Dutch biotechnology company Crucell N.V. (Euronext, NASDAQ: CRXL; Swiss Exchange: CRX) today announced that the Ebola vaccine it is developing in partnership with the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), has commenced its Phase I clinical study. The randomized, double-blind, placebo-controlled study in 48 healthy volunteers will test the single-shot vaccination in a dose-escalation trial.
The start of the trial follows the successful completion of the Investigational New Drug (IND) application process required by the Food and Drug Administration (FDA) in the US. In preclinical studies, a single shot of the PER.C6®-based vaccine protected monkeys completely against a lethal Ebola challenge. The Phase I study will be carried out by the VRC at the NIH Clinical Center in Bethesda, Maryland. The main factors under examination are the vaccine's safety, tolerability and immunogenicity.
"We are proud that another of our vaccines is progressing to the clinic, and the Ebola vaccine is the first employing our adenovirus vaccine technology to do so," said Jaap Goudsmit, Chief Scientific Officer at Crucell. "Crucell and the VRC have so far made significant progress together, and we now aim to take our partnership to the next level in developing a vaccine against this extremely dangerous disease."
About Ebola
The Ebola virus is one of the few viruses capable of causing hemorrhagic fever, a severe, often-fatal disease in humans characterised by high fever and massive internal bleeding. Among other hemorrhagic fevers including Marburg and Lassa, Ebola causes death in 50% to 80% of all cases. Ebola outbreaks occur regularly in tropical Africa, affecting both human and great ape populations. Since the Ebola virus was first recognized, approximately 2,000 cases with over 1,200 deaths have been reported. Ebola usually appears in sporadic outbreaks, and spreads within a health-care setting. Because of the high disease-related mortality rates and lack of any vaccine or therapy, the Ebola virus is on the US Centers for Disease Control and Prevention (CDC) category "A" list of bioterror agents, together with smallpox and anthrax.
About Crucell-VRC Partnership
Crucell has entered into a Cooperative Research and Development Agreement (CRADA) with the VRC (www.vrc.nih.gov) to jointly develop, test, and manufacture an adenovirus-based Ebola vaccine. Under the terms of the agreement, Crucell has an option for exclusive worldwide commercialization rights to the Ebola vaccine resulting from this collaboration. In August 2002, the CRADA was extended to cover vaccines against Marburg and Lassa infections. In March 2005, Crucell secured an exclusive license to certain patents of the NIH for the development and commercialization of recombinant vaccines against Ebola, and a US$ 21.4 million manufacturing contract was signed with the NIH in April 2005, under which Crucell will manufacture its recombinant adenovirus vector Ebola vaccine for clinical trials in humans.
Sanofi Pasteur PER.C6®-based Seasonal Influenza Vaccine Enters First Clinical Trial
* Flu vaccine based on new technology within U.S. Government
Preparedness Program
* Successful scale-up of PER.C6® to 20,000 liters
Lyon, France; Leiden, The Netherlands, September 26, 2006 - Sanofi pasteur, the vaccines business of the sanofi-aventis Group (NYSE: SNY), initiated its first clinical study today with a new generation of seasonal influenza vaccine produced using the PER.C6® cell culture technology of Dutch biotechnology company Crucell N.V. (Euronext, NASDAQ: CRXL; Swiss Exchange: CRX). This trial represents one of sanofi pasteur's initiatives to diversify flu vaccine manufacturing technologies.
The trial conducted in the United States is part of a contract awarded by the U.S. Department of Health and Human Services (HHS) to accelerate the development of a new cell culture-based influenza vaccine.
"This trial will assess the safety and ability to generate an immune response of a cell culture-based vaccine that could provide an important alternative to traditional flu vaccines," said Dennis Morrison, MD, Clinical Investigator at the first trial site, Bio-Kinetic Clinical Applications, Inc. in Springfield, Missouri. The clinical study is the first step toward sanofi pasteur filing a Biologics License Application for a cell culture-based trivalent split inactivated seasonal influenza vaccine with the Food and Drug Administration (FDA).
