Isis Pharmaceuticals Inc. broadened its antisense researchcollaboration with Switzerland-based Ciba-Geigy Ltd. ina deal the California company said could be worth $100million, including anticipated royalties.

Isis, which has registered to sell 3 million shares in apublic offering, could not discuss financial details of thecollaboration. The company has indicated it will receiveresearch and development funding, milestone paymentsand double-digit royalties on products in the agreement.But it has not said how much of the expected incomefrom Ciba will be derived from potential drug sales.

A portion of the estimated $100 million pact is acommitment from Ciba to purchase $7 million worth ofstock from among the shares Isis is selling in its follow-on offering. Ciba, which already owns 1.5 million Isisshares, would receive about 550,000 new shares based onthe $12.75 closing price Friday of Isis' stock(NASDAQ:ISIP). Isis' shares ended the day down 38cents. With 2 million shares Ciba would own about an 8percent stake in Isis. Following its offering of 3 millionshares, Isis will have 25 million shares outstanding.

Ciba and Isis have been collaborating since 1990 onantisense inhibitors targeting a multi-gene familyinvolved in cancer growth. In February, the companiesextended that agreement another three years andidentified a compound, ISIS 5132/CGP 69846A, fordevelopment. However, Isis officials did not detail thedrug candidate's target.

Ciba's expanded drug discovery program is aimed atanother multi-gene family, called protein kinase C (PKC),which is implicated in inflammatory diseases as well ascancer. Isis has identified a compound, ISIS 3521, andexpects to file an investigational new drug application bythe end of 1995 with the FDA to begin clinical trials. Thedrug candidate is an antisense inhibitor of PKC-alpha andwill be developed as an anticancer drug.

Isis' antisense technology is aimed at inhibiting thefunction of messenger RNA and preventing theproduction of disease causing proteins. n

-- Charles Craig

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