Dear fellow shareholder,

17 Posts
flosz
23
Dear fellow shareholder,

Crucell is a rapidly growing biopharmaceutical company with ambitious goals. We aim to create shareholder value by following a clear and convincing strategy for growth.
The progress we have made in 2007 is a clear indication that we are executing on this strategy. Growth is the major theme underlying all our accomplishments; our sales increased by more than 50% compared to 2006. We are selling our products on a global basis using our own distribution network. And we are active in many countries in product and technology development, clinical studies and vaccine production.
Our strong autonomous growth in 2007 was driven by the successful roll-out of Quinvaxem™ in the fourth quarter of 2006, the only fully-liquid pentavalent vaccine that protects against five potentially deadly childhood diseases in one shot. The product makes a significant contribution to children’s vaccination programs in the developing world and is Crucell’s best selling product. Quinvaxem™ has enabled the company to become a major supplier to paediatric vaccination programs worldwide. The significant growth Quinvaxem™ showed in 2007 is expected to continue in 2008.
The rapid pace of our growth is also reflected in the progress of clinical trials, including our rabies monoclonal antibodies, the FluCell development by sanofi pasteur and our progress in tuberculosis trials.
The scalability of our PER.C6® technology had already demonstrated levels of up to 20,000 liters per bio fermentation unit.
Another important milestone was achieved with the PER.C6® technology for the production of monoclonal antibodies and recombinant proteins. Scientists reached a record level titer of 15 g/L at harvest for an antibody product. It demonstrates the power and robustness of the PER.C6® technology and shows the impact it will have to the overall economics of manufacturing biopharmaceuticals.
As Crucell’s Management, we must now rise to the challenge of maintaining the forward momentum and further stimulating the Company’s powers of innovation while at the same time managing available production facilities at optimal capacity and focusing on efficient operations.
We intend to use the expansion into new markets and the sales and marketing potential of the Company as an important driver for future growth. We will strive to have ‘best in class’ marketing and sales capabilities. This approach will allow us to operate quickly and effectively on the international commercial markets.
“As Crucell’s Management, we must now rise to the challenge of maintaining the forward momentum and further stimulating the Company’s powers of innovation while at the same time managing available production facilities at optimal capacity and focusing on efficient operations.”
We are the largest independent player in the vaccine business based on revenue, with sales and other income in 60 countries totalling €213.1 million in 2007.
We generated positive cash flow driven by a strong operating cash flow of €22.2m in 2007 compared to a negative €54.0m in 2006.
As we grow further, capturing synergies and rationalization becomes ever more important. Therefore we have nominated Dr. Cees de Jong to join our Management Board. This nomination will be proposed to Crucell’s shareholders at the company’s AGM on May 30, 2008. Cees joined Crucell as Chief Operating Officer in September 2007 and with his focus on operational excellence, he is an integral part of Crucell’s strategy to accelerate growth. A rigorous review of Crucell’s business processes worldwide is currently being conducted and savings of approximately 15% by the end of 2009 are being targeted.
Our Company’s future looks promising, supported by our solid financial position. What we have achieved so far has been feasible due to the efforts and motivation of our employees, which are the Company’s major asset, and to your willingness as shareholders to invest in Crucell, which makes it possible to realize our ambitious goals. We thank you for your continuous support.
Ronald H.P. Brus
President and Chief Executive Officer
Leiden, the Netherlands, May 1, 2008
www.crucell.com/Annual_Report_2007/ov...
flosz
9
Healthy Ambition
As a result of the acquisitions of Berna Biotech, Berna Products Corporation and SBL Vaccines in 2006, our operations expanded considerably. Our workforce grew from just under 300 to well over 1,000 employees and the number of worldwide locations where we operate increased five-fold – an increase in the scale, scope and complexity of the company.
Having integrated these new businesses, it is now appropriate to look at opportunities to improve our operational excellence – an integral part of our strategy for accelerating growth. Our Healthy Ambition program, which includes a rigorous review of our business processes around the world, includes a target to find savings of approximately 15% on the 2007 cost base, excluding research and development.
Three triggers for operational excellence
The growth in workforce, locations and complexity triggers three potential drivers for operational excellence,
• Capturing synergies relating to both costs and resources.
• Reducing costs to create a competitive cost position.
• Funding growth, by creating cash to fund our biotech pipeline.
“Targeting annual savings of 15% (excluding R&D) by the end of 2009.”
Phases of the program
Healthy Ambition started in January 2008, and consists of three initial phases prior to being rolled out in the second half of our 2008 financial year. Accordingly, while there will be some savings coming through during the second half of 2008, the bulk of the savings will not be realized until 2009.
Healthy Ambition: preliminary findings
• A detailed analysis of our procurement processes and spending found that our spendbase is fragmented and therefore under-leveraged. As a result, there is significant potential for cost reduction.
• Additionally, we have assessed our true ‘cost-to-serve’. We have found that complexity in our product portfolio is a major cost driver. Again, this suggests there is considerable potential to reduce costs.
• Finally, we have started looking into our business processes. We believe there are opportunities to improve the alignment of, and to centralize, some functions.
www.crucell.com/Annual_Report_2007/op...
k61
0
[quote=flosz]
Healthy Ambition
As a result of the acquisitions of Berna Biotech, Berna Products Corporation and SBL Vaccines in 2006, our operations expanded considerably. Our workforce grew from just under 300 to well over 1,000 employees and the number of worldwide locations where we operate increased five-fold – an increase in the scale, scope and complexity of the company.
Having integrated these new businesses, it is now appropriate to look at opportunities to improve our operational excellence – an integral part of our strategy for accelerating growth. Our Healthy Ambition program, which includes a rigorous review of our business processes around the world, includes a target to find savings of approximately 15% on the 2007 cost base, excluding research and development.
Three triggers for operational excellence
The growth in workforce, locations and complexity triggers three potential drivers for operational excellence,
• Capturing synergies relating to both costs and resources.
• Reducing costs to create a competitive cost position.
• Funding growth, by creating cash to fund our biotech pipeline.
“Targeting annual savings of 15% (excluding R&D) by the end of 2009.”
Phases of the program
Healthy Ambition started in January 2008, and consists of three initial phases prior to being rolled out in the second half of our 2008 financial year. Accordingly, while there will be some savings coming through during the second half of 2008, the bulk of the savings will not be realized until 2009.
Healthy Ambition: preliminary findings
• A detailed analysis of our procurement processes and spending found that our spendbase is fragmented and therefore under-leveraged. As a result, there is significant potential for cost reduction.
• Additionally, we have assessed our true ‘cost-to-serve’. We have found that complexity in our product portfolio is a major cost driver. Again, this suggests there is considerable potential to reduce costs.
• Finally, we have started looking into our business processes. We believe there are opportunities to improve the alignment of, and to centralize, some functions.
www.crucell.com/Annual_Report_2007/op...