The phase I clinical trial will be conducted on 100 healthy adults, 18-64 years of age. Half of the study participants will receive the cell-based vaccine and the other half a traditional egg-based control vaccine. "We are pleased to participate in a study to evaluate the viability of the next generation of influenza vaccines," said Cynthia Strout, MD, Clinical Investigator at the second trial site, the Coastal Carolina Research Center in Mt. Pleasant, South Carolina.
This vaccine was developed using PER.C6® cell culture technology, licensed from Crucell. Cell culture technology could allow sanofi pasteur to reduce dependence on eggs while offering an additional reliable production technology.
The production scale potential of the PER.C6® cell line has been demonstrated in a successful bioreactor run of 20,000 liters. This project breaks new ground in vaccines technology by demonstrating effective large-scale production capacity using cell culture on a commercial scale. This scale-up process was achieved under a subcontracting agreement between sanofi pasteur and Lonza Biologics plc (Lonza Group).
As the world leader in the research, development and manufacture of influenza vaccine, sanofi pasteur is actively involved in other projects in the U.S. and Europe with the goal of developing new influenza vaccines.
Seasonal influenza overview
Influenza is a highly infectious virus that spreads easily from person to person, primarily when an infected individual coughs or sneezes. According to the World Health Organization (WHO), 5-15% of the population is affected with upper respiratory tract infections in annual influenza epidemics. Hospitalization and deaths mainly occur in high-risk groups (elderly, people with chronic conditions/illness). Although difficult to assess, these annual epidemics are thought to result in between three and five million cases of severe illness and between 250,000 and 500,000 deaths every year around the world. Most deaths currently associated with influenza in industrialized countries occur among the elderly over 65 years of age.
About PER.C6® Technology for Influenza Vaccine Production
Crucell's PER.C6® technology is a cell line developed for the large-scale manufacture of biological products including vaccines. PER.C6® cells are highly susceptible to influenza viruses, thereby making the production of large amounts of influenza vaccine feasible. Currently used influenza vaccines are produced using embryonated chicken eggs and there is value to improving the timely production of new vaccines in large quantities to combat a potential future influenza pandemic. A PER.C6®-based vaccine offers the possibility of advantages for both epidemic and pandemic preparedness. In comparison with other cell-culture technologies, PER.C6® offers advantages in terms of its safety and capacity for economic, large-scale production.
About sanofi Pasteur and Crucell exclusive agreement
Sanofi pasteur, the vaccines business of the sanofi-aventis Group, entered into a strategic and exclusive agreement with Crucell N.V. on December 31, 2003 to further develop, manufacture and market cell-based novel influenza vaccine products based on Crucell's proprietary PER.C6® cell line technology. The agreement covers both pandemic and seasonal influenza vaccines. Crucell retains commercial rights to the vaccine in Japan.
About sanofi-aventis
The sanofi-aventis Group is the world's third-largest pharmaceutical company, ranking number one in Europe. Backed by a world-class R&D organization, sanofi-aventis is developing leading positions in seven major therapeutic areas: cardiovascular disease, thrombosis, oncology, metabolic diseases, central nervous system, internal medicine, and vaccines. The sanofi-aventis Group is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).
Sanofi pasteur, the vaccines business of the sanofi-aventis Group, sold more than a billion doses of vaccine in 2005, making it possible to protect more than 500 million people across the globe. The company offers the broadest range of vaccines, providing protection against 20 bacterial and viral diseases. For more information, please visit: www.sanofipasteur.com / www.sanofipasteur.us
About Lonza Group
Lonza Biologics plc, is a biotechnology contract manufacturer and biologics service provider, which is a business sector of the Lonza Group, a chemical and biotechnology company driven by the life sciences, which generated sales of CHF 2.52 billion in 2005. Headquartered in Switzerland, Lonza, operates 23 production and R&D sites around the world. Lonza is listed on the SWX Swiss Exchange and for more information, please visit www.lonza.com.
