.nuvelo.com/ or by phoning 408-215-4000. This press release contains "forward-looking statements" regarding potential use of alfimeprase as a treatment for PAO and catheter occlusion and timing and progress of Nuvelo's clinical stage and internal research programs, which statements are hereby identified as "forward-looking statements" for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. Such statements are based on our management's current expectations and involve risks and uncertainties. Actual results and performance could differ materially from those projected in the forward looking statements as a result of many factors, including, without limitation, uncertainties relating to drug discovery; clinical development processes; enrollment rates for patients in our clinical trials; changes in relationships with strategic partners and dependence upon strategic partners for the performance of critical activities under collaborative agreements; the impact of competitive products and technological changes; uncertainties relating to patent protection and uncertainties relating to our ability to obtain funding. These and other factors are identified and described in more detail in Nuvelo filings with the SEC, including without limitation Nuvelo's recent annual report on Form 10-K for the year ended December 31, 2004 and subsequent filings. We disclaim any intent or obligation to update these forward-looking statements. DATASOURCE: Nuvelo Inc. CONTACT: Nicole Estrin, Associate Director of Corporate Communications & IR of Nuvelo Inc., +1-408-215-4572, or ; or Carolyn Bumgardner Wang of WeissComm Partners, Inc., +1-415-946-1065, or , for Nuvelo Inc. Web site: http://www.nuvelo.com/

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