Total revenue and other operating income grew by more than 50% to
€213.1 million, compared to €140.9 million in 2006.
Successful Quinvaxem(TM) launch drives strong autonomous growth.
Strong operating cash flow of €51.5 million in the fourth quarter and €22.2 million for the year compared to a negative €54.0 million in 2006.
2008 full year guidance: total revenue and other operating income growth of 20% in constant currencies ; higher margins; positive cash flow.

• Sanofi pasteur enters into Phase II clinical trial with their seasonal flu vaccine. This vaccine is being developed using Crucell's PER.C6® cell line technology.
• Crucell and sanofi pasteur sign an exclusive collaboration and commercialization agreement for rabies antibodies for which Crucell received a payment of €10 million following the execution of the agreement and will be eligible for milestone payments of up to €66.5 million.
• Crucell presents results of two Phase I studies with the rabies monoclonal antibody cocktail (containing two antibodies), showing safety and ability to protect. The antibody cocktail, produced using Crucell's PER.C6® technology, is well tolerated, provides the expected neutralizing activity and can be administered in combination with a rabies vaccine.
• Crucell announces that its rabies monoclonal antibody cocktail has been granted Fast Track status by the US Food and Drug Administration's (FDA) Department of Health and Human Services.
• A US Phase I trial (in BCG naïve individuals) of the AdVac®/PER.C6® Technology-Based Tuberculosis Vaccine (in collaboration with the Aeras Foundation) has been completed. The results of the trial indicate that the vaccine is well tolerated and capable of stimulating cell mediated response to tuberculosis antigens. 
• Crucell announces that Merck & Co., Inc. has exercised an option to access Crucell's AdVac® vaccine technology and for the exclusive use of Crucell's PER.C6® technology in two infectious disease areas.
• Crucell announces that it has entered into a co-exclusive PER.C6® and AdVac® technology license agreement with Wyeth Pharmaceuticals, a division of Wyeth.
• Crucell discovers human monoclonal antibodies for the prevention and treatment of the avian flu virus. The antibodies provide immediate protection and neutralize the broadest range of H5N1 strains in pre- clinical models.
• Crucell and MedImmune sign an exclusive license and research collaboration agreement for the treatment and prevention of hospital-acquired bacterial infections.

• Strong growth of 35% in our pediatric, travel and other vaccines was offset by lower influenza vaccine sales in the fourth quarter of 2007 compared to 2006. In 2006 the majority of influenza sales occurred in the final quarter whereas in 2007 they were spread over the third and fourth quarter of the year.
• Combined total revenue and other operating income for the quarter of €75.9 million was in line with the same quarter of 2006 (€76.0 million) despite strong comparables and a weaker dollar. In addition, we received an initial payment of €10 million in cash for the rabies agreement with sanofi pasteur which we could not recognized as revenue in 2007 and had to defer to future years.
• Gross margin were 34% compared to 42% in the fourth quarter of 2006. Margins in the fourth quarter of 2006 were boosted by license revenues where fourth quarter 2007 margins were affected by inventory write-downs.

• Net loss for the fourth quarter came in significantly lower at €4.8 million versus a net loss of €24.9 million the same quarter of 2006.
• Net cash generated in operating activities in the fourth quarter was €51.5 million compared to net cash used of €2.5 million in the same quarter of 2006.
• Cash from operating activities before changes in net working capital resulted in a positive €13.1 million cash flow for the quarter. Changes in net working capital contributed significantly to cash from operating activities both for the fourth quarter as well as for the full year.

• The increase of over 50% in total revenue and total other operating income for the year to €213.1 million is primarily attributable to the successful roll-out of Quinvaxem(TM), an increase in travel vaccine sales and higher revenues related to acquisitions made in the second half of 2006.
• Net loss for the full year of €45.9 million compared to €87.6 million in the same period of 2006.
• Strong operating cash flow of €22.2 million for the year compared to a negative €54.0 million in 2006.

• Influenza - Seasonal Flu Vaccine (FluCell collaboration with sanofi pasteur): Based on Phase I clinical study results of the seasonal influenza vaccine developed by Crucell's partner sanofi pasteur, using PER.C6® technology, Phase II testing of the cell culture-based seasonal influenza vaccine was initiated in the U.S. This project is part of a contract awarded in 2005 by the U.S. Department of Health and Human Services (HHS) aimed at accelerating the development of a new cell culture-based influenza vaccine. Phase II trials involving healthy adult volunteers in the U.S. will focus further on the safety profile and immunogenicity of the cell-based vaccine.

• Influenza - Pandemic Flu Vaccine H9N2:  Phase I and II studies have been completed and the results are currently being analyzed. No serious adverse side effects were reported to date. Findings are expected to be released first half of 2008.

• Hepatitis A: Pediatric Epaxal® was licensed early 2007 in Switzerland. The product is currently under registration in selected endemic countries.
  
