Isis Pharmaceuticals Inc. said Wednesday it received a$28.5 million equity investment from BoehringerIngelheim International GmbH as the companies signed adefinitive agreement to collaborate in the area of celladhesion, as announced on March 1.

The equity investment, part of a potential $100 milliondeal, was made at $15 per share, more than twice theprice the stock was trading at when the letter of intentwas announced. (See BioWorld Today, March 2, p. 1.)The premium paid does not seem as large now, as Isis'stock (NASDAQ:ISIP) closed Wednesday at $12.38, up38 cents.

Germany-based Boehringer Ingelheim's stake in Isis isabout 8 percent with the purchase of the 1.9 millionshares. Isis, of Carlsbad, Calif., reported having about19.8 million shares outstanding on March 31.

Isis' lead compound as it relates to the collaboration isISIS 2302, an antisense oligonucleotide designed toinhibit intercellular adhesion molecule 1 (ICAM-1). Thecompany is in the final stages of planning pilot Phase IItrials of the compound in five areas: rheumatoid arthritis,psoriasis, ulcerative colitis, Crohn's disease and organtransplant rejection. Future development plans will bebetter defined after the series of trials, said Jane Green,Isis' director of investor relations and corporatecommunications.

Isis will have access to a $40 million line of credit fromBoehringer Ingelheim, and will get royalties onworldwide sales of BIRR1, a murine monoclonalantibody-based product in Phase II and III trials in threeindications. Additionally, the privately held Germancompany will make additional equity investments in Isis,at a premium, for attainment of various milestones.

In a separate matter, Green said Isis has changed theformulations of its antisense cytomegalovirus retinitisdrug, ISIS 2922, and resumed patient accrual in twoPhase III trials. The trials were stopped because ofadverse events. (See BioWorld Today, May 15, p. 1.) n

-- Jim Shrine

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