BioWorld International Correspondent

Austria's flagship biotechnology company, Vienna-based Intercell Biomedical Research & Development AG, raised EUR27 million (US$25.3 million) in second-round funding from a consortium of European investors led by Apax Partners, of London.

Techno Venture Management (TVM), Nomura International plc, GO Equity GmbH, Sal. Oppenheim Jr. & Cie and Alpinvest NV also participated in the deal.

Intercell, which is developing synthetic vaccines for infectious diseases and cancer, aims to use the cash to accelerate its internal development programs, fund clinical trials and automate its genomics-based antigen identification program, CEO Alexander von Gabain told BioWorld International.

Intercell is the first spin-off company to emerge from Vienna Biocenter, a center of excellence in basic life sciences research established in the 1980s. Von Gabain and Max Birnstiel, former director of the Institute of Molecular Pathology in Vienna, founded the company in late 1997 along with scientific staff Michael Buschle, Walter Schmidt and Aaron Hirsh. It raised EUR6 million from Munich-based TVM in 1998, plus additional cash from local investors.

Intercell's first candidate vaccine, for hepatitis C, entered Phase I clinical trials with 30 healthy volunteers in September, and initial results have been promising, von Gabain said. Phase II trials are due to commence in early spring, he said. The company has two other candidate vaccines in its immediate pipeline, which are likely to enter the clinic during the year.

"The second clinical study we have on the way is in collaboration with the Ludwig Institute of Cancer Research," he added. This involves a tumor antigen the not-for-profit research body identified, which is associated with breast and ovarian cancer and with melanoma. The company also is lining up a third clinical trial, in collaboration with Sequella Inc., of Rockville, Md., involving a Mycobacterium tuberculosis vaccine.

Intercell, in collaboration with The Institute of Genomics Research (TIGR) in Rockville, has developed a genomics-based approach to antigen identification. It involves the creation of gene libraries that contain clones expressing short fragments of target DNA, corresponding to potential epitopes or antibody recognition sites on full proteins. Each fragment is expressed on the cell surface of a host E. coli strain as part of a fusion involving a phage receptor protein, which is encoded by the same vector construct. Each clone is screened against the serum of patients who have mounted a successful immune response to the target organism, and promising candidates are then selected for further development.

Intercell demonstrated proof of concept with the technology by identifying 60 novel Staphylococcus aureus antigens. It has since progressed to additional Staphylococci species and also plans to screen Helicobacter in the short term. "This antigen identification program has enormous potential to create short-term business with big pharma," von Galbain said.

At present, the company does not plan to work on more than four clinical development programs, and it will license out other targets for further development. Discussions with prospective partners have already commenced, he said.

The company also is looking for antigens common across multiple species and for what von Galbain called "culprit bacterial candidates" that could play a role in autoimmune disease.

The second pillar of its technology platform is a simple homopolymeric peptide, which plays a key role in stimulating an immune response.

"We discovered by serendipity that polyarginine is a perfect mimic of signals of the innate immune system," von Gabain said. The peptide has an immunostimulatory effect similar to that of defensins, a class of bioactive peptides that promote macrophage migration to sites of infection and subsequent antigen uptake and presentation to B cells, which produce antibodies, or T cells, which mediate cellular immunity. Polyarginine is, therefore, an important structural component of Intercell's vaccines. It also will make manufacturing relatively straightforward, von Galbain said, as all that is required is an understanding of basic protein chemistry.