Heeft onze (vriend)Mark Clrark van ING nog niet gelezen zeker??
flosz
6
Technologies
5 Core Technologies
• PER.C6®
• AdVac®
• MAbstract®
• STAR® (StarTAR)
• Virosome

What is PER.C6®?
PER.C6® is a human designer cell line for the development and large-scale manufacturing of biopharma products. In areas where we do not aim to develop our own products, we license the technology to the biopharmaceutical industry. Currently over 60 companies and organizations have selected our PER.C6® technology to develop their own products across a wide range of therapeutic areas.
PER.C6®: adaptable
PER.C6®: well protected
Our PER.C6® technology is protected by numerous patents. In addition, in order to benefit from our proprietary technology, potential customers not only need our know-how, but also our PER.C6® cells, which are only available from us under agreement. These agreements put certain restrictions on further dissemination and use of the PER.C6® cells. This combination of protections – patented know-how and the need to have access to the actual PER.C6® cells results in the PER.C6® technology being the best protected human cell technology in the world.
PER.C6® for protein and antibody production
We have a collaboration with DSM Biologics for the application of PER.C6® for proteins and antibodies. Together with DSM we license PER.C6® for proteins and antibodies as well as invest in further innovation of PER.C6®.
Working alongside DSM Biologics on the PER.C6® manufacturing platform, we believe that there is further potential to reduce the production costs of monoclonal antibodies, whilst increasing yield resulting in more affordable treatments for patients.
In March 2008, we jointly announced that we had achieved a record level titer of 15 grams per liter at harvest for an antibody product using PER.C6® at our PERCIVIA joint venture development center in Massachusetts, U.S.
www.crucell.com/Annual_Report_2007/ou...
Any manufacture of biopharmaceuticals has to take account of rapidly changing factors, such as rising volume demands and more stringent safety requirements. These shifts are a major challenge to conventional manufacturing platforms that have not adapted or become sufficiently flexible to cope with such changes. Our PER.C6® production cell line, however, is designed to meet these demands.
Our strong product portfolio is supported through a range of patented technologies. Our cutting-edge technology platforms enable the discovery, development and production of vaccines, therapeutic proteins and gene therapy products.
Our other core technologies:
AdVac® Technology, used in combination with PER.C6®, to develop recombinant vaccines
MAbstract® Applied for discovery of novel drug targets and identification of human antibodies
STAR® Designed to enhance production yields of recombinant human antibodies and proteins on mammalian cell lines
Virosome A vehicle enabling the use of virus antigens in the making of vaccinations



www.crucell.com/Annual_Report_2007/ou...
www.crucell.com/Annual_Report_2007/ou...
www.crucell.com/Annual_Report_2007/ou...
www.crucell.com/Annual_Report_2007/ou...
Bijlage:
flosz
2
The Annual General Meeting of Shareholders (AGM) of Crucell N.V. will be held on Friday, 30 May 2008 at 14:00 CET, at the Hooglandse kerk, Middelweg 2, 2312 KH Leiden, The Netherlands.

AGENDA
van de Jaarlijkse Algemene Vergadering van Aandeelhouders 2008 van
CRUCELL N.V. (de "Vennootschap")
op vrijdag 30 mei 2008 om 14.00 uur.
Hooglandse kerk, Middelweg 2, 2312 KH. Leiden

1. Opening van de vergadering door de Voorzitter van de Raad van Commissarissen.

2. Verslag van de Raad van Bestuur met betrekking tot de stand van zaken en de jaarrekening over het boekjaar 2007 dat is geëindigd op 31 december 2007.

3. a) Voorstel tot handhaving van het gebruik van de Engelse taal in de jaarrekening van de Vennootschap. (Besluit)
b) Voorstel tot vaststelling van de jaarrekening over het boekjaar 2007 dat is geëindigd op 31 december 2007. (Besluit)

4. Reserverings- en dividendbeleid.

5. a) Voorstel tot verlening van kwijting aan de leden van de Raad van Bestuur voor het gevoerde bestuur, voor zover zulks blijkt uit de financiële verslaggeving. (Besluit)

b) Voorstel tot verlening van kwijting aan de leden van de Raad van Commissarissen voor hun toezicht op het gevoerde bestuur, voor zover zulks blijkt uit de financiële verslaggeving. (Besluit)

6. Voorstel tot herbenoeming van Deloitte Accountants B.V. als externe accountant van de Vennootschap. (Besluit)

7. Aftreden van de heer Dominik Koechlin als lid van de Raad van Commissarissen en voorstel tot verlening tot kwijting. (Besluit)

8. Voorstel tot benoeming van de heer Steve Davis als lid van de Raad van Commissarissen per heden, zulks overeenkomstig de voordracht opgemaakt door de Raad van Commissarissen. (Besluit)

9. a) Voorstel tot herbenoeming van Ronald Brus als lid van de Raad van Bestuur, voor een termijn van vier (4) jaar, zulks overeenkomstig de voordracht opgemaakt door de Raad van Commissarissen. (Besluit)
b) Voorstel tot herbenoeming van Leonard Kruimer als lid van de Raad van Bestuur, voor een termijn van vier (4) jaar, zulks overeenkomstig de voordracht opgemaakt door de Raad van Commissarissen. (Besluit)
c) Voorstel tot herbenoeming van Jaap Goudsmit als lid van de Raad van Bestuur, voor een termijn van vier (4) jaar, zulks overeenkomstig de voordracht opgemaakt door de Raad van Commissarissen. (Besluit)
d) Voorstel tot benoeming van Cees de Jong als lid van de Raad van Bestuur, voor een termijn van vier (4) jaar, zulks overeenkomstig de voordracht opgemaakt door de Raad van Commissarissen. (Besluit)

10. Voorstel tot vaststelling van de beloning van iedere commissaris en voorstel tot goedkeuring van de op aandelen gebaseerde beloning voor de Raad van Commissarissen. (Besluit)

