Coming off the biggest deal in its history, Isis Pharmaceuticals Inc. filed to sell 5 million shares of common stock that based on Monday?s closing price of $18.30 would raise $91.5 million.

Isis? stock (NASDAQ:ISIP) fell 32 cents Tuesday to close at $17.98. At the end of the second quarter, Isis had about $106 million in cash and cash equivalents. It has about 40.9 million shares outstanding.

UBS Warburg LLC, of Stamford, Conn., is serving as the only book-running manager for the offering. Robertson Stephens Inc., of San Francisco; Needham & Co. Inc., of New York; and Fortis Securities Inc., of New York, are serving as co-managers. Underwriters have an option to purchase 750,000 shares to cover overallotments.

The offering comes after Isis? deal with Eli Lilly and Co., of Indianapolis, in August ? a deal with a potential worth of more than $400 million ? drove its stock up 48 percent on the day the news was released, closing at $14.89. Some analysts in the industry saw the weighty deal with Eli Lilly as a strong validation of Isis? antisense technology. So while the market is treating others unkindly, Isis? stock climb provides reason for the Carlsbad, Calif.-based company to conduct a public offering. (See BioWorld Today, Aug. 23, 2001.)

In the spring, Merck & Co. Inc., of Whitehouse Station, N.J., licensed Isis? preclinical Type II diabetes drug candidate, ISIS 113715, for up to $50 million. The compound is an antisense inhibitor of the gene that encodes PTP-1B, a negative regulator of insulin receptor signaling. Days later, Isis and Hybridon Inc., of Cambridge, Mass., disclosed an agreement allowing Isis to license all of Hybridon?s antisense chemistry and delivery patents. In return, Hybridon was allowed access to Isis? RNase H suite of patents. With all the giving and taking considered, Hybridon netted about $28.5 million. Isis? CEO, Stanley Crooke, said at the time the deal with Hybridon ensured Isis of owning ?everything that is important in antisense.? (See BioWorld Today, May 24, 2001, and May 29, 2001.)

In July, Isis signed a deal for its GeneTrove division. Through an agreement with Celera Genomics, of Rockville, Md., Isis? division will identify the roles of more than 200 genes for Celera. Financial details of that deal were not disclosed. (See BioWorld Today, July 17, 2001.)