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Fred Hutchinson Researchers Present Preliminary Clinical Results with Antibody to Treat Severe Graft Versus Host Disease

Researchers from the Fred Hutchinson Cancer Research Center (FHCRC) will present preliminary results from a phase I clinical trial showing that Nuvion™ (HuM291) was an effective therapy in some marrow transplant patients with severe graft versus host disease (GVHD). The data will be presented at the 42nd annual meeting of the American Society of Hematology in San Francisco.

The research team led by Dr. Paul Carpenter of the Hutchinson Center designed the trial to assess the safety, tolerability and optimal dose of the Nuvion antibody in bone marrow transplant patients who developed severe (grade III-IV) acute GVHD and were not responsive to conventional therapy. Fifteen patients whose GVHD was resistant to prednisone and other immunosuppressive drugs received either a single dose or seven doses of Nuvion. No immediate severe toxicities or other allergic or inflammatory responses were observed.

"Although there has been some progress in the prevention of acute GVHD over the past two decades, little progress has been made in the treatment of acute GVHD. Despite best available preventive strategies, GVHD remains the primary life-threatening complication for our patients," says Dr. Carpenter. "Early testing of Nuvion has indicated that the antibody is well tolerated and that complete responses can be achieved in patients who have the most severe forms of GVHD."

Manifestations of GVHD, which can includes severe skin blistering, diarrhea and jaundice, among other conditions, improved in all of the patients. Complete resolution of GVHD was observed in six of the nine patients who received a single Nuvion dose. The other three single-dose patients had partial responses, as did all six of the patients who received multiple doses of Nuvion.

"While this clinical research is still in its early stages, we are encouraged by the preliminary efficacy seen with Nuvion to date," says Dr. Claudio Anasetti, member of the clinical research division at FHCRC. "Few, if any, treatment alternatives are available for these patients with severe GVHD, so it has been encouraging to see clinical responses in our initial testing."

Nuvion is a humanized anti-CD3 antibody that targets T lymphocytes, the cell type involved in GVHD. Protein Design Labs, Inc., which humanized Nuvion, also engineered the antibody tail to avoid the toxicity from cytokine release that occurs with other anti-CD3 antibodies.

Fred Hutchinson Cancer Research Center is an independent, nonprofit research institution dedicated to the development and advancement of biomedical technology to eliminate cancer and other potentially fatal diseases. Recognized internationally for its pioneering work in bone-marrow transplantation, the Center's four scientific divisions collaborate to form a unique environment for conducting basic and applied science. The Hutchinson Center is the only National Cancer Institute-designated comprehensive cancer center in the Pacific Northwest. For more information, visit the Center's Web site at <www.fhcrc.org>.

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Editor's Note: Dr. Carpenter will present these results in the Clinical Bone Marrow Transplantation: Acute GVHD session in room 305 at 8:45 a.m. on Monday, Dec. 4.

In a related development, Drs. Carpenter, Anasetti and colleagues at FHCRC and Protein Design Labs, Inc., published research concerning the mechanism of action of Nuvion in the December 1, 2000 issue of the Journal of Immunology. Their study indicates that the humanization of Nuvion and other modifications to the constant region of the antibody result in the selective death, or apoptosis, of activated T cells. These results predict that Nuvion might be able to induce a state of immunological tolerance by selective depletion of activated T cells.

CONTACT: Susan Edmonds
sedmonds@fhcrc.org
(206) 667-2896

Mark Gaspar
GCI Health Technology
415-356-9627
mgaspar@gcigroup.com

EMBARGOED FOR RELEASE
Dec. 4, 2000, 8AM PST

Fred Hutchinson Cancer Research Center is a world leader in research to prevent, detect and treat cancer and other life-threatening diseases.