11. a) Voorstel tot goedkeuring van beloningsbeleid voor de Raad van Bestuur. (Besluit)

b) Voorstel tot goedkeuring van optieregeling voor leden van de Raad van Bestuur. (Besluit)

12. Voorstel om aan de Raad van Bestuur de bevoegdheid te verlenen tot inkoop van eigen aandelen in het kapitaal van de Vennootschap voor een periode van achttien maanden (tot 30 november 2009). (Besluit)

13. a) Voorstel tot verlenging van de periode waarin de Raad van Bestuur bevoegd is tot uitgifte van aandelen en tot het verlenen van rechten tot het nemen van aandelen. (Besluit)

b) Voorstel tot verlenging van de periode waarin de Raad van Bestuur bevoegd is tot beperking of uitsluiting van het voorkeursrecht bij uitgifte van aandelen. (Besluit)

14. Voorstel tot statutenwijziging in verband met moderne communicatie middelen. (Besluit)

15. Rondvraag.

16. Sluiting.
www.crucell.com/page/downloads/FINAL-...
Toelichting:
www.crucell.com/page/downloads/AMCO-_...

VOORSTEL TOT STATUTENWIJZIGING
Crucell N.V.,
gevestigd te Leiden.
Concept d.d. 16 april 2008.
Uitsluitend voor interne discussiedoeleinden.
www.crucell.com/page/downloads/FINAL-...
aossa
5
From IV board

Dear Perseazes,
Thank you for another outstanding compilation of pertinent corporate information. I have forwarded your posting to several friends who have expressed an interest in the stock. I've sent it as well to my wife, to whom I never seem to be able to convey an understandable explanation of the future prospects for CRXL and why we are so heavily invested in it.
flosz
4
Hepavax-Gene

Hepavax-Gene is a Hansenula polymorpha-based recombinant hepatitis B vaccine. Since its launch in 1996, more than
590 million doses of Hepavax-Gene have been commercially distributed in more than 90 countries, making it the third
most used hepatitis B vaccine in the world. A key competitive advantage for Hepavax-Gene is our stable and efficient
production system. The vaccine is produced in Korea.
Hepatitis B (‘HBV’) is a viral infection of the liver that causes various complications if left untreated and may even
ultimately cause death. Transmission of HBV occurs as a result of the exchange of blood, the exchange of fluids during
sexual intercourse, and the exchange of body fluids between an infected mother and a new-born baby during birth.
Market researcher Datamonitor assesses the HBV drugs market at $ 431 million in 2006 across seven major markets and
expects the market to nearly triple in size by 2016. Data monitor predicts rapid growth until 2011 that will slow down in the
following years as a result of the introduction of generics and the impact of routine HBV vaccination.
The key participants in the HBV market for the developed world are GSK and Merck & Co. Main competitors for sales to
supranational organizations are LG, Shanta and SII.
flosz
3
Patents
At December 31, 2007 we owned or co-owned 539 granted patents in the EU territory, 75 patents in the U.S. and 239
patents in the rest of the world.
The following is a summary of the intellectual property rights related to our major products and product developments.

Epaxal and Inflexal V.
Epaxal and Inflexal V are the two virosomal products which are protected by the patent family ‘Immunostimulating and immunopotentiating reconstituted influenza virosomes and vaccines containing them’, which will expire in 2012. In addition, the hepatitis A strain used to produce Epaxal is claimed in a patent family which will expire in 2012.

Hepavax-Gene
The active substance of this monovalent recombinant hepatitis B vaccine is HbsAg which is no longer protected by patent in Europe and most countries in the rest of the world. The Supplementary Protection Certificates with respect to Hepavax-Gene are still valid in Sweden, Italy, and France. However, we are not currently considering Western European
countries for product registration and marketing. The production technology is based on our proprietary Hansenula polymorpha expression technology.

Quinvaxem
We have no patent protection for the active substances of Quinvaxem.

Vivotif
We have no patent protection for the active substances of Vivotif.

Dukoral
We have no patent protection for the active substances in Dukoral, but certain aspects of manufacturing are subject to patent.

We seek patent protection, whenever possible, commercially feasible and appropriate, in respect of any technology or product development that is important to our business. Together with our affiliates in Switzerland, Sweden, Italy and Korea, we have several platform technologies and consequently our intellectual property activities concentrate on protecting these technologies and any improvements thereof in the main worldwide vaccine markets of Europe, the U.S., Canada, Japan and Australia. However, because some vaccine markets are outside these countries, we have also sought protection in other countries, such as Korea, India and China. The IP portfolio is constantly reviewed to decide on maintenance of individual patents or patent families
considering parameters such as actual product performance, product development, patent term, options for commercialization or out-licensing of non-core IP. Our IP tasks are coordinated, patents are filed on a worldwide basis by specialized patent attorneys.
Our patent-related activities do not afford complete protection to our intellectual property rights. Patents in the biotechnology and biopharmaceutical fields involve complex factual and legal questions. Patents may not be issued in respect of our pending applications or in respect of future applications that we file. In addition, a patent that is issued to us
may be narrower than our application or found to be invalid. Others may make attempts to copy, reverse engineer or design around aspects of our technology, or to obtain and use information that we regard as proprietary. Our patent filings may be subject to challenges.

Patent enforcement and proceedings
We may need to litigate or institute administrative proceedings such as oppositions to a patent to enforce or uphold our intellectual property rights or determine the validity and scope of the proprietary rights of others. Likewise, from time to
time it may be necessary to defend our patents in litigation or administrative patent proceedings such as opposition proceedings. We believe that litigation can play a significant role in defining and protecting our intellectual property rights.
We are aware, however, that legal and administrative proceedings can be costly and time-consuming, and result in a diversion of resources. As an alternative to litigation, we may enter into licensing, including cross-licensing, arrangements as a means of clarifying the status of our intellectual property rights.

