Hit Discovery Constance GmbH (HDC) searches for new drug candidates on behalf of academic institutions and the pharmaceutical industry. Established in early 2014 on the Konstanz Campus (former Takeda/Nycomed/Altana research site), the joint venture organization offers high-throughput screening and compound management and storage services to support the transfer of academic research into the development of new medicines. With its high-throughput screening stations and its vast compound collection, HDC, along with Axxam, which is one of the organizations involved in the joint venture, is one of the largest screening centres in the world.
There is often a huge gap between academic drug discovery research and industrial drug development, and this gap prevents new research results from being turned into new drugs. It often takes well over ten years from the discovery of a target molecule that plays a role in a disease and the identification of drug candidates that affect this target molecule to placing a new drug on the market. In the end, less than one percent of all drug candidates that arise from screening and research are placed on the market, which means that the implementation of research results carries a high financial risk. “It is this gap between research and industry that HDC is trying to close,” says Dr. Jan Eickhoff, CEO of HDC. The company specializes in hit discovery, i.e. the identification of compounds that are suitable as drug candidates, which is a very early step in the drug discovery process. Hit discovery involves the high-throughput screening (HTS) of large compound libraries for suitable compounds. Depending on the issue being addressed, hits from these screens are then tested in specific assays for desired activities, e.g. the compounds’ ability to bind to and activate a surface receptor or to inhibit a particular enzyme. They are also analyzed in greater detail in additional tests. HTS only involves a test concentration or a single assay and further tests need to be performed in order to find out whether the compound of interest also shows the sought-after activity under slightly altered conditions, in a different assay or using a different analysis method. “For example, a compound found to be active against the selected target under cell-free conditions, is re-tested in a cellular environment to find out whether it shows the same activity as before,” says Dr. Eickhoff. The quality control involving special, successive tests is relatively complex and is crucial for the further use of the compounds. The HDC team has broad expertise in this area in particular. In contrast to simple primary screening hits that are found positive in just one test system, there are so-called “confirmed hits” which demonstrate the desired activity in several subsequent test systems. This profiling increases the quality of the hits, which makes them promising candidates for the client who then develops them into drugs for therapeutic use. “The high quality also enables a faster implementation of the results obtained,” adds Eickhoff.
In addition to HTS, the composition of the compound library is the basis for the discovery of new drug candidates. HDC’s library consists of more than 240,000 drug- and lead-like compounds which have been collected by a team of medicinal and computational chemists with many years of screening experience. “These new compounds possess excellent physicochemical characteristics and easy synthetic accessibility,” says Eickhoff.
Thanks to HDC’s infrastructure for automated compound management, the individual test compounds can be combined for experiments. Alternatively, HDC can also handle and screen client compound collections. In addition to carrying out high-throughput screens (HTS) using conventional biochemical, cellular and radiometric assays, HDC also offers the development of specific assays, phenotype-based screening using fully automated, unattended high-content screening (HSC) based on microscopy, as well as the storage and management of compound libraries. HDC performs these tasks with three fully automated screening stations as well as a fully automated compound library with a storage capacity of 20 million compounds at -20°C. “The facilities in Konstanz are unique in Germany and allow us to offer technologies that are not otherwise available in this form,” explains Jan Eickhoff.
As the company’s HTS stations are approved for biosafety level 2, HDC can also address issues related to infectious diseases. “All these factors make HDC one of the largest screening hubs worldwide,” Eickhoff adds. In addition to offering screening services, HDC also has the potential to carry out research projects in the field of technology development.
The history of the foundation of HDC goes back to 2010. It was a time when cooperation agreements like the one between the pharmaceutical company Nycomed and the Lead Discovery Center (LDC) in Dortmund, established by the technology transfer organization Max Planck Innovation in 2008, were still unusual. At that time, Nycomed and LDC were already carrying out cooperative screening projects in the Nycomed (formerly Altana) laboratories in Konstanz. Following the acquisition of Nycomed by the Japanese pharmaceutical company Takeda in May 2011, the research units were relocated due to the restructuring of the Konstanz company site.
As the changes at the research site in Konstanz were emerging, the Dortmund LDC decided to retain the screening facility as a functional unit with all available technical options. “The screening and compound management department, including devices and personnel, has been built up over many years. The existing on-site infrastructure, along with the team of experts, is a closed unit in which all the individual components are key for it to work,” says Eickhoff. In addition, the facility's central location in Europe and its proximity to the pharmaceutical location of Basel (CH), are positive location factors for the start-up company. In order to be able to extend the screening and compound management department beyond internal use and to provide other institutions with access to this infrastructure, Hit Discovery Constance was established as an independent joint venture organization between Axxam SpA (Milano, Italy) and the Centre for Drug Design and Discovery (CD3) of the Royal University of Leuven in Belgium in 2013. “The support from the city of Konstanz and the presence of regional networks have played a major role in convincing the parent companies of the attractiveness of investing in the area,” concluded Eickhoff.
Doris HafenbradlHit Discovery Constance GmbH (HDC)Byk-Gulden-Str. 278467 KonstanzTel.: +49 (0)7531 / 1273-149E-mail: doris.hafenbradl(at)hit-discovery.de