Nancy GarciaAssociate Editor

Repligen Corp. filed an investigational new drug (IND)application with FDA to begin Phase I studies of an antibody tofight acute inflammation.

Clinical trials are scheduled at the University of Michigan inpatients with chronic pulmonary inflammation to establishsafety of the compound, a monoclonal antibody. The antibodyadheres to the CD11b surface protein of neutrophils, blockingmovement of these white blood cells to tissues and haltingrelease of destructive substances.

Acute inflammation causes life-threatening tissue damage. Itresults from many conditions, such as multiple trauma,myocardial infarction and sepsis. About 900,000 patientsdevelop these three conditions in the U.S. each year. Thecompany plans to pursue transplantation in addition to thesethree indications for treatment with a hospital-basedintravenous therapy for use in life-threatening situationswhere a single, quick preventive is required.

"Repligen and Eli Lilly and Co., our collaborator in testing anddeveloping the antibody to CD11b, believe we are pursuing aparticularly promising approach to preventing inflammation-induced tissue damage," said Sandford D. Smith, president andchief executive officer of the Cambridge, Mass., company(NASDAQ:RGEN).

"In addition, we believe Repligen and Lilly are the first toconduct human studies utilizing an anti-integrin antibodyapproach," he said.

The compound targets the Mac-1 integrin, one of two integrinsthat allow neutrophils to move from blood vessels intosurrounding tissue. The Mac-1 also is responsible for adherent-dependent release of tissue-damaging substances.

Repligen focused on CD11b and Mac-1 in 1991 as beingpotentially promising because the trafficking of neutrophils totissue is common to a variety of inflammation pathways.

Biogen Inc. (NASDAQ:BGEN), also of Cambridge, is alsoinvestigating ways to block neutrophils from migrating intoinflamed tissue, while Genentech Inc. (NASDAQ:GNE) of SouthSan Francisco, Calif., is exploring the role of adhesion moleculesin inflammation in a five-year, $20-million agreement withXenova Ltd. of Slough, England.

"Lilly took a look at different approaches before they chose us,"Ramesh L. Ratan, Repligen's senior vice president and chieffinancial officer, told BioWorld. "Lilly made a decision thatRepligen's approach makes the most sense based on the dataavailable."

Repligen licensed a broad-use patent in January 1991 from theUniversity of Michigan covering CD11b antibodies, then inOctober 1991 obtained exclusive rights from Kabi PharmaciaAB to antibodies that bind both the CD11b and CD18 neutrophilintegrins.

Anti-CD11b antibodies have been shown in various preclinicalstudies to prevent or reduce injury to heart, lung and livertissue.

Trials may begin in one month after the FDA has had 30 daysto respond with any questions. A product could reach marketin four to five years if the development process continues ontrack.

(c) 1997 American Health Consultants. All rights reserved.

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