Agouron Pharmaceuticals Inc. said Wednesday that it is initiating aPhase II program for its drug AG337 that will test the agent againstsolid malignant tumors of the colon, lung, liver, pancreas, prostateand head and neck.Fourteen evaluable patients with limited exposure to anti-cancerdrugs will be enrolled for each of the six tumor types. Additionalpatients will be accrued for any of the tumor types in which aresponse is seen."We know the drug is active," Peter Johnson, Agouron's presidentand CEO, told BioWorld. "The question is how active and againstwhat disease? That's what we'll be determining in Phase II."Johnson said evidence of anti-cancer activity was seen in Phase Itrials, which also determined the safety profile of the drug and theappropriate Phase II dose for five-day intravenous infusion. Thedrug currently is being developed as a single therapy.AG337 is a small synthetic molecule designed to inhibitthymidylate synthase, an enzyme needed for sustained proliferationof cancer cells. Blocking thymidylate synthase produces an anti-proliferative effect selective for cancer cells, Johnson said.Donna Nichols, director, corporate communications for the La Jolla,Calif., company, explained the trial methodology further: "If one ormore responses are observed in the first 14 evaluable patients in anytumor type, then 11 to 16 additional patients will be enrolled topermit for a true response rate of that tumor type to AG337."A partial response, Nichols told BioWorld, is a reduction of tumorsize by more than 50 percent that endures for more than four weeks.The complete elimination of a tumor for four weeks is a completeresponse.A Phase I trial of an oral formulation of AG337 is ongoing at theUniversity of Newcastle upon Tyne in England, where Phase Istudies of the molecule delivered intravenously also wereconducted.AG331, another inhibitor of thymidylate synthase but with adifferent structure and properties than AG337, is in Phase I trials inthe U.S. Agouron holds all rights to both AG331 and AG337, itslead product.Neil Clendeninn, Agouron's vice president, clinical affairs, saidPhase I studies of AG337 showed it to well tolerated as achemotherapeutic agent. "The dose-limiting toxicities proved to beamong those expected for an anti-proliferative agent:myelosuppression, which was of short duration; and mucositis,which could be mitigated by simple measures," he said in a newsrelease.Phase I details will be presented at a scientific meeting in the nearfuture, Clendeninn said.Separately, Agouron has an HIV protease inhibitor, AG1343, that ithopes to have in Phase I trials by the end of the year, Nichols said.Agouron acquired the non-peptidic protease inhibitor from Eli Lillyand Co. in exchange for proprietary details of the three-dimensionalstructure of an undisclosed enzyme.Agouron is working with Japan Tobacco Inc. on developing drugsthat inactivate protease enzymes, in the areas ofimmunosuppression and certain anti-virals. The deal potentially isworth $57 million to Agouron.Another collaboration, worth up to $12 million, is with SyntexCorp. for discovery of novel drugs for treating arthritis and certainmalignant tumors, based on the design and development of selectiveinhibitors of matrix metalloproteases.Syntex would get rights to any arthritis drugs, and pay Agouronroyalties. Agouron would get rights to any cancer drugs and payroyalties to Syntex. Nichols said a development candidate likelywill be named in six to 12 months.Agouron stock (NASDAQ:AGPH) was up 13 cents Wednesday,closing at $11.38 per share. n

-- Jim Shrine

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