  

• Whole-killed West Nile Virus Vaccine: The Phase I trial for a vaccine was completed, demonstrating safety and tolerability. Crucell also developed human monoclonal antibodies for therapeutic use against West Nile. It has been decided that these programs will no longer be continued. Crucell has come to the conclusion that the commercial and market opportunities for its West Nile products are not as attractive as other products in Crucell's pipeline.

• Live Attenuated Yellow Fever Vaccine Flavimun®: Given the successful sales of the MoRuViraten® vaccine for Measles/Rubella, which is produced in the same facility as Flavimun®, Crucell's management has decided to further postpone the registration submission of the Yellow Fever vaccine in Switzerland. MoRuViraten® was successfully licensed in the first half of 2007 and its registration was renewed.

• AdVac®/PER.C6® Technology-Based Ebola Vaccine : For the Phase I study for the Ebola vaccine, which Crucell is currently developing in partnership with the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), two groups of 16 volunteers have been enrolled and vaccinated. The clinical data is still blinded, however initial indications suggest that the vaccine is safe at the tested doses and appears to be immunogenic in a subset of subjects.
• AdVac®/PER.C6® Technology-Based Tuberculosis Vaccine:  The development of this vaccine is being carried out in collaboration with the Aeras Global TB Vaccine Foundation. A US Phase I trial (in BCG naïve individuals) has been completed. The results of the trial, which will be presented by Aeras in April 2008 at a TB vaccines conference in Atlanta, indicate that the vaccine is well tolerated and capable of stimulating cell mediated response to tuberculosis antigens.  In Q2 2007 a second clinical trial was initiated in South Africa. This Phase I trial is a placebo controlled study in adults who were vaccinated at birth with the BCG vaccine. Enrolment has been completed and follow up is ongoing. The study shows the vaccine to be well tolerated. A new Phase I BCG-Ad35 prime boost clinical trial of the unique AdVac®-based tuberculosis vaccine was initiated in December 2007.

• AdVac®/PER.C6® Technology-Based Malaria Vaccine: Crucell and its partner, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), are conducting a Phase I trial in the U.S. The study is being carried out on two sites, VanderBilt and Stanford University. The first and second cohorts, comprising 18 and 17 volunteers respectively, have been successfully enrolled. No serious adverse side-effects have been reported to date. Current plans call for subsequent enrollment of two additional cohorts at higher vaccine doses, provided the vaccine has an appropriate safety profile. Following review of the safety data by a Safety Monitoring Committee, a decision has been made to begin recruitment of the third cohort. Initial findings of this Phase I trial are expected to be available in 2008.

• Merck Ad5 HIV vaccine: Discontinued

• AdVac®/PER.C6® Technology-Based HIV Vaccine: The Investigational New Drug Application (IND) for Phase I of the trial with Harvard Medical School (supported by the NIH) has been approved by the FDA in January 2008. Phase I of the trial is expected to start before the end of the first quarter of 2008.

• Rabies Human Monoclonal Antibody Cocktail: Crucell and sanofi pasteur signed an exclusive collaboration and commercialization agreement for the development of a rabies monoclonal antibody cocktail using Crucell's PER.C6® manufacturing technology. This antibody cocktail is to be used with the rabies vaccine for post-exposure prophylaxis against this fatal disease. Due to promising Phase I results of a US and an Indian study completed in 2007, in which no serious adverse effects were reported and the treatment was well tolerated, Crucell was notified by the FDA Department of Health and Human Services that its rabies monoclonal antibody cocktail has been granted a Fast Track designation. Under the terms of the agreement, Crucell will continue to perform the development activities. Crucell will be responsible for the manufacturing of the final product and will retain exclusive distribution rights in Europe, co-exclusive distribution rights in China and the rights to sell to supranational organizations such as UNICEF. In December 2007, Crucell received a payment of €10 million following the execution of the agreement and will be eligible for milestone payments of up to €66.5 million.
  

• Human Monoclonal Antibodies Against Flu H5N1: Crucell's scientists discovered a set of human monoclonal antibodies that provides immediate protection and neutralizes the broadest range of H5N1 strains in preclinical models. These results, demonstrating the potential of human monoclonal antibodies for pandemic preparedness, were presented on September 27th, 2007 at the 5th International Bird Flu Summit held in Las Vegas, Nevada. A total of twenty-one human monoclonal antibodies were discovered. These were found to be able to neutralize the H5N1 virus of avian influenza, which currently presents a global threat. The most potent of the antibodies was shown to neutralize the broadest range of H5N1 strains that have emerged between 1997 and 2004. This antibody prevents flu, in pre-clinical models, when given twenty four hours before a challenge with a lethal dose of highly pathogenic H5N1 virus. When given three days after infection, it also was shown to prevent death and cure the disease. Therefore this antibody may provide a powerful tool in pandemic preparedness.

