MARTINSRIED, Germany - 4SC is a chemistry- and computer-oriented life science company developing novel compounds against several disease targets using a new "data topology" approach. The company completed a DM 4.5 million (US$2.35 million) initial financing and started its operations this autumn with a staff of 12.

"We are addressing one of the key bottlenecks in drug discovery: the selection of target-binding compounds for synthesis and testing out of billions of possible ones," Ulrich Dauer, head of business development at 4SC, told BioWorld International. "We have developed a proprietary, virtual high-throughput screening technology that allows us to screen several million candidate substances from libraries of already existing compounds within a couple of days, and to rank them according to prospective performance.

"With our system, we get hit rates of 20 percent compared with 1 [percent] or 2 percent in ultra-high-throughput screening processes."

4SC was founded in 1997 in W|rzburg, but decided to move to Martinsried, one of Europe's fastest growing biotech areas. 4SC's "4SCAN" technology platform combines combinatorial synthesis, chemical informatics and an in silico screening technology to reach a unique throughput capacity. A fast-growing computer database comprising a compound library of small molecules serves as the source for the virtual screening. For an entry, compounds have to be easily accessible, cheap, and have to have an empirical drug likeness. The library can be screened by structural- and relational-based queries.

Using structural information from a target protein, proprietary algorithms predict the biological activity in relation to a given target for all molecules of the library. "We call this structure-activity relationship [SAR]. However, if the target protein is unknown, the system can derive the necessary information from compounds that are already known to have an activity profile against that target," Dauer explained. "This calculation is based on a quantitative SAR approach, a statistical method to detect and quantitatively describe relations between chemical structures and biological activity."

The technique makes use of a docking method that fits molecules into receptor cavities. Based on calculated interaction energies, the algorithm can perform a ranking of the docked molecules.

"So starting from a similarity analysis, i.e. the sorting of the library with respect to structural and pharmacophoric similarities, our algorithm ranks the compounds according to their activity," Dauer said. "We do not need to calculate every single molecule, but we interpolate regions of low activity, so that we save approximately 96 percent of calculation time." 4SC had shown in validation projects, he said, that active molecules can be identified in a data set of several million molecules.

To generate early revenues, 4SC will contribute its proprietary technology to research projects on a service- or risk-based model. "Our proprietary cheminformatics technology is our main asset," Dauer said. "It secures a competitive edge and provides us with a flexibility to quickly react to changing market trends and to generate revenues through multiple business channels like contract research, technology transfer or licensing.

"However we are not a technology company," Dauer stressed. "We will develop drug candidates against targets we obtain through acquisition from biotech companies or through research cooperation with academic institutions." Candidates identified by 4SC's technology are being synthesized by partners and subjected to assay system partners. "We will then license the compounds to pharmaceutical companies immediately before or after clinical Phase I or II trials." Among the partners are the University of Heidelberg, Germany, and the Institute for Drug Research, of Budapest, Hungary.

One of the first targets 4SC has chosen is a Na+/H+ exchanger (NHE) active in several plasmodia-causing malaria, toxoplasmosis and leishmaniasis. NHE resides within the protozoa's plasma membrane and performs several key functions, including pH and cell volume regulation.

"These diseases are not a very huge market, but a major health problem," Dauer said.

Michael Lanzer, a member of 4SC's advisory board, is an international expert in parasitology and holds a key patent on the use of NHE inhibitors for the treatment of parasitoses in man.

Already, NHE-targeting substances are used in a number of therapies, such as for hypertension and several cardiovascular conditions. "It is our aim to optimize the pharmacological properties of NHE inhibitors in order to produce a safe and effective drug for the therapy of malaria and other protozoa-caused diseases," Dauer said.

4SC plans to raise DM 20 million this year in a second financing round. "During the next four years, we want to extend our product pipeline to six compounds and hope to be able to develop two of them into the clinical stages," he said. "By then, we can think about an IPO."