August 1, 2006 (Vol. 26, No. 14)

Through Acquisitions and Alliances, Firm Plans to Provide Wide Range of Drug Discovery Services

In June, Galapagos ( acquired the drug discovery services operations of Discovery Partners International (DPI; in a deal that, Galapagos maintains, has made it one of top-five drug discovery services companies worldwide.

The E4.25-million cash acquisition includes the assets of all four DPI drug discovery services sites in San Diego and S. San Francisco, Allschwill, Switzerland, and Heidelberg, Germany, along with a DPI sales office in Tokyo. Galapagos is keeping all current DPI sites fully operational and is merging them into its BioFocus drug discovery services division, which will take over scientific management of the DPI sites and their current service contracts. As a result of the integration, BioFocus is changing its name to BioFocus DPI (

The acquisition comes just days after Galapagos announced a major drug discovery and development alliance in osteoarthritis with GlaxoSmithKline (GSK; Through the collaboration, Galapagos will develop new drug compounds against GSK’s portfolio of validated osteoarthritis targets, up to the Phase IIa trials stage.

GSK then has the exclusive option to further develop and commercialize compounds on a worldwide basis. The deal includes a E4-million upfront payment and could bring Galapagos a potential E3-million equity investment and up to E130 million in success-based milestones for two marketable products. A substantial part of the development program will be contracted by Galapagos to its BioFocus DPI division.

Ten months after its acquisition in October 2005 by Galapagos, BioFocus has signed over 10 new target and drug discovery agreements, including deals with Serono, Idenix, Amgen, Boehringer Ingelheim, BASF, and Roche.

Most recently, BioFocus DPI signed a collaboration with Indus Biosciences( and ProCitius (, both based in India, to boost its medicinal-chemistry capabilities even further.

Through the new deals, the Indian companies will carry out chemistry services for BioFocus DPI. The outsourcing agreements complement the acquisition of DPI’s drug discovery operations, providing additional chemistry resources to complement internal capabilities, comments Omno van de Stolpe, CEO and founder of Galapagos.

BioFocus DPI offers a range of integrated capabilities in medicinal chemistry, in vitro biology, cheminformatics, and bioinformatics, which combined provide a variety of approaches for the rapid identification and development of small molecule leads.

“The combination of expertise now means Galapagos and BioFocus provide a service offering that stretches from the initial identification of protein targets in any therapeutic area, through to the delivery of promising preclinical candidates, with the advantage of being able to start the drug discovery process with disease-relevant human primary cell models,” notes van de Stolpe.

Complementary Technologies

Galapagos had a long-standing relationship with BioFocus prior to its acquisition of the company, as a result of collaborative work on Galapagos’ rheumatoid arthritis kinase target program. “Acquiring BioFocus has provided Galapagos with unique capabilities in drug discovery, including specialized compound library and lead optimization/chemistry technologies that perfectly complement our existing expertise in target discovery and validation” adds van de Stolpe.

Core Areas of Expertise

BioFocus has three core areas of expertise compound libraries, informatics, and assay developmentin primary druggable target areas. The SoftFocus GPCR, kinase, and ion-channel screening libraries are complemented by custom library-design capabilities, and specialized chemistry and informatics technologies for hit-to-lead optimization in these target fields are backed up by flexible assay development and HTS.

Higher Hit Rates

The SoftFocus compound libraries represent a major revenue driver for BioFocus. Each SoftFocus library comprises around 1,000 high-purity compounds, built on single or multiple scaffolds, and designed using the company’s Thematic Analysis technology.

Thematic Analysis is a predictive and knowledge-based technology that specifically associates defined topological patterns within families of receptors to key structural features of molecules, facilitating the rational design of GPCR lead-finding libraries and rapid GPCR hit-to-lead optimization, the company reports.

BioFocus contends that the approach ensures that the libraries generate higher hit rates than conventional options and due to their inherently low molecular weights, offer superior chemical starting points for the hit-to-lead phase of drug discovery.

C-Nucleoside Libraries

In late 2005, BioFocus expanded the scope of its SoftFocus range with the launch of its first C-Nucleoside library, which quickly became the fastest-selling library BioFocus has ever developed. Consequently, the company just launched a second C-Nucleoside library and has plans to introduce a third.

Another diversification was the recent launch of an azetidine-based library for GPCR drug discovery. This was also pre-designed using the Thematic Analysis technology and features a bisubstituted azetidine scaffold.

In a further expansion to its offerings, BioFocus introduced a new brand of compound libraries, based on its ThemePair approach. This created an opportunity for drug researchers to find ligands that bind to proteins without having to invest in specialized structural biology assay techniques. The approach bridges the gap between screening small molecular weight ligands, which requires structure-based assays to show any affinity at millimolar concentrations, and the screening of higher molecular weight compounds, which often requires large numbers of such compounds to be screened at low micromolar concentrations to find hits.

As a result of its December 2005 alliance with Cresset BioMolecular Discovery (, BioFocus is also developing a library of FieldFocus-based compounds, designed using Cresset’s molecular-field modeling capabilities.

The technology essentially identifies the molecular field of the 3-D conformation of a compound, providing what the company describes as a powerful protein’s view of the key molecular features required for biological activity and resulting in a structure-independent method of identifying chemical classes. This technology is especially valuable for certain classes of receptors, such as GPCR and ion channels, which lack sufficient x-ray crystallographic structures to allow easy molecular design.

For kinase drug discovery, the company has developed a dedicated Kinase Toolkit, comprising an integrated suite of cheminformatic, bioinformatic, and structural and medicinal chemistry technologies and databases, expediting both the design of libraries of kinase inhibitors for hit generation and downstream hit-to-lead or lead optimization centered on specific kinases.

Target Discovery

BioFocus’ technologies complement Galapagos’ adenoviral-based target discovery platform, the companies report, which allows the introduction of human gene sequences into a wide variety of human cells to knock-in or knock-down specific proteins. The approach starts with development of a human primary cell-based assay that models the disease pathway of interest.

Adenovirus-based gene-expression collections, including knock-down (SilenceSelect) and full-length over-expression (FLeXSelect) libraries, are then screened in the assay, the primary screen, to identify those genes coding for protein products that alter the disease pathway. Selected secondary validation assays confirm the role of hit genes in modulating the disease phenotype.

Galapagos itself is a major customer of BioFocus, utilizing its discovery, chemistry, and optimization skills for in-house programs, focused primarily on bone and joint diseases.

“We have entered the lead-optimization stage in our rheumatoid arthritis program, and the BioFocus technologies are enabling us to fast-track development of our lead candidates,” van de Stolpe comments. “In addition to progressing our programs, based on our targets, Galapagos is also looking to in-license or acquire a promising candidate that is close to or already in clinical development with the aim of being in the clinic by early 2007.”

The adenoviral collections and screening technology, while forming the basis of Galapagos’ internal target discovery activities, are also available through services and collaborations offered by BioFocus.

“Combined with BioFocus’ existing technologies, the addition of our target-identification capabilities means the services division represents a true one-stop shop for all stages of target discovery and validation, right through to optimizing leads for preclinical development,” van de Stolpe remarks.

“BioFocus is showing healthy growth, and with the pharma industry increasingly looking to outsource its drug discovery operations, the opportunities for further increases in service revenues are significant.

“Our alliance with GlaxoSmithKline also fits well into our strategy to provide turn-key drug discovery services to the biopharmaceutical industry. With this first broad alliance, we have started to realize the strategic synergies of combining BioFocus’ drug discovery capabilities with Galapagos’ target discovery engine.”

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