In 2005, Probiogen, CEVEC Pharmaceuticals and Serono each individually filed oppositions before the European Patent Office against one or more of our PER.C6 patents. All PER.C6 technology patents were upheld after first instance opposition proceedings.
Cell Genesys has filed opposition against our European patent related to our AdVac technology. The opposition is still pending before the opposition division.
In 2005 we lodged opposition against a European patent held by Chiron related to certain aspects of the production of influenza viruses in cell culture; the opposition is still pending.
Our subsidiary Berna Biotech Korea Corporation (formerly Green Cross Vaccine Corporation) and our partner Novartis (formerly Chiron) lodged oppositions against a patent of GlaxoSmithKline (GSK) in Korea. The patent relates to multivalent vaccine formulations, such as our pentavalent vaccine Quinvaxem. In response to the opposition, the patent was revoked by the Korean Intellectual Property Office in December 2004 on the grounds that the subject-matter claimed
in the patent lacks novelty. GSK appealed that decision to the Korean Patent Court. After a hearing which took place in April, 2006, the Korean Patent court dismissed the appeal in June, 2006. GSK has appealed this decision. If the Korean Supreme Court were to reverse the decision of the Patent Court and if GSK were to enforce its patent, Berna Biotech
Korea Corp. could be found to have infringed the patent. In this case, we may be forced to delay or even cancel our commercial activities with this vaccine. As a consequence, we would lose revenue and our business would be adversely affected.
In addition, production of Quinvaxem requires a particular vaccine component that may become the subject of a patent dispute between either GSK and us or GSK and our supplier of that component. The patent on that particular component, held by GSK, is currently under opposition before the patent office and a definitive outcome on the validity of the patent is
expected to take a number of years. A negative outcome of this opposition proceeding could lead to infringement proceedings between GSK and us or GSK and our supplier, although we believe that neither we nor our supplier would be held to have infringed or be infringing that patent. The outcome of legal disputes is invariably difficult to predict with accuracy, but in the event GSK were to prevail in infringement proceedings against us, this would adversely affect our business.

flosz
3
Vervolg.

In addition to protecting our intellectual property rights, our commercial success also depends on our ability to operate without infringing the intellectual property rights of others. We monitor patent applications to the extent available, patents
issued and publications of discoveries in scientific or patent literature to keep abreast of the activities of others in our field and, with the assistance of our internal and external patent counsel and other external advisors, assess whether our activities or products infringe the patents or proprietary rights of third parties. A number of third parties have been granted
patents that cover technologies related to ours and similar patents may be granted in the future. We believe that our current activities do not infringe any valid claims of patents or any other proprietary rights of third parties. We will consider the intellectual property rights of others as we continue to identify and develop potential products and may have to enter
into licensing or other agreements or use alternative technologies.
Research has been conducted for many years in the fields of biotechnology and biopharmaceuticals. This has resulted in a substantial number of issued patents and an even larger number of patent applications. The U.S. Patent Office maintains patent applications that are filed only in the U.S. in secrecy until patents issue, and publication of patent applications elsewhere and of discoveries in the scientific or patent literature frequently occurs substantially later than the
date of the underlying discoveries. Moreover, patents that appear not to affect our activities may be construed broadly. As such, we or our licensees may be found to infringe the patents or violate other proprietary rights of third parties and may
be enjoined from pursuing research, development or commercialization of our or their products or be required to pay damages. In these circumstances, licensing or other arrangements for addressing these infringements or violations may not be available, or may not be available on commercially acceptable terms.

Technology licenses from third parties
We licensed numerous technology and patents for specific use as part of our technology platforms from a number of third parties.
We entered into a technology license agreement with Xoma in the field of bacterial expression technology. This license allows us to develop diagnostic and therapeutic antibodies in the field of infectious disease using phage-display technology. The agreement provides us with options to expand the license to cover additional disease fields. Under the
terms of the agreement, we pay Xoma milestone payments and royalties on products as and when developed and marketed using the licensed technology.
We also hold a license under the phage antibody display patent portfolio owned or controlled by MedImmune (formerly Cambridge Antibody Technology) and MRC, a cross-license with Transgene S.A. under which we granted to Transgene a non-exclusive PER.C6 license for the manufacture and sale of certain types of vectors for use in gene therapy, and a
license to phage antibody-display technology and part human, or chimeric, binding proteins and molecules from Enzon Corporation’s subsidiary, SCA Ventures, Inc.
In the field of vaccines, we have concluded an agreement with the Rockefeller University in New York. According to the agreement, we have the exclusive rights to use and exploit the Rockefeller patents related to ex vivo and in vivo targeting of dendritic cells with the use of viral vectors.
The Company has licensed adjuvation technology called ISCOMS from Isconova AB for the development, manufacture and commercialisation of improved influenza vaccines.
When licensing our technology to third parties we seek to obtain access to any improvement patents via so-called grant-back provisions to reduce the risk of being exempted from using such improvements for our own benefit, or that of our licensees.
Technology licenses to third parties We have issued certain licenses on an exclusive basis. These licenses generally state that we will not provide the
licensed technology to a party other than the exclusive licensee for use in the area covered by the exclusive license. These licenses also generally provide for higher payments.
************************
Btw...josti al een poosje niet gezien...heerlijk zonnig plekje aan z.z.zee?
flosz
2
Property, plant and equipment

Our corporate offices and research activities are located in facilities of approximately 8.700 square meters in Leiden, the Netherlands. The section of this building that we use in Leiden includes 3.500 square meters of laboratories, with BioSafety Level (BSL) 1, BSL 2 and BSL 3 labs. The remainder of the main building is divided into 2,800 square meters of office space and 2,400 square meters for storage, technical areas, washrooms, waste destruction and sterilization.
In addition, we lease 1200 square meters of space adjacent to the corporate main building. In 2007 we closed our pilot plant and production facility, which was located in a separate building in the Leiden BioScience Park.

