BioWorld International Correspondent

Early stage Danish biotechnology firm Symphogen A/S raised US$15 million in first-round financing to develop polyclonal antibody technology it licensed from Boston University.

Symphogen CEO and co-founder Kirsten Drejer told BioWorld International that the Copenhagen-based company is open to extending the current round to the right kind of investor. “If we can identify another strategic international player then we would be willing to include another US$5 million,” she said, adding that US$20 million would satisfy the company’s cash requirements for three years.

Medicon Valley Capital, of Copenhagen, led the financing round. U.S. fund Essex Woodlands Health Ventures also participated, along with Danish investors Novo A/S, L nmodtagernes Dyrtidsfond, V kstfonden and Danske Bank. The company, which has been operating for 18 months, previously raised around US$1 million in seed funding and soft loans from Novo and the Danish government, respectively.

Drejer, a 20-year veteran of the pharmaceutical industry, held a succession of scientific and managerial posts at Novo Nordisk A/S, of Bagsvaerd, before founding Symphogen along with Chief Scientific Officer John Haurum and Chief Financial Officer Thomas Feldthus. The company has an exclusive worldwide license to commercialize a new form of antibody phage display technology developed and patented by Jacqueline Sharon at Boston University Medical Center in Massachusetts.

The Symphage platform generates purified recombinant polyclonal antibodies or “symphobodies” against complex antigens.

DNA fragments encoding variable light (VL) and variable heavy (VH) chains of antibodies are isolated from the B lymphocytes of immunized humans or from immunized transgenic animals, amplified by PCR, and then cloned into a phage display vector. When this is used to superinfect E. coli bacteria, each resulting phage particle expresses a pair of antibody fragments corresponding to the VL and VH chains of the native antibody on its surface.

Large libraries of antibody variable region genes, comprising 10⁷ to 10¹⁰ clones, can be built up with this method. Antigen-binding clones can then be isolated by simple affinity purification. The resulting sub-libraries are then enriched with clones that recognize the different epitopes on the target antigen. Additional genetic components can be added, resulting in the production of full antibody molecules from transformed eukaryotic cells.

Symphobodies, according to Symphogen, have potential as superior and safer alternatives to blood-derived immunoglobulins, which carry the risk of viral contamination. Unlike monoclonal antibodies, which recognize only a single epitope, the technology mimics the immune system by generating a polyclonal mixture of human antibodies.

“Having been in drug discovery for many years, I know that it is wise to try and imitate the way nature works,” Drejer said.

However, Symphogen does not plan to take monoclonal antibody development firms head on. “I think it’s important to stress that we don’t see ourselves as competitors to [companies developing] monoclonal antibodies,” she said. She positions symphobodies as an alternative to monoclonal antibodies in settings where the latter are not effective.

The company’s main clinical targets are infectious disease and allergy. However, its lead project focuses on organ transplant rejection. “We should be able to enter Phase I clinical trials in 2004,” Drejer said. The company aims to develop a therapy superior to existing immunosuppressive treatments, such as the anti-thymocyte rabbit immunoglobulin preparation Thymoglobulin developed by SangStat Medical Corp., of Fremont, Calif., and Atgam, a preparation of equine anti-thymocyte immunoglobulin marketed by Pharmacia Corp., of Peapack, N.J. These can be administered only acutely, as the antibodies they contain are themselves foreign.

Its second program, at an earlier stage of development, concerns the topical administration of polyclonal antibodies for treatment of allergy to cat dander or house dust mites. “That is a totally brand new concept,” Drejer said.