BioWorld International Correspondent

4-Antibody AG raised CHF6 million (US$4.9 million) in a Series A funding round to support its new drug development efforts and named Sijmen de Vries its new CEO.

The Basel, Switzerland-based company was spun out from the University of Basel in 2002 to commercialize a proprietary platform that can both generate monoclonal antibodies de novo and optimize existing molecules.

"The company has completed, more or less, the development of its antibody platform. The next step will be to engage in internal development programs and work with third parties on collaborative projects," de Vries told BioWorld International.

De Vries previously was CEO at Munich, Germany-based Morphochem AG, which was acquired by Vienna-based Biovertis AG late last year. Before that, he held a variety of positions at Basel-based Novartis AG and at SmithKline Beecham. "I think it's a very good place to be - in this young antibody company with an unencumbered platform," he said.

The company's technology was developed at the University of Basel by co-founders Fritz Melchers, Dirk Haasner and Ulf Grawunder. The latter initially was CEO of the company and now has assumed the role of chief scientific officer.

4-Antibody's approach to developing antibodies combines the speed and flexibility of phage display with the high-quality, high-affinity antibodies associated with transgenic mouse technology, de Vries said.

It involves isolating and genetically engineering murine precursor B-lymphocytes to express human gene sequences encoding heavy and light chain variable binding domains of a single monoclonal antibody or of multiple antibodies. "We can very delicately control the type of repertoire we put into the mice," Grawunder told BioWorld International.

The altered cells then are transplanted into mice that are lacking their own B cells. The technique exploits the mammalian immune system's natural affinity maturation process, which ensures that, following successive cycles of B-cell somatic hypermutation, proliferation and selection, those cells expressing high-affinity antibodies are expanded. "Essentially the mouse is a black box for us in terms of how the affinity maturation is being done," Grawunder said.

Phage display also allows developers to work with a controlled repertoire of antibodies, Grawunder said, and it also supports heavy and light chain shuffling. However, immunological and pharmacological properties of antibodies identified in bacterial screening systems can alter when they are introduced to a mammalian cell system, he said. Transgenic mice do not allow the possibility of optimizing existing antibodies, he said, and also can give rise to antibodies that recognize immunodominant epitopes that may be pharmacologically irrelevant. The 4-Antibody system can generate antibodies against difficult targets and against weak epitopes, Grawunder said.

The company is in discussions with potential partners and may sign a deal before year's end, de Vries said. It also is finalizing the selection of the therapeutic areas it will target with its internal programs.

4-Antibody previously raised CHF2.75 million in seed funding from the same consortium that participated in the current round. They include Basel-based Biomedinvest AG; Stuttgart, Germany-based Grazia Equity GmbH; Amsterdam, the Netherlands-based Life Sciences Partners; and Mulligan Biocapital AG, of Hamburg, Germany. The new investment will fund activities until the end of 2007. "I'm not excluding that we may actually take a little more in the near future, as well," de Vries said.