In 2005, we began to construct a new GMP Process Technology Center of 5.400 square meters in Leiden. This new facility will be a BioSafety Level (BSL) 3 facility, in which two concurrent products can be produced, on either BSL 2 and/or BSL 3 safety level. The building will consist of 1,500 square meters of production space; 220 square meters of quality control labs; 185 square meters BSL 3 research and development labs; 80 square meters filling (up to 2,000 ampoules); 40 square meters of buffer and medium preparation; 310 square meters of offices; 350 square meters of
storage and 2,715 square meters for utilities, washing area, waste destruction and sterilization and technical areas.
The new centre is named after Crucell co-founder Dinko Valerio, and is known as PTC Valerio Building. The PTC Valerio Building will give us the in-house capability to support vaccine, protein and monoclonal antibody process design and development, minimizing requirements for outsourcing. Bioreactors of 2, 10, 30 and 100-liter capacities have already been
constructed off-site and are installed. There is also room for expansion, with multiple 100-liter wave-bags, disposable stirred tank bioreactors, and large scale down stream processing equipment and scale-up of fill and finish capacity.
When fully operational, the Valerio Building will meet the highest environmental and safety standards recommended for the laboratory activities to be conducted there. The facility must receive approval from the Dutch government to produce material for use in humans. Extensive precautions will be taken to ensure safety and continuity of operations. Product
quality will be strictly monitored, maintained and administered in-house.
===========================================
The facility is currently scheduled to become operational in the first half of 2008.
===========================================

Since our 2006 acquisitions, we also have office space, laboratories, production facilities, pre-clinical facilities and storage space in Switzerland, Spain, Germany, Sweden and Korea.
The following table sets out information regarding our main facilities outside the Netherlands:

Bern, Switzerland
(two locations)
Research and development
(including pre-clinical facilities)
8,618 m2 and production facilities
(12,427 m2); office space
(5,635 m2) and storage
buildings (15,988 m2) (owned)

Madrid, Spain
Production facilities
(1600 m2), storage buildings
(2400 m2) and office space/labs
(1409 m2) (owned)

Seoul, Korea
Development and
production facilities
(2,201 m2), pre-clinical facilities
(999 m2), storage facilities
(1,305 m2), office space
(1,819 m2) (leased until 2010)

Stockholm, Sweden
Development and
production facilities
(4,866 m2), pre-clinical facilities
(1606 m2), storage facilities
(5,990 m2), office space
(2,662 m2) (leased until 2020)

Our manufacturing facilities in Switzerland are FDA/EMEA-approved and are used primarily for the production of Inflexal V, Vivotif, Epaxal and mammalian cell culture-based products. One of our facilities also includes facilities for lyophilization and a Center of Mammalian Cell Culture, which is currently not in use.

Our manufacturing facilities in Korea are World Health Organization-approved and are used primarily for the production of Quinvaxem and Hepavax-Gene and for formulating and filling vials. The manufacturing process used at our Korean facilities are based on the patented Hansenula polymorpha yeast expression technology.

In Spain, the center of our European filling and packaging operations, we operate a filling line for syringes.

In Sweden, our manufacturing facilities are EMEA/WHO-approved and are used for the production of Dukoral and the recombinant protein rCTB.

In 2007 € 27,156 was invested in property, plant and equipment compared to € 20,337 in 2006. The investments in 2007 mainly related to our new GMP production facility in Leiden, the Netherlands and investments in our facilities in Bern, Switzerland that will improve current production processes and allow in-house production of materials currently acquired from third parties.
In 2006 € 20,337 was invested in property, plant and equipment compared to € 17,137 in 2005. Investments were mainly related to building and equipping our new GMP production facility in Leiden, the Netherlands.
flosz
3
Overview licensees and partners
Per year-end 2007 we have the following licensees and partners, (WOW-YEAH BABY YEAH):

Vaccines Partner/licensee
Starting date/ Technology/ Disease target/ Development stage
Acambis Nov. 2007 PER.C6 HSV Pre-clinical
ADImmune Corp. Oct. 2006 PER.C6 Japanese Encephalitis Pre-clinical
Aeras Global TB Vaccine Foundation Mar. 2004 PER.C6 and AdVac Tuberculosis Phase 1
Bestewil Holding BV Jan. 2006 Co-micelles Influenza Pre-clinical
Harvard School of Medicine Dec. 2003 AdVac + Ad5HVR48 HIV Pre-clinical
International AIDS Vaccine Initiative (IAVI) Sep. 2004 AdVac HIV Phase 1
Kimron Veterinary Institute Jul. 2003 PER.C6 West Nile virus—Veterinary vaccine (avian) Marketed in Israel
Merck & Co. Inc. Oct. 2005 PER.C6 Hepatitis C Pre-clinical
Merck & Co Inc. Dec 2006 Ad5HVR48 HIV Pre-clinical
National Institutes of Health (NIH) Mar. 2002 PER.C6 and AdVac Ebola, Lassa and Marburg Phase 1
National Institutes of Health (NIH) Mar. 2004 PER.C6 and AdVac Malaria Phase 1
Neotropix Mar. 2004 PER.C6 Oncology Phase 1
Novartis Dec. 2004 PER.C6 Alphavirus Pre-clinical
Pfizer animal health Mar. 2007 PER.C6 Veterinary Pre-clinical
Sanofi pasteur Dec. 2003 PER.C6 Influenza Phase 2
Singvax Mar. 2005 PER.C6 Japanese Encephalitis Pre-clinical
Tibotec Pharmaceuticals Limited Nov. 2005 PER.C6 Undisclosed vaccine Pre-clinical
Transgene SA Dec. 2007 PER.C6 Undisclosed vaccine Pre-clinical
Vaxin, Inc. Sep. 2004 PER.C6 Respiratory viruses Phase 1
Wyeth Pharmaceuticals Jul. 2007 AdVac Non-disclosed Pre-clinical

