Leif Helth Jensen, one of six founders of the flagship Danish biotechnology firm NeuroSearch A/S, has left the company to head a start-up developing therapeutic applications of a nucleic acid analog technology called Locked Nucleic Acids (LNA). The new company, Cureon A/S, of Copenhagen, is finalizing first-round funding of DKK 100 million (US$11.5 million) from Nordic investors, Jensen told BioWorld International. This will be sufficient for three years, he said.
Cureon is a spin-off from Vedbaek-based Exiqon A/S, which owns the LNA technology but which is focusing on diagnostic applications. Exigon is assigning all therapeutic rights to Cureon, in which it will hold a non-controlling interest. The spin-off had been planned for some time (see BioWorld International, June 3, 1998, p.1). Cureon was finally established last December, and Jensen joined the company last month.
The new company is building antisense programs in two broad areas, cancer and immunology. Its lead program is in the allergy field. Jensen said his goal is to take an initial compound into the clinic late next year or early in 2002.
"We will license out on a gene-by-gene basis all other targets," he said. Cureon will build an additional revenue stream by offering target validation services to drug discovery companies, he said. He said he hopes to secure the first contracts in these two areas next year.
Denmark has a strong science base in the area of nucleic acid analog technology. Jesper Wengel at the University of Copenhagen originally developed the LNA technology, while another group - which includes Ole Buchardt, Peter Nielsen and Michael Egholm from the University of Copenhagen, along with Rolf Berg of the Riso National Laboratory - developed an alternative technology, Peptide Nucleic Acid (PNA), which was licensed to Isis Pharmaceuticals Inc., of Carlsbad, Calif. The latter subsequently licensed back the technology to Copenhagen-based Pantheco A/S for applications in the anti-infective area.
Although Isis already has one niche antisense drug on the market - Vitravene (fomivirsen) for treatment of cytomegalovirus retinitis in AIDS patients - and is in clinical trials with several others. Jensen said he is "extremely optimistic" about Cureon's chemistry.
LNA differs from standard nucleosides in having a methylene linker that connects the 2'-O position to the 4'-C position, restricting the usual conformational freedom of the furanose ring in such molecules.
Wengel and co-workers recently reported data that suggest LNAs have high in vivo efficacy without exhibiting the toxic effects associated with phosphorothioate-containing DNA analogs, underpinning their potential in therapeutic as well as functional genomics applications. Claes Wahlestadt was lead author on the paper, titled "Potent and nontoxic antisense oligonucleotides containing locked nucleic acids," which appeared in Proceedings of the National Academy of Sciences, dated May 9, 2000. The group reported that co-polymers of LNA and DNA resisted degradation in blood serum and cell extracts, but were capable of activating RNase H, which is important in actuating antisense effects.
They also found that LNA analogs did not cause detectable toxic reactions in rat brain, while LNA-DNA copolymers displayed strong antisense activity in assay systems such as a G-protein-coupled receptor in living rat brain and an E. coli reporter gene. Earlier data indicated the very high thermal stability of duplexes containing LNA and either DNA or RNA.