Executive Summary:
Alepharma is positioned in the biotechnology and health care sectors. Its primary corporate goal is to design and to sell innovative drugs at the pre- or post-phase I clinical test stage. The company has proprietary technology that significantly shortens the pre-clinical design process for drugs. Drugs interact specifically with their targets, usually proteins. The technology of Alepharma identifies these specific interactions which are subsequently used to rationally design compounds that lead to drugs. The company uses its intelligent screening technology together with a new software based drug design to rapidly identify new drugs. As an advantage over "brute force" screening technologies (HTS or uHTS) our technology efficiently produces an in depth view of the interactions of the drug with the target. The drugs designed by our technology are highly optimized in that they will be more specific and produce less likely resistance than current pharmaceuticals. The main customers will be pharmaceutical companies that buy or opt to co-develop drugs before or after the first clinical test phase. First drug candidates are ready to enter pre-clinical development. Further targets in virology, cancer, and pain management have been identified. The company combines advanced technology from chemistry, biophysics, genetics, bioinformatics, and molecular biology. In a later stage we plan to further develop the drugs to clinical maturity, register and license them to pharmaceutical partners.
Based on custom technology bioactive molecules will be identified from mixtures. At the same time key anchor groups of these molecules, also called pharmacophores, are characterized and their spatial orientation is defined. The drug screening and design process for new drugs is notably shortened because the information on the spatial orientation of key anchor groups can be used to directly construct lead compounds. Refinement of said leads finally furnishes optimized drugs. In contrast, conventional drug design indirectly extracts such information from the analysis of bioactivity of a multitude of bioactive compounds through quantitative structure activity relationships (QSAR).
The owners have developed nuclear magnetic resonance (NMR) based technology that allows to screen about 50,000 compounds per day for binding affinity to protein or RNA/DNA targets. Importantly, we can use the technology to identify the key anchor groups, i.e. the sections of the ligand in direct contact with the protein target. Furthermore, the three dimensional structure of the compound when bound to the protein target can be characterized. This delivers information about the spatial orientation of the key anchor groups. As an advantage over existing technology, we can screen candidates for lead substances to proteins of unlimited size. The protein may even be an integral part of a membrane or may be bound to a resin for stability and screening speed. Furthermore, no costly isotope labeling of the protein target is required and as little as a few micro grams of protein are sufficient for the technology. As a consequence we can use protein targets that are not normally accessible. The new technology will also allow a continuous screening process with an easy recycling of the protein.
As an example for BioAffinity NMR we have developed a newly designed inhibitor to prevent HIV to infect human cells, a so called entry inhibitor that as such should not lead to any resistance development by the virus. Further we could show that target proteins anchored into membranes and traditionally difficult to utilize in screening protocols can be efficiently used in the current system. Combination of the information on the 3D structure of the ligand combined with the knowledge of the parts interacting directly with the protein results in novel intelligent ways to build custom inhibitors that, when matched to natural ligands should in general be much less prone to the development of resistance. The new strategy uses building blocks for the ligands on the basis of all known ligands to proteins to develop new lead compounds. We plan to establish a company that generates leads for a broad range of targets.
Further expansions will be in use of genetic information in drug design to broaden the use of drugs and to reduce side effects. We also plan to extend our focus to other targets predominantly in the above named fields of virus challenge, cancer, and pain control.
It is emphasized that the company, upon successful establishing its market oriented competence in directed drug design, plans to acquire or merge with companies that have established technology in identifying new targets and a company that has a high efficiency in generating compound libraries on a large scale for optimizing drugs. These acquisitions or mergers will effectively create a large competent company that will become a leader in drug design in terms of speed and quality.