Proteins
Partner/licensee Starting date Technology Disease target Development stage
Abbott Jan. 2007 STAR Portfolio antibodies Pre-clinical
Biotecnol SA Jan. 2007 PER.C6 Portfolio antibodies Pre-clinical
Daiichi Sankyo Ltd. Nov. 2007 PER.C6 Portfolio antibodies Pre-clinical
Ferring International Research Center SA May 2005 PER.C6 Women’s healthcare Pre-clinical
Ferring International Research Center SA Dec. 2005 PER.C6 Women’s healthcare Pre-clinical
Genentech Feb. 2004 STAR — —
Genzyme Corporation Dec. 2005 STAR Portfolio proteins Pre-clinical
Invitrogen Corp. Sep. 2007 STAR Monoclonal antibodies Pre-clinical
ISU ABXIS Jan. 2008 PER.C6 Portfolio antibodies Pre-clinical
IQ Corporation Oct. 2005 PER.C6 Anti-anthrax antibody Pre-clinical
LFB Biotechnologies Jul. 2007 PER.C6 Undisclosed antibodies Pre-clinical
Masterclone Jul 2007 PER.C6 Undisclosed antibodies Pre-clinical
Medarex Inc. May 2005 STAR Portfolio antibodies Pre-clinical
Medarex Inc. Dec. 2007 PER.C6 Portfolio antibodies Pre-clinical
MedImmune Oct. 2007 PER.C and MAbstract Anti-bacterial antibodies Pre-clinical
Merck & Co., Inc. May 2003 PER.C6 Portfolio antibodies Pre-clinical
Merus B.V. Jun. 2004 PER.C6 Portfolio oligoclonics Pre-clinical
Micromet AG Nov. 2004 PER.C6 Portfolio antibodies Pre-clinical
MorphoSys AG Sep. 2004 PER.C6 Portfolio antibodies Pre-clinical
Novartis Sep. 2006 STAR Portfolio antibodies, Proteins Pre-clinical
Novartis Aug. 2004 PER.C6 HCV protein Pre-clinical
***Patrys***? Feb. 2007 PER.C6 Portfolio antibodies Pre-clinical
ProFibrix Dec. 2007 PER.C6 Portfolio antibodies Pre-clinical
PR&D Biotech SA (Recepta Biopharma SA) Nov. 2007 PER.C6 Portfolio antibodies Pre-clinical
Sartorius Biotech GmbH Jun. 2007 PER.C6 Portfolio antibodies Pre-clinical
Synergenics/Synco Biopartners Investments B.V. Aug. 2004 PER.C6 Portfolio antibodies Pre-clinical
Taiwanese Development Center for Biotechnology Mar. 2007 PER.C6 Undisclosed proteins Pre-clinical
UCB S.A. Mar. 2006 PER.C6 Portfolio antibodies Pre-clinical
UCB Celltech Sep. 2006 STAR Portfolio antibodies Pre-clinical
UMN Pharma Mar. 2006 PER.C6 Undisclosed protein Pre-clinical
XOMA Ltd Jan. 2006 STAR Portfolio antibodies, Proteins Pre-clinical

Gene therapy
Partner/licensee Starting date Technology Disease target Development stage
Ark Therapeutics Jan. 2006 PER.C6 Portfolio Phase II
GeneMax Corp. / TAP-Immune Aug. 2003 PER.C6 Portfolio Pre-clinical
GenVec Inc. Jul. 2002 PER.C6 Cardiovascular Phase II
Merck & Co., Inc. Nov. 1998 PER.C6 Portfolio Pre-clinical
Merial Ltd. Dec. 2005 PER.C6 Veterinary Pre-clinical
NeoTropix Mar. 2004 PER.C6 Oncology Pre-clinical
Transgene SA Apr. 2001 PER.C6 Portfolio Phase I/II
Vascular Biogenics Ltd Mar. 2005 PER.C6 Portfolio Pre-clinical

Alliances with contract managers for production
Partner/licensee Starting date Technology Area
Cambrex Aug. 2004 PER.C6 Medium development
DSM Biologics Dec. 2002 PER.C6
Therapeutic proteins
(including antibodies)
Gene Medicine Japan, Inc. Oct. 2003 PER.C6
Recombinant vaccines
& gene therapy products (Asia)
Hyclone, Inc. Dec. 2003 PER.C6 Medium development
Invitrogen Corp. Jun. 2003 PER.C6 Medium development
JRH Biosciences Inc. May 2004 PER.C6 Medium development
Molecular Medicine BioServices, Inc. Dec. 2001 PER.C6
Recombinant vaccines
& gene therapy products (U.S.)
Sigma-Aldrich Corp. Dec. 2003 PER.C6 Medium development

Functional Genomics
Partner/licensee Starting date Technology Area
Galapagos Genomics N.V. Jun. 1999 PER.C6 Genomics


Subsidiaries and other equity investments

Pevion Biotech AG
In 2002 Pevion Biotech was founded as joint venture by Berna Biotech and Bachem AG. The company was dedicated to creating novel virosomal formulated vaccines and bringing them from research into clinical development. On November 5, 2007, Crucell sold all of the 2.9 million shares it owned in Pevion Biotech for € 6.1 million to other Pevion Biotech shareholders. Prior to this sale, our ownership interest had already been diluted from 50% in 2006 to 36% in early 2007.
We realized a gain of € 2.2 million on the sale.

Kenta Biotech AG
In 2006, Kenta Biotech AG was founded. Berna Biotech AG contributed investments in kind of € 3.3 million in exchange for shares equal to 36.74% of Kenta Biotech’s share capital. Kenta Biotech AG is focusing on the discovery and development of innovative, fully human monoclonal antibodies for the life-saving treatment of patients with serious infectious diseases.

ADImmune Corp.
In March 2007, we announced that we have completed an influenza alliance with Taiwan-based ADImmune Corporation.
Under the terms of the deal, ADImmune will use our virosome technology to produce a virosomal adjuvanted influenza vaccine for specified markets: Taiwan, Japan and Macau. Additionally, ADImmune will produce influenza antigen, which we may purchase for the production of our vaccine product, Inflexal V. In consideration of the rights and licenses granted in respect of the technology, ADImmune paid an amount of € 8.9 million (TWD 394,887,000). We obtained a 20% equity stake in ADImmune for which we also paid an amount of € 8.9 million.

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2
Vervolg.

Galapagos N.V.
Galapagos N.V. (‘Galapagos’) is a discovery company focused on the rapid identification of disease modifying drug targets through the functional screening of human disease models, and the subsequent progression of these targets into drug discovery. The company is listed on the NYSE Euronext Brussels and NYSE Euronext Amsterdam stock exchanges (ticker symbol: GLPG).
Galapagos holds a royalty free exclusive license to use our PER.C6 technology for conducting activities in the field of functional genomics research. Under the license, Galapagos uses PER.C6 technology in conjunction with Tibotec’s bioinformatics technology to generate adenoviral gene libraries. Tibotec and we have agreed not to compete with the activities of Galapagos, which holds the rights to the products and technology that it develops. The Company owns 5.8% as of December 31, 2007 (2006: 6.2%).

