Cortech Inc.'s partner, Marion Merrell Dow (MMD), isbroadening a development agreement for a potential lungdisease treatment in a program that is expected to bring theyoung biopharmaceutical company "well above" $10 million infunding.

Cortech of Denver has been developing drugs to inhibit thebreakdown of connective tissue in the lung, with funding fromMMD since 1987, said David Crossen, Cortech's president andchief executive officer.

The lead neutrophil elastase inhibitor, a synthetic ester thataddresses needs for solubility and specificity, will now beexplored for use in cystic fibrosis and a congenital emphysemaresulting from lack of the protective enzyme alpha 1 Pi, as wellas in adult respiratory distress syndrome (ARDS).

An investigative new drug (IND) application for ARDS isexpected by the end of the year, while the two additionalindications, which require an aerosol form of the drug, could beready for IND applications in 1994.

A common outcome of systemic inflammatory responseresulting from massive burns, blood infection or widespreadwounds, ARDS has a fatality rate of 50 to 70 percent, andwould be treated through peritoneal injection, said Crossen.

Cystic fibrosis, which often causes the development ofinfections with thick mucus secretions in the lungs, affectsabout 60,000 Americans. Congenital emphysema occurs inabout 10,000 Americans, but if the drug appears promising, itwould be tested in the larger market of chronic emphysema.

Cortech, with funding from MMD, is managing preclinical andclinical development of the lead compound, CE-1037. Accordingto Crossen, Cortech has looked at many different species foranimal testing, and determined that human elastase is verydifferent. So preclinical testing has examined the compound'sability to prevent degradation of extracellular matrix in vitroand its bioavailability in animals that do not mimic humandisease.

MMD holds an exclusive, royalty-bearing license on all productscovered by an allowed U.S. patent application that includes CE-1037. The corporate partner will also receive any royaltiesresulting from products that might be developed by Cortech ora licensee based on two additional allowed patents.

MMD also holds a right of first negotiation on productsresulting from these two patent applications other than usesfor skin, gum or eye diseases. Cortech is especially interested indeveloping skin treatments for wounds, psoriasis or contactdermatitis in a second-generation product that combines anelastase inhibitor with a bradykinin inhibitor which blocks theinflammatory response leading to release of elastase.

CE-1037 is complementary to the bradykinin approach in ARDSand the other lung indications, too, Crossen added. Cortechresearchers are searching for orally active compounds, whichwould be suitable for use in chronic emphysema and in the"holy grail" of rheumatoid arthritis, in which elastase damagessmooth tissue in the joints.

The small compound CE-1037 is active in the bloodstream,where endothelial cells lining the blood vessels bind circulatingneutrophils. The neutrophils release elastase and migrate tothe site of injury or infection, causing tissue destruction andorgan damage if they are present in excess.

MMD entered equity agreements in 1988 and 1990 withCortech (NASDAQ:CRTQ), which went public in November 1992.MMD (NYSE:MKC) of Kansas City, Mo., is Cortech's first and onlycorporate partner.

-- Nancy Garcia Associate Editor

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

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