1. Karen Silence
Born 22 March 1969
Married, two children (18-21 ys old)
Belgian Nationality
Introduction
I have been actively involved in the start-up of two biotech companies (Ablynx and arGEN-x).
I was project leader in both companies for the lead projects, taking them from research into
pre-clinical development and eventually in clinical trials. I also participated in business
discussions and grant writing. I have supervised and managed small and large teams of
technicians and scientists.
Professional experience
 Phage display
 Humanization/germlining and formatting of antibodies
 Expression and purification of antibodies
 Assay development and validation for efficacy testing, pharmacokinetic and
immunogenicity testing, cross reactivity analysis, biomarker analysis….
 Characterization of antibodies in in vitro assays (FACS, ELISA, Biacore, qPCR, ex vivo
studies….)
 In vivo characterization of antibodies in
o monkeys/pigs/guinea pigs: thrombosis model (Folts), restenosis model, stroke
model
o mouse Xenograft models
 Pharmacokinetics and immunogenicity testing in different species, PK-PD modeling
 Tissue cross reactivity studies
 Toxicology
 CMC/fill and finish
 CTA filing for phase I studies
 PK-PD modeling clinical studies
 Discussion with clinicians and other consultants (KOLs) on clinical development strategy
 Manage outsourcing of activities to CROs
 Writing/reviewing of study plans, protocols, reports, SOPs, grants
 Recruitment/growth and training of the team
 Planning and tracking of progression
 FTE allocation
 Budgeting
 BD discussions/due dilligence
 Project and people management

2. Studies
Bachelor of Chemistry: (October 1987-July 1989: distinction)
Free University of Brussels
Licentiate in Chemistry: (October 1989-July 1991: distinction)
Catholic University of Leuven, Prof. Dr. Y. Engelborghs
Ph.D. in Science: (September 1991-December 1995)
Catholic University of Leuven, Gasthuisberg, Center for Molecular and Vascular Biology,
Prof. Dr. D. Collen, Prof. Dr. H.R. Lijnen
Title thesis: Mechanism of the interaction between plasmin(ogen), 2-antiplasmin and
staphylokinase. I did the full preclinical characterization of staphylokinase and was involved
in the enrolment of the first patients.
Title of joint thesis: “Phage Display” a useful technique to produce more active enzymes
Work experience
September 2009- December 2015: arGEN-X: research fellow: initiated the companies lead
project (ARGX-110) six years ago and took it from pre-clinical to clinical studies as project
manager. Currently responsible for PK-PD modeling and clinical operations. ARGX-110 is an
anti-CD70 monoclonal antibody with ADCC enhanced properties, currently in phase I studies
in cancer patients. Project manager for Fn14, another autoimmune and cancer target.
Involved in partnering discussions, due dilligence and responsible for all academic
collaborations.
August 2008- June 2009: Tibotec-Virco, Johnson&Johnson, Generaal de Wittelaan,
Mechelen, Belgium: Associate director Virology lab operations. Responsible/supervision of
the diagnostics labs in Virco.
December 2001-July 2008: Ablynx, Technologiepark 4, 9052 Zwijnaarde, Belgium:
associate director pharmacology. I was heavily involved in the start up of the company
Ablynx. My initial role in the company was to manage the development and characterization
of Nanobodies against some potentially interesting clinical targets. One of these targets was
von Willebrand factor. I managed this program from the research phase till development-
early clinical phase. In February 2007 I was promoted to associate director pharmacology. I
was heading a group of 24 technicians and 11 (senior) scientists in the pharmacology
department. My department was responsible for PK-PD studies (animal-human), toxicity
studies, development and transfer of assays for clinical studies to CROs, animal efficacy
models, tissue cross reactivity testing….
September 1997-November 2001: Department of Immunology, Parasitology and
Ultrastructure, Free University of Brussels, VIB: post-doc. I was responsible for different
projects regarding Nanobodies and supervising 2 technicians. I was actively involved in the
start-up of a spin-off company (Ablynx) where I was the first employee