Marketing and sales partners
We have our own sales and marketing infrastructure in our markets in the Netherlands, Switzerland, U.S., Korea, the Nordic region, Italy, Canada, Spain, China, Argentina, Indonesia and Vietnam. This sales and marketing infrastructure includes a dedicated sales force for supranational organizations, to ensure broader market access for our products and
we have established a strong network of partnerships to commercialize our products. We also distribute and market other companies’ products. Through these measures, we have established a global position in both public and private markets.
• We act as a marketing, sales and distribution partner for numerous companies, including:
• Sanofi pasteur – MSD. We act as marketing, sales and distribution partner for part of the SPMSD portfolio in Sweden.
• Novartis Vaccines and Diagnostics. We act as marketing, sales and distribution partner for part of the Novartis vaccine
portfolio in Sweden.
• Statens Serum Institute Denmark. We act as marketing, sales and distribution partner for a number of SSI products in
Spain and Sweden.
• Green Cross Corporation Korea. We act as marketing, sales and distribution partner of GreenCross Corporation’s
Japanese encephalitis vaccine in Europe.
• Netherlands Vaccine Institute. We act as marketing, sales and distribution partner of part of NVI’s product portfolio in
the Benelux (Belgium, Netherlands, Luxembourg).
• Talecris Biotherapeutics. We act as marketing, sales and distribution partner of Talecris’s product Prolastin in nine
Western European countries.
We have developed a network of companies that market and sell our products. The most significant collaborations in
terms of current sales value are:
• Baxter International Inc. – A marketing, sales and distribution partner for a certain vaccines in Austria, Germany,
Greece and Russia.
• Infectopharm Germany – A marketing, sales and distribution partner for our flu vaccine in Germany.
• Masta UK – A marketing, sales and distribution partner for our travel vaccines in the UK.
• Novartis-Behring – A marketing, sales and distribution partner for our travel vaccines in Germany.
• Sanofi pasteur – A marketing, sales and distribution partner for Dukoral in Canada, Australia and a number of other
countries outside Europe and the U.S..
• Sanofi pasteur – MSD – A marketing, sales and distribution partner for our flu vaccine in the UK.
• Kedrion – A marketing, sales and distribution partner for our flu vaccine in Italy.
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GEGEVENS KANDIDATEN RAAD VAN COMMISSARISSEN

De heer Stephen Brown (Steve) Davis (1957) is momenteel verbonden als consultant aan een reeks van projecten, waaronder als interim CEO bij IDRI (Infectious Diseases Research Institute) in Seattle en als universitair docent in intellectueel eigendomsrecht aan de University of Washington law school. Hij heeft verder zitting in tal van besturen. De heer Davis was tot 2007 CEO van Corbis Corporation en treedt momenteel op als senior advisor van de onderneming. Corbis is een wereldwijde digitale mediaonderneming, en privé-eigendom van Bill Gates. Gedurende zijn tienjarig dienstverband als CEO van Corbis heeft de heer Davis de onderneming zien veranderen van een internet start-up tot een gevestigde marktleider met jaaromzetten van meer dan USD 250 miljoen, en meer dan 1.100 werknemers. Voordat hij CEO was bekleedde de heer Steve Davis diverse functies bij Corbis als Corporate Attorney, VP Strategy Development, en als General Counsel.
De heer Steve Davis werkte verder als advocaat bij Preston Gates & Ellis, in Seattle, waar hij gespecialiseerd was in intellectueel eigendomsrecht. Verder bekleedde hij functies bij de Hoge Commissaris van de Verenigde Naties voor Vluchtelingen, en bij diverse herhuisvestingprogramma's voor vluchtelingen.
De heer Steve Davis is momenteel lid van de Board of Trustees van PATH, een non-profit organisatie die zich bezighoudt met de verbetering van de gezondheidszorg in ontwikkelingslanden, en een van de grootste begunstigden van de Bill & Melinda Gates Foundation. Hij is lid van de Board of Trustees, Voorzitter van de Tech Transfer Committee en Executive Committee/Board Secretary van de Fred Hutchinson Cancer Research Centre, een van de grootste instituten op het gebied van kankeronderzoek in de wereld. Andere organisaties waar de heer Steve Davis een bestuursfunctie bekleedt zijn Intrepid Learning Solutions, Seattle Foundation, en PlanetOut Inc. Hij is verder lid van de Council of Foreign Relations. De heer Steve Davis heeft bestuursfuncties bekleedt bij diverse organisaties, waaronder Npower en de Washington State Technology Alliance.
De heer Steve Davis heeft een Bachelor of Arts van de Princeton University, een Master of Arts van de University of Washington en een Doctorate in Law aan de Columbia University School of Law. Hij heeft diverse certificaatprogramma's afgerond aan de Universiteit van Bejing en de Stanford University Executive Business School.


