Nuvelo today announced the formal presentation of clinical data from its Phase 1 alfimeprase trial in patients with chronic peripheral arterial occlusion (PAO), showing that alfimeprase was safe and well-tolerated with no drug related adverse events.

The Phase 1 data was presented today at the Advanced Interventional Management (AIM) Symposium in New York City. The presentation entitled, "Alfimeprase: A Novel New Thrombolytic Agent That May Reduce Complications And Improve Efficacy," was given by Dr. Jacob Cynamon, professor of clinical radiology and director, division of vascular and interventional radiology at the Montefiore Medical Center and a principal investigator for Nuvelo's Phase 2 alfimeprase trial for the potential treatment of PAO.

The presentation provided clinical data from Nuvelo's multi-center, open- label, dose-escalation Phase 1 study evaluating the safety and pharmacokinetics of alfimeprase in patients with chronic PAO. Each of the study's 20 patients was treated with one of five escalating weight-based doses of alfimeprase (0.025, 0.05, 0.1, 0.3, and 0.5 mg/kg), with four patients per dose group. Doses were delivered as manual, pulsed injections through a multi- sidehole infusion catheter. Angiograms were performed prior to treatment and one hour after administration of the drug.

There were no drug related serious adverse events observed. There were no immune responses observed, no signs of vascular wall damage noted and no aneurysmal changes were detected. In addition, plasminogen and fibrinogen levels remained unchanged, supporting the belief that alfimeprase acts directly, independent of the plasminogen-plasmin system and that the systemic inactivation of alfimeprase by alpha-2 macroglobulin appeared to be effective.

A dose-dependent consumption of alpha-2 macroglobulin was observed during administration of alfimeprase, consistent with the predicted binding of alfimeprase and subsequent clearance from the circulation.

Thrombolytic efficacy was not an objective of the study; however there were anecdotal observations of efficacy. One patient receiving 0.1 mg/kg experienced lysis of a clot approximately ten centimeters in length, approximately one hour after dosing. An additional four patients experienced partial thrombolysis.

"This early Phase 1 experience suggests that alfimeprase is well tolerated and has the potential to offer novel thrombolytic activity without some of the significant side-effects experienced today, such as major bleeding and intracerebral hemorrhage," said Dr. Cynamon. "Clinical trials are ongoing to confirm these findings."

Nuvelo previously announced the completion of this Phase 1 trial in March 2003 and rapidly initiated two Phase 2 alfimeprase trials in acute PAO and catheter occlusion in June 2003.

PAO affects more than 100,000 people annually in the U.S. alone and occurs when arterial blood flow is blocked to an extremity of the body by a clot. PAO usually occurs in the leg and is the result of underlying peripheral arterial disease (PAD), in which chronic fatty plaque buildup restricts blood flow. The classic early symptom of PAD is leg pain or fatigue during activity that subsides with rest. Acute PAO is due to an occlusive blood clot which results in the total blockage of flow. If blood flow is not restored, this can lead to ulcers, gangrene, tissue death and ultimately to foot or leg amputation.

Bypass surgery and angioplasty are established treatments for PAO; however treatment with thrombolytic drugs has presented a less-invasive and more cost- effective alternative. There are currently no approved, widely used products on the market to treat PAO. With the limited treatment options currently available, alfimeprase has received orphan drug designation for the PAO indication.

Alfimeprase is a modified fibrolase that directly degrades fibrin when delivered through a catheter at the site of a blood clot. Compared to traditional plasminogen activators, pre-clinical studies have shown alfimeprase to be up to six times faster in dissolving clots. In addition, alfimeprase's novel clearance mechanism appears to dramatically limit the molecule's half-life, reducing the risk of bleeding complications, a common side-effect of current therapies.

Alfimeprase was identified through Amgen's research program and partnered with Nuvelo in January 2002 for development and commercialization. Under the terms of the collaboration, Nuvelo will lead all clinical development activities and Amgen will be responsible for manufacturing activities. Amgen will have the option to lead the commercialization efforts in which both companies may participate.

The multi-center, open-label, dose-escalation Phase 2 study evaluating the safety and efficacy of alfimeprase in acute PAO patients is being led by Dr. Kenneth Ouriel, chairman of the division of surgery at the Cleveland Clinic, and Dr. Jacob Cynamon, professor of clinical radiology and director of the division of vascular and interventional radiology at the Montefiore Medical Center. The study is comparing three different doses of alfimeprase, in over 100 patients across twenty centers in the United States, Europe and South Africa.

Nuvelo is also currently conducting a Phase 2 trial to evaluate the safety and efficacy of alfimeprase in a second indication, catheter occlusion. This multi-center, randomized, double-blind study began in June 2003 and is comparing three doses of alfimeprase against the approved dose of t-PA (alteplase). Dr. Steven Deitcher, head of hematology and coagulation medicine at the Cleveland Clinic, is the principal investigator of the study that is being conducted in approximately 100 patients across twenty centers in the United States.

Nuvelo is engaged in the discovery, development and commercialization of life improving therapeutics for the treatment of human disease. Nuvelo's lead product candidate, alfimeprase, is partnered with Amgen and is currently in two Phase 2 trials in two indications, peripheral arterial occlusion and catheter occlusion.