About Crucell
Crucell N.V. (Euronext, NASDAQ: CRXL; Swiss Exchange: CRX) is a biotechnology company focused on research, development and worldwide marketing of vaccines and antibodies that prevent and treat infectious diseases. Its vaccines are sold in public and private markets worldwide. Crucell's core portfolio includes a vaccine against hepatitis B and a virosome-adjuvanted vaccine against influenza. Crucell also markets travel vaccines, such as the only oral anti-typhoid vaccine and the only aluminium-free hepatitis A vaccine on the market. The Company has a broad development pipeline, including both early-stage products and products almost ready to go to market. Several Crucell products are based on its unique PER.C6® production technology. The Company licenses this and other technologies to the biopharmaceutical industry. Important partners and licensees include DSM Biologics, sanofi aventis, GSK and Merck & Co. Crucell is headquartered in Leiden (the Netherlands), with subsidiaries in Switzerland, Spain, Italy and Korea. The Company employs about 900 people. For more information, please visit www.crucell.com.
Forward-looking statements
This press release contains forward-looking statements that involve inherent risks and uncertainties. We have identified certain important factors that may cause actual results to differ materially from those contained in such forward-looking statements. For information relating to these factors please refer to our Form 20-F, as filed with the U.S. Securities and Exchange Commission on July 6, 2006, and the section entitled "Risk Factors". The company prepares its financial statements under generally accepted accounting principles in the United States (US GAAP) and Europe (IFRS).
For further information please contact:
Crucell N.V.
Paul Vermeij
Director Investor Relations and Corporate Communications
Tel. +31-(0)71-524 8718
p.vermeij@crucell.com For Crucell in the US:
Redington, Inc.
Thomas Redington
Tel. +1 212-926-1733
tredington@redingtoninc.com
Crucell Announces WHO Prequalification for Quinvaxem(TM) Vaccine
Leiden, The Netherlands, September 26, 2006 - Dutch biotechnology company Crucell N.V. (Euronext, NASDAQ: CRXL; Swiss Exchange: CRX) announced today that Quinvaxem(TM), its fully-liquid pentavalent vaccine co-developed with Novartis Vaccines and Diagnostics, has been granted 'prequalification' by the World Health Organization (WHO).
Following the awarding of licensure by the Korea Food and Drug Administration (KFDA) in March 2006, WHO prequalification is a final prerequisite for the combination vaccine to be made available to supranational purchasing organizations. Supranational organizations are major customers for combination vaccines, which are used in mass vaccination programs in developing countries.
Crucell commenced production of Quinvaxem(TM) at the facility of its Korean subsidiary immediately following the vaccine's licensure by the KFDA. First batches of the product have recently been released by the KFDA and are available for sale. This puts Crucell in the position to now offer the product to the supranational organizations UNICEF and PAHO.
"WHO prequalification for Quinvaxem(TM) marks an important milestone for Crucell as we pursue our strategy of becoming a leading vaccine player," said Crucell's CEO, Dr Ronald H.P. Brus. "The public-private partnership between the United Nations Organizations, Crucell and Novartis over the many years of its development have made this innovative vaccine a reality. We believe this vaccine will make an important contribution to pediatric vaccination programs for the developing world, and will confirm Crucell's place as a leading supplier of such important vaccines."
Crucell said it expects Quinvaxem(TM) to become an important contributor to the Company's 2006 revenue forecast and its objective to achieve cash break-even in 2007.
Quinvaxem(TM) combines antigens for protection against five important childhood diseases: diphtheria, tetanus, pertussis (whooping cough), hepatitis B and Haemophilus influenzae type b, one of the leading causes of bacterial meningitis in children. It is the first internationally available fully-liquid vaccine containing all five of the above antigens to reach the market, offering a major advantage in terms of convenience of use. Current demand for the vaccine exceeds 50 million doses, with the annual demand expected to increase to more than 150 million doses per year over the next five years.
