Galapagos

 

Galapagos

Galapagos has discovered drug targets (starting points for the development of novel drugs) using
cells from patients for more than fifteen diseases. These targets form the basis of drug discovery
programs aimed at identifying small molecules or antibodies that alter the activity of these proteins,
thereby potentially changing the course of the disease. By studying the disease process and key
points of intervention, it is our goal to develop new drugs that stop the disease rather than just
treat the symptoms.
Galapagos is progressing one of the largest pipelines in biotech, with three Phase 2 programs,
two Phase 1 programs, five pre-clinical, and more than 20 discovery programs. 

Contact

Richard Janssen
richard.janssen@glpg.com

Jan Stallen

Jan.Stallen@glpg.com

Added value Galapagos for hDMT:

• Input in format of assays
• Validation of assays
• High throughput screening of assays for internal research programs
• Connections with pharma
• Focused approach
• Access to expensive and state-of-the-art equipment (robots, readout equipment)
• Business development expertise


Added value hDMT for Galapagos:

• Access to unique cellular assays
• Access to patient material
• Access to (latest) biology/disease know how
• Access to ONE institute with complementary disciplines

 

Expertise and facilities:

Expertise

• Over 100 in vitro human primary cell-based disease models (lung and skin fibrosis, cystic
fibrosis, bone and joint diseases, inflammation, cancer, metabolic disease, infectious disease).
• Drug target identification and validation
• Drug discovery and medicinal chemistry
• Toxicology
• Animal models for fibrosis, bone and joint diseases, cystic fibrosis, inflammation, cancer,
metabolic disease, infectious disease
• Strong expertise in collaborative research with patient foundations, academic research
institutions, biotech and big pharma
• Strong connections with decision makers and budget holders in big pharma, biotech, and
patient foundations
• Good understanding of patient and market needs

Facilities

• State-of-the-art and ISO-certified ML2 laboratories
• Robotics for automated liquid handling
• High throughput plate reader technology
• High throughput screening
• High content imaging
• High throughput flow cytometry
• Complex (co)-cultures of primary cells
• Adenoviral shRNA libraries
• Compound libraries

 

Ongoing projects:

Development of various organ-on-a-chip assays with Mimetas. Performed with company
research budget. Principal investigator: Richard Janssen
Setting up co-cultures and 3D cultures in the field of metabolic disease, inflammatory
bowel disease, fibrosis, cystic fibrosis, immune-oncology
. Performed with company
research budget. Principal investigator: Richard Janssen
Development of a liver-on-chip. Performed with company research budget. Principal
investigator: Richard Janssen


Examples of established complex cell culture systems:

An IBD-relevant co-culture setup
Co-culture setup of dendritic cells (DC) with polarized colon epithelium established at Galapagos in 96-well format to study inflammatory bowel disease. Human polarized colon epithelial cells are grown on a trans-well insert. Human DC are grown at the bottom of the well. Effects of E.coli on immune cells and epithelium are determined by assessing barrier function of epithelium and by inflammatory responses of DC and epithelium. Role of individual genes in these processes can be identified through adenoviral shRNA-based knockdown of genes of interest in either colon epithelial cells (A) or DC (B).

A high-throughput 3D anchorage independence assay to study cancer growth.
Co-culture setup of tumor cells and mesenchymal cells in soft agar established at Galapagos in 96-well format. Role of individual genes in tumor growth can be determined through individual knockdown using adenoviral shRNA. As shown, knockdown of a positive control gene results in very strong reduction in number and size of colonies in soft agar. Using high content imaging, tumor growth in 3D can be quantified rapidly
and thousands of experiments can be performed. 

Publications:

• Ghotra, V.P.S., He, S., van der Horst, G., Nijhoff, S., de Bont, H., Lekkerkerker ,A.N., Janssen,
R.A., Jenster, G., van Leenders, G.J.L.H., Hoogland, A.M., Verhoef,E.I., Baranski, Z., Xiong,
J. , van de Water, B. , van der Pluijm, G., Snaar-Jagalska, B.E. and Danen, E.H.J. Cancer
Research 2014. In press.
• Lekkerkerker, A.N., Aarbiou, J., van Es, T., Janssen, R.A.. Cellular players in lung fibrosis. Curr
Pharm Des. 2012;18(27): 4093-102. Review.
• Ley, S., Weigert, A., Hériché, J.K., Mille-Baker, B., Janssen, R.A., Brüne, B. RNAi screen
in apoptotic cancer cell-stimulated human macrophages reveals co-regulation of IL-6/IL-10
expression. Immunobiology. 2013 Jan; 218(1):40-51.
• Ley, S., Weigert, A., Weichand, B., Henke, N., Mille-Baker, B., Janssen, R.A., Brüne, B. The
role of TRKA signaling in IL-10 production by apoptotic tumor cell-activated macrophages
Oncogene. 2013 Jan 31;32(5):631-40.
• Moulin, V., Morgan, M.E, Eleveld-Trancikova, D., Haanen, J.B., Wielders, E., Looman, M.W.,
Janssen, R.A., Figdor, C.G., Jansen, B.J., Adema, G.J. Targeting dendritic cells with antigen
via dendritic cell-associated promoters. Cancer Gene Ther. 2012. 19:303-11.
• Camus, S., Quevedo, C., Menéndez, S., Paramonov I, Stouten PF, Janssen RA, Rueb S, He S,
Snaar-Jagalska BE, Laricchia-Robbio L, Izpisua Belmonte, J.C. Identification of phosphorylase
kinase as a novel therapeutic target through high-throughput screening for anti-angiogenesis
compounds in zebrafish. Oncogene. 2012 Sep 27;31(39):4333-42.
• Van Maanen, M.A., Stoof, S.P., van der Zanden, E.P., de Jonge, W.J., Janssen, R.A.,
Fischer, D.F., Vandeghinste, N., Brys, R., Vervoordeldonk, M.J., Tak, P.P. The alpha7 nicotinic
acetylcholine receptor on fibroblast-like synoviocytes and in synovial tissue from rheumatoid
arthritis patients: a possible role for a key neurotransmitter in synovial inflammation. Arthritis
Rheum. 2009 May;60(5):1272-81.

 

Relevant patents:

• EP1022335 High-throughput screening of gene function using libraries for functional genomics applications.
Adenoviral libraries and methods for producing adenoviral libraries
• EP1444346 siRNA knockout assay method and constructs.
shRNA
• US6340595 High throughput screening of gene function using adenoviral libraries for functional genomics applications.
A library of a multitude of unique expressible nucleic acids in adenoviral vectors and a process for producing a library of adenoviral vectors
• US6413776 High throughput screening of gene function using adenoviral libraries for functional genomics applications.
A method of producing a recombinant adenoviral vector library
• US7029848 High throughput screening of gene function using libraries for functional genomics applications.
A method for determining the function of a nucleic acid sequence (method of screening using
adenoviral vectors)