• Crucell is developing a recombinant tuberculosis vaccine based on our AdVac^® and PER.C6^® technology.
• The development of this vaccine is being carried out in collaboration with the Aeras Global TB Vaccine Foundation.
• Studies in mice conducted in 2005 resulted in high immune responses towards the adenovector vaccine candidate.
• 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.
• 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. 

In collaboration with the Aeras Global Tuberculosis Vaccine Foundation, we are developing a recombinant tuberculosis vaccine based on our AdVac^® vaccine technology and our PER.C6^® manufacturing technology. Currently a series of three Phase I trials are taking place, with the first two studies indicating very promising results.

In 2004 we entered into a collaborative agreement with the Aeras Global TB Vaccine Foundation on the pre-clinical and clinical development of candidate tuberculosis vaccines. Aeras agreed to provide Crucell up to US$ 2.9 million contingent to meeting certain development milestones, for development of TB vaccine candidates. Under the terms of the agreement Crucell has the exclusive rights to register in developed countries.  

In 2005 an amendment of the contract was negotiated for € 700,000 to include additional development and production activities.

In 2006, Crucell tested a novel adenovector 35 (Ad35) based TB vaccine candidate in a challenge mouse model, an accepted animal model for TB vaccines. This study demonstrated that a single vaccination with the Ad35 TB vaccine could confer significant protection against infection and dissemination of Mycobacterium tuberculosis (M. tuberculosis). Partly based on these results, a decision was made to proceed to a Phase I trail.

In March 2007, Aeras committed a further US$ 5 million to the existing agreement with Crucell to support advanced development of the candidate AdVac^®-based tuberculosis vaccine.

A Phase I trial in the US in BCG naïve individuals has been completed. This randomized double blind, placebo controlled dose escalation study was conducted in healthy volunteers. All data has been collected, including the 6 months follow-up data. This is being analyzed and we expect initial findings to be made public in Q1 2008. No serious adverse side effects were reported to date. After demonstration of safety a dose escalation study will be conducted in infants/children using a less steep dose escalation study.

In May 2007, a second placebo controlled Phase I 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 and it continues to progress well. 

Tuberculosis is the world’s second deadliest infectious disease, with over 9 million new cases diagnosed in 2006. According to the World Health Organization (WHO), an estimated 1.7 million people died from tuberculosis in 2006. The current tuberculosis vaccine, developed over 85 years ago, reduces the risk of sever forms of tuberculosis in early childhood, but is not very effective in preventing pulmonary tuberculosis in adolescents and adults – the population with the highest rates of tuberculosis disease. In addition, extensively drug- resistant tuberculosis (XDR-TB) is hampering treatment and control efforts (see map above).