Nova Pharmaceutical Corp. has developed a second generationof its bradykinin antagonists that is 600-800 times morepotent than its first agent and promises to lead to an evenbetter third generation of anti-inflammatory compounds.

Scientists for years have attempted to treat pain andinflammation by blocking the action of proteins called kininsas an alternate to steroids and prostaglandins. But untilrecently, a long-acting, clinically useful kinin blocker haseluded discovery.

Hoechst A.G. of Frankfurt, Germany, had beaten the smallerNova to publish on a new kinin antagonist class. But with itspublication Monday in the Journal of Medicinal Chemistry, Novais clearly not out of the running.

"I suspect Hoechst is further ahead than we are," Hans Mueller,Nova president and chief executive officer, told BioWorld.Bradykinin antagonists offer "a promising field of attack,"with obvious reasons for competition, Mueller said.

The company's first bradykinin blocker, NPC 567, is in PhaseI/II clinical studies, which Nova expects to complete by year'send.

The new antagonists, in addition to having greater potencythan NPC 567, last up to four hours in the body. "The Hoechstcompound is in that same ballpark," said Mueller.

The new blockers work in animal models of severalinflammation-based diseases, including asthma and septicshock, Mueller said. Yet the drugs would only work byinjection, by inhalation or by topical application.

The company is investigating a third set of blockers thatwould work orally now that Nova scientists have informationon the required structure for kinin action.

"Nova's ultimate aim," Muller said, "is to find non-peptideanalogs" of bradykinin, to allow oral delivery of the potentialpain killers.

New knowledge of kinin structure is detailed in Monday'sjournal article, which describes studies using the secondgeneration of peptide antagonists, built with altered aminoacids that do not occur in nature. Nova scientists used ethersof hydroxyproline to construct the new, potent kinin blockers.

Nova expects to file investigational new drug applications onthese constrained peptide analogs by the latter portion of nextyear, Mueller said, in order to test the drugs clinically.

Stock of the Baltimore-based company (NASDAQ:NOVX) closedat $4.50 on Tuesday, up 25 cents.

-- Roberta Friedman, Ph.D. Special to BioWorld

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