Hybridon Inc., an antisense drug discovery company, grossed $50million _ half of it from European investors _ in the first major1996 biotechnology initial public offering (IPO), which also is one ofthe largest market debuts of the last several years.

The company sold 5 million shares for $10 each, which was midwaybetween the proposed price range of $9 and $11. Following theoffering the company has 23.7 million shares outstanding.

Underwriters Lehman Brothers, of New York, and Paribas CapitalMarkets, of London, have options to purchase another 750,000 sharesto overallotments. If those shares are sold, the IPO would reach $57.5million.

Hybridon (NASDAQ:HYBN) closed Thursday at $10.50.

Myriad Genetics Inc., of Salt Lake City, made the largest debut of1995 in the public markets, grossing $53 million through the sale ofnearly 3 million shares, including options for overallotments, at $18per share. Following the IPO, Myriad Genetics, a genomics company,had more than 8 million shares outstanding.

The Hybridon IPO also eclipsed all initial offerings in 1993 and1994, according to surveys in the annual BioWorld BiotechnologyState of the Industry Report for those two years.

In 1994, Quintiles Transnational Corp., a contract researchorganization in Research Triangle Park, N.C., generated the mostfunding with an IPO that grossed $39 million. The year before,Shaman Pharmaceuticals Inc., of South San Francisco, and CelltechGroup plc., of Slough, England, tied for the biggest IPO with $45million in gross proceeds raised.

Hybridon registered for the public stock sale in November 1995 andcompleted it a week after signing a collaboration worth a potential$200 million with G.D. Searle & Co., of Skokie, Ill., a subsidiary ofSt. Louis, Mo.-based Monsanto Co. (See BioWorld Today, Jan. 18,1996, p. 1.)

In the prospectus filed with the Securities and Exchange Commissionfor the IPO, Hybridon had about $13 million in cash as of Sept. 30,1995, with a net loss for the first nine months of the year of $23.7million.

Hybridon's antisense technology involves using syntheticoligonucleotides that bind to a targeted messenger RNA, preventingthe expression of disease-associated proteins, such as those involvedin replication of HIV and growth of cancerous tumors.

With each discovery of a disease-causing gene and its DNAsequence, the possibility exists for creating an antisense compound tocancel out that specific gene's deleterious function.

Isis Pharmaceuticals Inc., of Carlsbad, Calif., and Hybridon areconsidered the most advanced companies in research anddevelopment of antisense compounds.

Hybridon's lead compound, GEM 91, is in Phase Ib/II testing in theU.S. and France for AIDS. GEM is an acronym for gene expressionmodulation. GEM 91 targets the gag gene in HIV to prevent it fromencoding a protein used in replication of the AIDS virus.

Five other compounds are in preclinical development. Two alsotarget AIDS and one of the compounds is being developed as a pillfor oral administration. A third compound is aimed atcytomegalovirus retinitis, the fourth is directed at cancer and the fifthis designed to battle retinopathy.

Hybridon expects to file investigational new drug applications thisyear to begin clinical trials of another HIV intravenous drug and acancer compound.

The Searle agreement covers use of Hybridon's technology todevelop antisense compounds for eight molecular targets identifiedby the pharmaceutical firm as regulators of immune systemresponses.

Hybridon also has collaborations with Roche Holdings Ltd., of Basel,Switzerland, Medtronic Inc., of Minneapolis, and Pharmacia &Upjohn Co., of Kalamazoo, Mich. n