3. February 1996-June 1996: Centre for Human Genetics, Prof. J.J. Cassiman, Gasthuisberg,
Leuven
June 1996-August 1997: University Fertility Center, Gasthuisberg, Leuven
Values-strengths
 I value a good team spirit: we work on a project as a team and will jointly do
everything possible to bring it to a good end and this within the timelines
 The results from the team I am responsible for should be of excellent quality
 I am enthusiastic, very efficient and motivated
 I value good communication and sharing of information to the whole team
 Training of people, explaining the goals of the project and decisions taken by senior
management is very important to get the best out of them
Publications
1. Silence K., D’Hoore A., Engelborghs Y. Fluorescence stopped-flow study of the
interaction of tubulin with the antimitotic drug MDL 27048. Biochemistry 1992; 31:
11133-11137.
2. Collen D., Silence K., Demarsin E., De Mol M., Lijnen H.R. Isolation and
characterization of natural and recombinant staphylokinase. Fibrinolysis 1992; 6:
203-213.
3. Ueshima S., Silence K., Collen D., Lijnen H.R. Molecular conversions of recombinant
staphylokinase during plasminogen activation in purified systems and in human
plasma. Thrombosis and Haemostasis 1993; 70: 495-499.
4. Silence K., Collen D., Lijnen H.R. Interaction between staphylokinase, plasmin(ogen)
2-antiplasmin. Recycling of staphylokinase after neutralization of the plasmin-
STAR complex by 2-antiplasmin. The Journal of Biological Chemistry 1993; 268:
9811-9816.
5. Silence K., Collen D., Lijnen H.R. Regulation by 2-antiplasmin and fibrin of the
activation of plasminogen with recombinant staphylokinase in plasma. Blood 1993;
82: 1175-1183.
6. Silence K., Hartmann M., Gührs K.H., Gase A., Schlott B., Collen D., Lijnen H.R.
Structure-function relationships in staphylokinase as revealed by “clustered charge-
to-alanine” mutagenesis. The Journal of Biological Chemistry 1995; 270: 27192-
27198.
7. Collen D., Bernaerts R., Declerck P., De Cock F., Demarsin E., Jenné S., Laroche Y.,
Lijnen H.R., Silence K., Verstreken M. Recombinant staphylokinase variants with
altered immunoreactivity. I. Construction and characterization. Circulation 1996; 94:
197-206.
8. Lijnen H.R., Silence K., Hartmann M., Gührs K.H., Gase A., Schlott B., Collen D.
Fibrinolytic properties of staphylokinase mutants obtained by “clustered charge-to-
alanine” mutagenesis. Fibrinolysis 1996; 10: 177-182.

4. 9. De Genst E., Silence K., Ghahroudi MA., Decanniere K., Loris R., Kinne J., Wyns L.,
Muyldermans S. Strong in vivo maturation compensates for structurally restricted H3
loops in antibody repertoires. The Journal Biological Chemistry 2005; 280: 14114-
14121.
10. Hulstein JJ., de Groot PG, Silence K., Veyradier A., Fijnheer R., Lenting PJ., A novel
nanobody that detects the gain of function phenotype of von Willebrand factor in
ADAMTS13 deficiency and von Willebrand disease type 2B. Blood 2005: 106: 3035-
3042.
11. De Genst E., Silence K., Decanniere K., Conrath K., Loris R., Kinne J., Muyldermans
S., Wyns L. Molecular basis for the preferential cleft recognition by dromedary heavy-
chain antibodies. Proc Natl Acad Sci USA 2006: 103: 4586-4591.
12. Hulstein JJ., van Runnard Heimel PJ., Franx A., Lenting PJ., Bruinse HW., Silence
K., de Groot PG., Fijnheer R. Acute activation of the endothelium results in increased
levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low
platelets (HELLP) syndrome. J Thromb Haemost. 2006: 4:2569-2575.
13. Coppieters K., Dreier T., Silence .K, de Haard H., Lauwereys M., Casteels P.,
Beirnaert E., Jonckheere H., Van de Wiele C., Staelens L., Hostens J., Revets H.,
Remaut E., Elewaut D., Rottiers P. Formatted anti-tumor necrosis factor alpha VHH
proteins derived from camelids show superior potency and targeting to inflamed joints
in a murine model of collagen-induced arthritis.Arthritis Rheum. 2006: 54:1856-1866.
14. Ulrichts H, Silence K, Schoolmeester A, de Jaegere P, Rossenu S, Roodt J, Priem
S, Lauwereys M, Casteels P, Van Bockstaele F, Verschueren K, Stanssens P,
Baumeister J, Holz JB. Antithrombotic drug candidate ALX-0081 shows superior
preclinical efficacy and safety compared with currently marketed antiplatelet drugs.
Blood. 2011: 118:757-765.
15. Silence K, Dreier T, Moshir M, Ulrichts P, Gabriels SM, Saunders M, Wajant H,
Brouckaert P, Huyghe L, Van Hauwermeiren T, Thibault A, De Haard HJ. ARGX-110,
a highly potent antibody targeting CD70, eliminates tumors via both enhanced ADCC
and immune checkpoint blockade. MAbs. 2014:523-532.
16. Trebing J, El-Mesery M, Schäfer V, Weisenberger D, Siegmund D, Silence K,
Wajant H. CD70-restricted specific activation of TRAILR1 or TRAILR2 using scFv-
targeted TRAIL mutants. Cell Death Dis. 2014: 30-35
17. Trebing J, Lang I, Chopra M, Salzmann S, Moshir M, Silence K, Riedel SS,
Siegmund D, Beilhack A, Otto C, Wajant H. A novel llama antibody targeting Fn14
exhibits anti-metastatic activity in vivo. MAbs. 2014: 297-308.
18. Jacobs J, Zwaenepoel K, Rolfo C, Van den Bossche J, Deben C, Silence K,
Hermans C, Smits E, Van Schil P, Lardon F, Deschoolmeester V, Pauwels P.
Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small
cell lung cancer. Oncotarget. 2015: 6:13462-75.
19. Hultberg A, Morello V, Huyghe L, De Jonge N, Blanchetot C, Hanssens V, De Boeck
G, Silence K, Festjens E, Heukers R, Roux B, Lamballe F, Ginestier C, Charafe-
Jauffret E, Maina F, Brouckaert P, Saunders M, Thibault A, Dreier T, de Haard H,
Michieli P. Depleting MET-Expressing Tumor Cells by ADCC Provides a Therapeutic
Advantage over Inhibiting HGF/MET Signaling. Cancer Res. 2015:;75:3373-83.