Genta Inc. will collaborate with CV Therapeutics Inc. andStanford University researcher Victor Dzau to develop andcommercialize antisense drugs for preventing and treatingrestenosis, the San Diego company (NASDAQ:GNTA) announcedMonday.

Dzau, chief of the division of cardiovascular medicine atStanford University School of Medicine, will collaborate withGenta to investigate the mechanisms of restenosis and toidentify antisense compounds that may be useful in preventingor treating restenosis and other vascular conditions. "Stanfordhas already filed patent applications on some of thistechnology, which are the basis of our license from them,"explained Kenneth Brown, Genta's director of businessdevelopment.

Privately held CV Therapeutics (CVT) of Mountain View, Calif.,will work with Genta to develop such products. CVT is a co-licensee, along with Genta, to the exclusive worldwide rights ofthe Stanford antisense technology. Both companies will havethe right to market any products developed during thecollaboration and share income according to defined formulas.Genta will market and share income from any restenosisproducts through Genta/Jago, the joint venture it formed withthe Swiss company Jagotec AG in December 1992.

Genta will design, optimize and manufacture the antisensecompounds -- or Anticode, Genta's term for products in boththe antisense and triple strand areas -- while CVT will "finishsome of the preclinical research, correlate the toxicologystudies and supervise the clinical trials," said Louis Lange,CVT's chief executive officer. "We've already validated thetechnology in one animal model (of restenosis), and we'reready to go into another," Lange told BioWorld.

CVT plans to file an investigational new drug (IND) applicationin 1994, said Lange.

Restenosis, or the reclosing of arteries after coronaryangioplasty, is thought to be caused by the proliferation ofvascular smooth muscle cells in response to the injury inducedby the angioplasty procedure. The aim of the three-wayantisense collaboration is to develop antisense compounds thataffect the synthesis of the proteins that control cell division,particularly the proliferation of vascular smooth muscle cells.These therapeutic targets are not only "fundamental to cellgrowth," but in restenosis "the therapy is focal": It will bedelivered locally at the time of the angioplasty, Lange said.Moreover, he said, antisense therapy doesn't kill the cells, itjust prevents them from dividing.

No effective treatment to prevent restenosis currently exists.Other therapies under development include small moleculesthat affect calcium metabolism, anti-inflammatory agents suchas steroids, radiation and inhibitors of growth factors and theirreceptors, said Lange.

CV Therapeutics, which was founded in 1992 to developcardiovascular drugs via molecular cardiology, has received $6million in venture financing from Institutional VenturePartners, Delphi BioVentures, Asset Management Co., SequoiaCapital and Frazier & Co.

Genta, which raised $28.75 million in its initial public offeringin December 1991 (with shares priced at $10), last week pulledits follow-on offering of 2.5 million shares of common stock dueto market conditions. The company's stock (NASDAQ:GNTA)gained 25 cents Monday to close at $7.50 a share.

-- Jennifer Van Brunt Senior Editor

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