GEGEVENS KANDIDATEN RAAD VAN BESTUUR

De heer dr. Cees de Jong trad in september 2007 aan als Chief Operating Officer van Crucell.
In februari 2008 werd hij benoemd tot de Raad van Bestuur.
In zijn hoedanigheid van COO van Crucell is hij verantwoordelijk voor Clinical & Process Development, Manufacturing & Supply Chain, en voor Marketing & Sales. Verder rapporteren de volgende Support Functions aan hem: Human Resource Management, Information Technology and Services, Quality Assurance & Quality Control, en Controlling & Planning.
Gedurende de laatste vier (4) jaar werkte de heer Cees de Jong bij Quest International, een ICI onderneming. Hier was hij lid van het bestuur en verantwoordelijk voor de Flavours Division, die bij zijn aantreden nog verliesgevend was, maar onder zijn leiding veranderde in een divisie die de groeicijfers van de branche overtrof. Voordat hij bij Quest aantrad was hij Directeur bij DSM Anti-infectives, een wereldwijde onderneming met een jaaromzet van USD 625 miljoen en meer dan 4.000 werknemers.
In 1989 startte de heer de Jong zijn carrière bij Gist Brocades, waar hij diverse posities bekleedde in Business Development, Strategy en General Management, voordat de onderneming in 1998 door DSM werd overgenomen. De heer de Jong heeft een medische graad en behaalde een MBA aan de Erasmus Universiteit Rotterdam, Nederland.
De heer de Jong is verder Voorzitter van de Raad van Bestuur van GreenChem, een onderneming in Breda die gespecialiseerd is in bijzondere chemicaliën.
De heer Cees de Jong heeft twee dochters en speelt waterpolo. Hij is gediplomeerd piloot en vliegt als hij tijd heeft erop uit met eenmotorige vliegtuigen.
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Luc Soete – Frankrijk biedt meer: concurreren om het onderzoek van Organon
Crucell, vlaggeschip van de Nederlandse biotechsector, wordt opgekocht. Waarom zou dit beter aflopen dan de verkoop van Organon eerder?
Afgelopen week bracht het Amerikaanse Johnson & Johnson (J&J) een bod uit van zo’n 1,7 miljard euro op Crucell, het bekende biotechbedrijf van het Leidse Bio Science Park. Vorige maand werd de beslissing over de sluiting van Organon BioSciences door Merck Sharp & Dohme (MSD) uitgesteld tot eind dit jaar.
De farmasector is volop in beweging. Of een J&J Crucell dezelfde weg zal inslaan als MSD Organon nu, wordt op het ogenblik van het aanlokkelijke bod uiteraard sterk betwijfeld. Crucell is sterk ingebed in het Leidse universitaire onderzoek en J&J zou juist behoefte hebben aan de gespecialiseerde vaccinkennis van Crucell. Toch dringen zich op termijn precies dezelfde vragen op. Want wat als straks een Glaxo Smith Kline (GSK), wereldleider op het gebied van vaccins, J&J overneemt? Goed dus om toch in wat meer detail te kijken hoe het zo ver kon komen met Organon Biosciences en wat de verschillen zijn met Crucell nu. Voor de goede orde: het in één klap schrappen van alle Organon-onderzoeksactiviteiten zou voor Nederland met zijn relatief kleine private onderzoeksinfrastructuur ongekend zijn: een daling in het totale private Nederlandse onderzoekersbestand van bijna 5 procent.
Eerste verschil tussen Crucell en Organon is uiteraard de – naar nu blijkt – fatale lastminutebeslissing van de AkzoNobel-directie om Organon toch niet naar de beurs te brengen en aan het toenmalige Amerikaanse Schering- Plough te verkopen. De 11 miljard euro was een mooi bedrag voor de aandeelhouders van AkzoNobel en maakte het de multinational mogelijk het Britse ICI op te kopen en zo wereldleider te worden in de verfsector.
Maar het was een beslissing tegen de directie van Organon in. Het heeft de Nederlandse kenniseconomie ook niets opgebracht. Integendeel, Akzo verrichtte in 2008 in Nederland nog amper 67 miljoen euro aan onderzoek, Organon Biosciences 400 miljoen – 400 miljoen die nu dreigt te verdwijnen naar de VS, Frankrijk en Zwitserland. Met verf werd AkzoNobel misschien rijk, Nederland niet.
De directie van Crucell staat nu wel achter het bod en ziet in J&J de ideale partner. Dat heeft alles van doen met een tweede factor: de snelle veranderingen in het farmaonderzoek. De ontwikkeling van nieuwe geneesmiddelen is slechts rendabel dankzij octrooien. In principe gedijt privaat onderzoek goed in zo’n omgeving. Bedrijven zijn bereid te investeren in risicovolle onderzoeksactiviteiten omdat er bij succes binnen de beperkte periode van het octrooi, en zeker wanneer het om breed toepasbare geneesmiddelen gaat, forse monopoliewinsten gerealiseerd kunnen worden. Maar blockbuster -geneesmiddelen vinden wordt steeds moeilijker en de onderzoeksrisico’s steeds groter. Grote farmabedrijven hebben het moeilijk voldoende nieuwe medicijnen te ontwikkelen om de steeds grotere onderzoeksomvang uit eigen winsten te financieren.
De schaalvergroting op wereldniveau die het farmaonderzoek de laatste jaren gekend heeft, lijkt dan ook steeds meer op een vlucht naar voren: omdat het eigen onderzoek niet genoeg oplevert, wordt gezocht naar nieuwe overnames. Zo werd de overname van Schering-Plough door Merck vooral ingegeven door de behoefte bij MSD snel een aantal producten in ontwikkeling (R&D-pijplijnen) op te kopen. Maar zelfs het opkopen van daarvan bij concurrenten is onvoldoende om de toekomst van MSD veilig te stellen.
Binnen het bedrijf werd een divisie opgericht met de naam External Discovery and Preclinical Science (XDPS), die gevuld moet worden met vanuit de eigen R&D-pijplijn vormgegeven externe samenwerkingen. In die zin worden de grote farmabedrijven als het ware distributieplatforms die vooral actief zijn in de ontwikkelingsfase, inclusief regelgeving, en wereldwijde marketing voor hun rekening nemen. Een model dat ook opkomt in andere sectoren als consumentenelektronica waar een bedrijf als Apple een gelijkaardige rol uitbouwt in relatie tot de zogenoemde apps voor iPhone en iPad. In die zin verschillen Organon en Crucell wezenlijk van elkaar.
De derde factor is het onduidelijke Nederlandse en Europese kennisbeleid. Nederland heeft met het eerste innovatieplatform duidelijk gekozen voor een beperkte, zogeheten sleutelgebiedenaanpak. Kennisondersteuning zou beperkt blijven tot kritische kennisgebieden binnen de Nederlandse economie. Daar hoorde farma niet echt bij. Chemie met witte en groene life sciences wel.
Intussen bleven de onderzoekskosten in Nederland vrij hoog in verhouding tot andere landen. Zoals de grafiek aantoont, werd de generieke belastingsaftrek op onderzoeks- en ontwikkelingswerk, de zogeheten WBSO, binnen het kader van de crisisaanpak verbreed, maar blijft zij in bijdrage beperkt. In Frankrijk werd een veel radicaler R&D-belastingskrediet ingevoerd.
Dat de Franse president succes had met zijn telefoontje naar MSD-topman Clark had dus weinig van doen met wat er aan de telefoon werd gezegd, maar eerder met de vaststelling – die Clark wellicht al veel vroeger had gedaan – dat de onderzoekskosten in Frankrijk nu de laagste zijn in Europa en zo’n 35 procent lager liggen per onderzoeker dan in Nederland. Het roept de vraag op naar het gebrek aan Europees beleid.
Dat beleid lijkt wat het aantrekken van private investeringen in R&D betreft steeds meer op een beggar-thy-neigbour beleid: de Europese lidstaten beconcurreren elkaar met belastingsvoordelen zonder dat Europa er op enigerlei manier beter van wordt. In die zin zou het verdwijnen van Organon in Nederland niet veel goeds voorspellen voor de duurzaamheid van de overname van Crucell door J&J. Terwijl de concurrentie tussen de onderzoekslaboratoria van de grote farmabedrijven zelf moordend is – getuige het verdwijnen dit en volgend jaar van zo’n 550 onderzoeksposities bij dat andere J&J farmabedrijf in de Benelux, het Vlaamse Janssen pharmaceutica – blijken Europese overheden daar nog eens een schepje bovenop te doen.
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