• Blood Coagulation Factor VL/C: Conclusive proof of concept for this blood coagulation factor has not been established to date. Preclinical work on this program continues and we will provide a complete status update during the Analyst Day on March 12th, 2008 in London.

• Crucell signed a marketing and distribution agreement with Sanquin, the Dutch Blood Supply Foundation. Under the terms of the agreement, Crucell will get exclusive distribution rights of Cofact® Sanquin's prothrombin complex of blood factors II, VII, IX and X. This is currently in MRP (mutual recognition procedure) registration in a number of Crucell's key markets including Norway, Sweden, Denmark, Spain and Italy.  Crucell will also have a right of first refusal for China, Korea and a number of Eastern European countries.

• Crucell announced the sale of its share in Pevion Biotech, Bern (Switzerland) to other shareholders of Pevion Biotech Ltd. This resulted in net proceeds of approximately CHF 10 million (€6 million).

• Crucell and MedImmune announced an exclusive license and research collaboration agreement for the treatment and prevention of hospital-acquired bacterial infection. Under the terms of the agreement, MedImmune is to provide Crucell certain upfront, annual and milestone payments potentially exceeding US$ 40 million, plus research and development (R&D) funding and an undisclosed royalty on product sales. In return, Crucell has granted MedImmune an exclusive license to research, develop and commercialize antibodies within one of its MAbstract® technology programs. In addition MedImmune will have access to Crucell's antibody capabilities for further R&D in this area.
• Crucell and DSM Biologics announced a non-exclusive PER.C6® research licensing agreement with Recepta Biopharma S.A. This agreement allows Recepta Biopharma S.A. to use Crucell's PER.C6® technology to develop four antibodies it has licensed in from the Ludwig Institute for Cancer Research. Financial details were not disclosed.

• Crucell's Supervisory Board will propose Mr. Steve Davis as member of the Supervisory Board to Crucell's shareholders to appoint at the company's AGM on May 30, 2008. Mr. Davis (1957) was CEO of Corbis Corporation until 2007 and now acts as a senior advisor to the company. Corbis is a global digital media business privately owned by Bill Gates. During Mr. Davis' 10-year tenure as CEO of Corbis Corporation, he oversaw the development of the company from an internet start-up to an established global leader with annual revenues of over US$ 250 million and with more than 1100 employees. Prior to his role as CEO, Mr. Davis held several roles at Corbis as Corporate Attorney, VP Strategy Development and General Council.
  
• Dr. Cees de Jong was nominated to join Crucell's Management Board. This nomination will be proposed to Crucell's shareholders at the company's AGM on May 30, 2008. Dr. de Jong joined Crucell as Chief Operating Officer in September 2007 and in that responsibility he already is part of Crucell's Management Committee, which is responsible for the company's day-to-day operations. Crucell's Management Board is responsible for setting the company's goals, defining its strategy and achieving strong results. The current members are Chief Executive Officer Dr. Ronald Brus (Chairman), Chief Scientific Officer Dr. Jaap Goudsmit and Chief Financial Officer Mr. Leonard Kruimer. Before Dr. De Jong joined Crucell, he worked at Quest International as a member of the Board. He was responsible for the Flavours Division, which he turned around from loss making to outperforming industry growth rates. Prior to Quest, he worked as Managing Director of DSM Anti-infectives. In 1989 Dr. De Jong started his career at Gist Brocades, holding a variety of roles in Business Development, Strategy and General Management. Dr. De Jong holds a Medical Degree and earned an MBA at the Erasmus University Rotterdam.

• Crucell N.V. reacted to a press release issued by German company CEVEC Pharmaceuticals GmbH. In their press release of 14 January 2008, CEVEC announced that one of Crucell's PER.C6® patents for protein production was restricted by a recent decision of the European Patent Office. Crucell stated that the suggestions made in CEVEC's press release are misleading. On 7 December 2007, the opposition division of the European Patent Office maintained Crucell's patent for protein production (EP1161548), with only a minor limitation to a claim that is not relevant to the scope of protection of the patent.

• One STAR® patent (STAR67, used in STAR® constructs) was granted in Europe.
• A PER.C6® protein production method patent was granted in the U.S.
• An important AdVac®-related patent was granted in the U.S.
• Crucell's position in the AdVac® field was strengthened further with patents in the U.S. and in South Korea for the widely used Ad35 vector.
• A basic PER.C6® patent was granted in Japan.
• A PER.C6® patent for virus production was granted in Hong Kong.
• A Malaria vaccine based on AdVac® technology was granted in the U.S.
• A basic patent for STAR® technology was granted in Australia and Mexico.

• Crucell signed a non-exclusive STAR® research license agreement with Korean-based ISU ABXIS. The license covers both a research evaluation of STAR® technology for the production of recombinant proteins and an option for a commercial license. Financial details of the agreement were not disclosed.

PDF file with figures