Crucell 2008
Combating Infectious Diseases
Annual Report and Form 20–F

• Our Products and Research & Development Pipeline
• Products
• Research & Development
  • Key pipeline developments
  • AdVac^® technology and AdVac^®-based vaccines
  • Antibodies
• Technologies

AdVac^® technology and AdVac^®-based vaccines

AdVac^® technology encompasses the use of adenoviral vectors such as Ad35 and Ad26 for vaccination against diseases caused by viruses, bacteria or parasites. These vectors are harmless adenoviruses that have been disabled so that they cannot replicate. A vector functions as an efficient ‘gene taxi’, delivering into the human body a fragment of DNA that carries the code for a protein from a specific pathogen. Once inside the body, the vectors express (produce) these proteins and present them to the person’s immune system, which mounts its protective response. Using this versatile vaccine vector platform in combination with PER.C6^® manufacturing technology, Crucell and partners are working to develop vaccines against diseases like tuberculosis, malaria, Ebola, Marburg and HIV.

Tuberculosis

Tuberculosis (TB) is a major cause of illness and mortality worldwide, with 9.2 million new cases and 1.7 million deaths due to TB in 2006. The current TB vaccine BCG, developed more than 85 years ago, is probably the world’s most widely used but least effective of vaccines. It does reduce the risk of disseminated TB, a form of the disease that spreads from the lungs to other organs, which is especially lethal in children. However, it does not reliably prevent pulmonary TB, the most prevalent form of TB, in both children and adults. The problem is compounded by the emergence of extensively drug-resistant tuberculosis (XDR-TB), which is hampering treatment and control efforts (see map on page 27 of the 2008 Annual Report).

To address this urgent need, Crucell is collaborating with the Aeras Global TB Vaccine Foundation to jointly develop the novel TB vaccine candidate AERAS-402/Crucell Ad35. Data from all trials conducted to date support the immunogenicity and safety of AERAS-402/Crucell Ad35 at all dose levels evaluated. A phase II study of this vaccine candidate is being conducted in Cape Town, South Africa, by the University of Cape Town Lung Institute in conjunction with the South African Tuberculosis Vaccine Institute.

Malaria

According to the WHO, malaria is one of the most prevalent infections in tropical and subtropical regions, causing severe illness in 300 t0 500 million people and death in 1 to 3 million people. Children and pregnant women are the groups most severely affected. No licensed vaccine is available to fight this disease.

Crucell is collaborating with the US National Institute of Allergy and Infectious Diseases (NIAID) on malaria vaccine research and development. A candidate vaccine arising from this partnership is being tested in a Phase I trial at two US sites: Vanderbilt University in Nashville, Tennessee and Stanford University in Palo Alto, California.

Ebola and Marburg

Crucell is developing a multivalent filovirus vaccine against Ebola and Marburg in collaboration with the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH). The candidate vaccine is based on Crucell’s proprietary adenoviral vector technology and is produced using Crucell’s PER.C6® technology. It is a recombinant DNA vaccine that expresses Ebola virus proteins in order to provide protection against infection with the Ebola virus.

HIV

Over the past 25 years, HIV infection resulting in AIDS has claimed the lives of nearly 25 million people, devastated entire communities, and enormously frustrated efforts to fight poverty, improve global health and promote economic development. In 2007, an estimated 2 million people died due to AIDS, 33 million people were living with HIV infection and 2.5 million people became infected with the virus. There is no licensed AIDS vaccine available.

With the support of a $19.2 million grant from the US National Institutes of Health, Crucell is collaborating with Harvard Medical School and its teaching hospital Beth Israel Deaconess Medical Center to develop an AdVac^®-based vaccine against HIV. Adenovirus serotype 26 (Ad26) is being used as the vaccine vector, in order to avoid the problem of pre-existing immunity to the more commonly used adenovirus serotype 5 (Ad5).