Hybridon Inc., which has raised $108 million privatelysince 1990, is trying to raise another $60 million or sothrough an initial public offering (IPO).

Hybridon, a Worcester, Mass., company focusing onantisense technology, said Tuesday it filed for an IPOproposing the sale of 5 million shares priced between $9and $11 each. Underwriters Lehman Brothers, of NewYork, and Paribas Capital Markets, of London, haveoverallotment options on another 750,000 shares.

Half the shares are being offered in the U.S. and Canadaand half internationally. After the offering, Hybridon willhave about 23.7 million shares outstanding.

Historically Hybridon has raised money in NorthAmerica, Europe and the Near East _ in nearly one-thirdproportions, with a minor part of the financing comingfrom the Far East. The company has collaborationsongoing with F. Hoffmann-La Roche Ltd., of Basel,Switzerland; Medtronic Inc., of Minneapolis; andPharmacia Biotech AB, a subsidiary of Stockholm,Sweden-based Pharmacia AB.

Hybridon's lead compound is a called GEM 91, anantisense oligonucleotide in Phase Ib/II testing in the U.S.and France for AIDS and HIV. GEM (gene expressionmodulation) 91 targets the gag gene in HIV, and preventsit from encoding a protein necessary for HIV replication.

The company has five compounds in preclinicaldevelopment, including GEM 92 and GEM 93, both forHIV and AIDS, with the latter an oral formulation. Theother three compounds are being developed to targetcytomegalovirus for retinitis, protein kinase A for cancerand vascular endothelial growth factor for retinopathies.

Hybridon's antisense technology platform is based onmedicinal chemistries, analytical chemistries andmanufacturing technology.

Company researchers have produced more than 20families of synthetic antisense oligonucleotidechemistries. Hybridon's analytical tools are used toanalyze the chemical purity, base sequencing andcomposition of its oligonucleotides. Its manufacturingtechnology increases the purity, enhances the efficiencyand increases scales of production.

The antisense approach usually involves oligonucleotidesbinding to messenger RNA to prevent production ofdisease-associated proteins. Hybridon is focusing onproducts for which the gene encoding the target protein iswell characterized.

The Aug. 7, 1995, edition of the British journalBiochemical Pharmacology has two papers on an orallyavailable second-generation GEM molecule. One paperdescribes the oral bioavailability, the other its enhancedstability in the body. Both benefits come from cappingthe original DNA molecule at both ends with stretches ofRNA, to prevent degradation, thus creating a hybridnucleotide. (See BioWorld Today, Aug. 9, 1995, p. 1.)

Combining DNA and RNA in one compound increasesthe half life and the affinity for the HIV gag target,company officials said after publication of the papers.

In its prospectus, Hybridon said it plans to fileinvestigational new drug applications in the next year tobegin human testing of two drug candidates: GEM 92(not the oral form) and an oligonucleotide that inhibitsprotein kinase A.

Hybridon and Roche are developing compounds forhepatitis B and C viruses and human papilloma virus(HPV). Roche is funding research and development andwill make milestone payments to Hybridon, one of whichwas met last summer with the identification of a leadcompound for hepatitis C. Clinical plans for thatcompound were not disclosed. But officials at the timesaid oral candidates for hepatitis B and HPV wereexpected to be going into animal studies.

With Medtronic, a medical device company, Hybridonsigned a five-year deal in 1994 involving delivery ofantisense compounds to the brain using Medtronic'simplantable drug infusion system. The companies aretargeting Alzheimer's disease. n

-- Jim Shrine

(c) 1997 American Health Consultants. All rights reserved.