• Crucell is developing a recombinant malaria vaccine based on our AdVac^® and PER.C6^® technology. 
• Studies conducted in large animals resulted in excellent immune responses for our 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.

We are developing a recombinant malaria vaccine based on our AdVac^® technology and produced on our PER.C6^® production technology. The vaccine is made by inserting the gene for the circumsporozoite protein (CSP) from the Plasmodium falciparum malaria parasite into an adenoviral vector, which acts as a 'vehicle' for vaccination delivery.

Despite earlier promising results in the 1960’s with prototype vaccines, there is no effective vaccine against malaria available today. Various treatments are available but due to the worsening problems of drug resistance in many parts of the world, adequate treatment of malaria is becoming increasingly difficult. In addition, many insecticides are no longer useful against mosquitoes transmitting the disease.

In a study carried out by New York University (NYU), the efficacy of our malaria vaccine candidate was tested in NYU’s mouse malaria model. The study showed that a single administration of a prototype AdVac^® vaccine protects mice upon challenge with the mouse specific parasite.

In March 2003, we entered into collaboration with the Walter Reed Army Institute of Research (WRAIR) and GlaxoSmithKline Biologicals (GSK) under a Cooperative Research and Development Agreement (CRADA). In line with this agreement, we have completed work with WRAIR and GSK to evaluate our AdVac^® malaria vaccine candidate. Our vaccine candidate was tested as a stand-alone vaccine and in combination with GSK’s RTS,S malaria vaccine candidate. These studies have shown that Crucell’s AdVac^® vaccine candidate efficiently primed and/or boosted malaria specific immune responses.

The GSK malaria vaccine candidate RTS,S has, as a stand-alone vaccine, been shown to confer partial protection to human volunteers in both a laboratory challenge model conducted at WRAIR and under natural challenge conditions in a field study conducted in the Gambia. Phase IIb pediatric trials conducted with RTS,S in Mozambique and reported in The Lancet medical journal in October 2004 and 2007 demonstrated further promising results, with the vaccine protecting some infants against infection and making the course of the disease less serious and life threatening in others.

In March 2004 it was announced that the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health (NIH), will support the development of our candidate malaria vaccine. The agreement has an estimated value of up to US$ 3.5 million and covers process development of the candidate AdVac-based malaria vaccine including the production of clinical trial material and Investigational New Drug (IND) filing. The work is being done under a subcontract agreement with Science Applications International Corporation (SAIC).

In partnership with the NIAID, Crucell’s malaria vaccine entered a Phase I trial in the US in Q4 2006. 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.

Malaria is one of today’s top three killers among communicable diseases. The disease currently represents one of the most prevalent infections in tropical and subtropical areas causing severe illness in 300 to 500 million individuals worldwide and causing one to three million deaths every year. Most of these deaths occur among children and pregnant women in the developing world, especially in sub-Saharan Africa. Unfortunately, mortality associated with severe or complicated malaria still exceeds 10-30%. Malaria is caused by the Plasmodium parasite and transmitted from person-to-person through the bite of a female Anopheles mosquito. Although the overwhelming majority of morbidity and mortality associated with malaria occur in the developing world, this disease also affects travelers.

For Press Releases and Scientific Papers that relate specifically to our Malaria program, please refer to the Malaria Media Kit.