The first antisense anticancer compound from the IsisPharmaceuticals Inc./Ciba-Geigy Ltd. collaboration started in 1990 isgoing into the clinic, and another one is following soon.
The compound, ISIS 3521, selectively inhibits protein kinase C-alphagene expression. It inhibited growth of several solid tumor types innude mouse xenograft models at doses far below toxic levels, Isissaid.
Isis executives, speaking on a conference call with reporters, saidthey're normally not much for touting drugs before their utility hasbeen demonstrated in humans. But they made an exception for ISIS3521 and, and another compound, ISIS 5132, which will be takeninto the clinic shortly.
Officials said the outstanding results they've seen in animal data canbe explained only by saying that the antisense mechanism isresponsible. Antisense drugs are designed to bind to the receptorsequence on messenger RNA that codes for a specific protein and tointerfere with production of that protein.
The Phase I studies at the Cancer Therapy and Research Center inSan Antonio will be in cancer patients, so some efficacy data will beavailable. The plan is to take the drug from there as a single agentinto tumor-specific Phase II trials, and at that time start studies inEurope.
Stanley Crooke, chairman and CEO of Carlsbad, Calif.-based Isis,said the multi-gene protein kinase C (PKC) family has been a focusof Isis drug discovery efforts for years. A key problem, he said, hasbeen developing isotype-selective drugs.
The company identified 13 members of the family, developedinhibitors to all the major isotypes, and selected PKC-alpha, sayingits inhibition was associated with important anticancer activity.
Dan Kisner, president and chief operating officer at Isis, said, "Weare very excited about the high level of activity demonstrated by ISIS3521 . . . with its low potential for toxicity. Even in this early stage ofdevelopment, the profile of this anticancer compound looks veryattractive."
The other compound, ISIS 5132, also is being developed with Basel,Switzerland-based Ciba, and targets another multi-gene familyinvolved in cancer growth. The collaboration incorporating bothdrugs could be worth $100 million to Isis. (See BioWorld Today,Sept. 18, 1995, p. 1.) n
-- Jim Shrine
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