DUBLIN, Ireland - Danish start-up company Exiqon A/S is raising a second tranche of investment to spin off a company to develop therapeutic applications of its nucleic acid analogue technology, locked nucleic acids (LNA).

Den Danske Bank, of Copenhagen, is acting as agent in a private placing with Danish institutions, said Mikael Oerum, CEO of Exiqon, which is based in Vedbaek, north of Copenhagen. He expects to conclude the investment round in September, he said, and the new company, with separate management, should be in place shortly afterwards.

Exiqon will continue its current work on diagnostic, research and monitoring applications of the technology, which originally was developed by Jesper Wengel, a professor at the University of Copenhagen, and his research student Poul Nielsen, who is based at Odense University.

Exiqon, which was established in 1996, aims to bridge the worlds of organic chemistry and molecular biology. Its four founding directors, Mikael Oerum, his brother Heinrik, Mogens Hausteen Jakobsen and Troels Koch, hold 50 percent of its equity.

The remainder is held by the Nobel family, of Copenhagen. It has decided to spin off a company to enable it to maintain its current focus on the diagnostic arena, said Oerum.

Exiqon has a second proprietary technology, a photochemical coating technique that promotes covalent coupling of molecules to both natural and synthetic polymer surfaces.

Exiqon is outright owner of the LNA technology, said Oerum. Wengel is working with the company as a consultant.

LNA molecules, which consist of 2'-O,4'-C-methylene bicyclonucleoside monomers, obey Watson-Crick base pairing rules but display enhanced binding affinities to complementary DNA and RNA sequences.

Wengel and coworkers at the University of Copenhagen, Odense University and The Royal Veterinary and Agricultural University, in Frederiksberg, reported earlier this year on increases ranging from 3 degrees Celsius to 8 degrees Celsius in the thermal stability of duplexes containing LNA and either DNA or RNA, compared to unmodified controls.

Their paper, titled “LNA (locked nucleic acids): synthesis of the adenine, cytosine, guanine, 5-methylcytosine, thymine and uracil bicyclonucleoside monomers, oligomerisation, and unprecedented nucleic acid recognition,“ appears in Tetrahedron, Vol. 54, p. 3607.

Exiqon signed an option agreement in February with Amersham Pharmacia Biotech, of Uppsala, Sweden, which is investigating the use of LNA as a research tool. The initial agreement runs until the beginning of September. Exiqon hopes to conclude a more substantial agreement then.

“From a technology point of view, they have already gone through an extensive evaluation program with this,“ said Oerum.

Exiqon also is collaborating on a cancer program with the Cancer Research Foundation, of Copenhagen, a private research institute. The partners are investigating the potential of LNA molecules to act as antisense therapeutics. The program eventually will be handed over to the new company Exiqon plans to set up, but clinical development of any lead compounds will also require an external partner, said Oerum.

Several diagnostics companies, which Oerum declined to identify, and Rochester, N.Y.-based Nalge Nunc International Corp., which makes laboratory supplies, have licensed Exiqon's photochemical coating technology.

Exiqon has also applied it to the development of a Salmonella screening system, in collaboration with Denmark's national veterinary laboratory. This is being used in a national screening program for the bacterium in slaughtered pigs.

In addition, the company has an ongoing program that aims to integrate its two core technologies. “Arrays would be an obvious target in combining these two technologies,“ Oerum said. *