Positive Phase I and Pre-Clinical Data Suggest Acambis' Influenza Vaccine Could Tackle Influenza Pandemics

Positive Phase I and Pre-Clinical Data Suggest Acambis' M2e-Based Universal Influenza Vaccine, ACAM-FLU-A(TM), Could Tackle Influenza Pandemics

Acambis plc (Acambis) (LSE:ACM), a leading vaccine development company, today announced positive data from two trials of its universal influenza vaccine ACAM-FLU-A(TM). The novel vaccine targets the M2e peptide, which is found unchanged on the surface of all 'A' strains of the influenza virus, including all pandemic influenza strains. As such, this vaccine could overcome the current need to adapt influenza vaccines every year to correspond to circulating strains. The Phase 1 clinical trial showed the vaccine to be well tolerated and immunogenic and the pre-clinical challenge study suggests that this M2e-based vaccine can protect against highly pathogenic viruses such as pandemic influenza strains, including H5N1.

Currently, influenza vaccines are regularly reformulated owing to the rapid mutation of the virus. ACAM-FLU-A(TM) combines the conserved M2e peptide with a carrier molecule from Hepatitis B, which is used to help stimulate the immune system. This novel vaccine design means that ACAM-FLU-A(TM) could potentially provide protection against 'A' strains of influenza. Historically, influenza pandemics have only been caused by 'A' strains of the virus. Therefore ACAM-FLU-A(TM) has potential both as a vaccine against pandemic influenza and as part of seasonal influenza vaccination.

The Phase 1 trial was a double-blind, placebo-controlled study conducted at three centres in the USA. The study consisted of four arms: placebo, ACAM-FLU-A(TM) alone or combined with aluminium hydroxide or QS-21. Healthy volunteers aged between 18 and 40 were given two doses 30 days apart, their immune response against the M2 protein was tested after 60 days and any adverse events to the vaccine were recorded.

The vaccine was shown to be immunogenic and well-tolerated, with no serious adverse events. Whilst immune responses were seen in all the vaccinated groups, blood tests showed that the highest immune responses occurred in the group who received ACAM-FLU-A(TM) with QS-21. In this group, 90% of people who received ACAM-FLU-A(TM) plus QS-21 had antibodies to the M2 protein in their system. QS-21 Stimulon(R) adjuvant is an investigational adjuvant (immune stimulant) provided under an agreement with Antigenics Inc., which has recently been converted to a non-exclusive license and supply agreement.

The pre-clinical study tested the ability of an M2e-based vaccine to protect against the Vietnam 2004 strain(1) of H5N1 avian influenza (bird flu). The H5N1 virus was lethal in the placebo-treated group, whereas 70% of those in the group vaccinated with the M2e-based vaccine from the same influenza strain were protected.

Dr Michael Watson, Executive Vice President, Research & Development at Acambis commented: "Taken together, the data from these two trials demonstrate the potential of Acambis' approach to offer protection against 'A' strains of the influenza virus, including pandemic influenza strains. As a universal vaccine, ACAM-FLU-A(TM) can potentially overcome many of the drawbacks of existing influenza vaccines. It can be manufactured at any time of the year, and could be stockpiled in advance of a pandemic or potentially used routinely to ensure population protection against future pandemics."

Following these results, Acambis will explore partnering in parallel with continued development of ACAM-FLU-A(TM).

About Acambis

Acambis is a leading vaccine company developing novel vaccines that address significant unmet medical needs or substantially improve standards of care. ChimeriVax(TM)-JE, Acambis' most advanced product in its development-stage pipeline, has to date shown an excellent safety and efficacy profile following pivotal Phase 3 trials. It is currently undergoing paediatric trials in India and is partnered with Sanofi Pasteur and Bharat Biotech. Acambis' proprietary ChimeriVax(TM) technology, developed in association with St Louis University, has also been used to develop ChimeriVax(TM)-West Nile, which is undergoing Phase 2 clinical testing, making it the most advanced investigational vaccine against the West Nile virus. Acambis has established a global collaboration with Sanofi Pasteur for further development and commercialisation of the vaccine. ChimeriVax(TM) has also been applied to development of Sanofi Pasteur's tetravalent dengue vaccine, which has successfully demonstrated proof-of-concept in a Phase 2 trial by generating 100% seroconversion to all four dengue virus serotypes.

Acambis also has the only vaccine in development against Clostridium difficile bacteria, a leading cause of hospital-acquired infections. C. difficile is estimated to cause at least 360,000 cases of C. difficile-associated disease in the US alone with annual costs to the healthcare system of $3.2bn. Acambis' influenza programme aims to develop a universal vaccine against influenza, for which a universal 'A' strain vaccine, ACAM-FLU-A(TM), has completed a Phase 1 trial. It also includes various further vaccine candidates in the research and pre-clinical stages.

Acambis is recognised internationally as the leading producer of smallpox vaccines. Acambis' ACAM2000(TM) (Smallpox (Vaccinia) Vaccine, Live) vaccine for active immunisation against smallpox disease for persons determined to be at high risk for smallpox infection was licensed by the US Food and Drug Administration in August 2007. Acambis has manufactured doses of ACAM2000(TM) for emergency-use stockpiles held by the US Government and several other governments around the world. For safety and prescribing information, please refer to www.acambis.com/ACAM2000.

Acambis is based in Cambridge, UK and Cambridge, Massachusetts, US, and is listed on the London Stock Exchange (ACM). More information is available at www.acambis.com.

About influenza and influenza vaccines

Today, seasonal influenza represents the single largest vaccine market in the world, worth an estimated $2.2bn and projected to grow to $4bn by 2010(3). It is still a major global threat, which the WHO estimates causes between 250,000 and 500,000 deaths every year around the world(2)..Immunity against influenza viruses, whether acquired by natural infection or immunisation, is typically transient due to the virus's ability to mutate and evade pre-existing immunity. Accordingly, current licensed vaccines are updated on an annual basis to target most effectively the presently circulating strains.

Pandemic influenza viruses are sufficiently distinct from seasonal epidemic viruses that new vaccines must be developed to address them. Pandemic influenza vaccines, primarily targeting avian H5N1 viruses, are being stockpiled for emergency use. However, the efficacy of these vaccines may be negatively impacted by continual mutations in circulating H5N1 strains. Experts believe the next pandemic could cause disease in two billion people. Based on best-case scenarios modelled on the mild pandemic of 1968, this could result in two to seven million deaths. However, if the death toll associated with the 1918 influenza virus were applied to today's world population, there could be 180 to 360 million deaths globally.(4)

Currently, influenza vaccines are reformulated, generally each year, to address mutations in influenza strains (known as "antigenic drift"). Preparations are ongoing around the world for a potential pandemic, which would result from a major genetic change in the influenza virus (known as "antigenic shift"). The need to change vaccine formulations each year results in delays in initiating vaccination programmes. In addition, it is estimated that vaccine producers would need between three and six months to product a strain-specific vaccine against a pandemic strain.

About ACAM-FLU-A(TM)

ACAM-FLU-A(TM) is a recombinant vaccine that uses a hepatitis B core protein (HBc) to present M2e, the extracellular domain of the ion channel protein M2(5). M2 is one of the three proteins expressed on the surface of the 'A' strain influenza virus and of infected cells alongside haemagglutinin (HA) and neuraminidase (NA). Unlike HA and NA, M2 is highly conserved, albeit under natural conditions not easily recognised by the immune system. M2e could elicit an immune response to all influenza 'A' strains. As such, ACAM-FLU-A(TM) has the potential to be both a universal pandemic or pre-pandemic influenza vaccine and part of a universal seasonal vaccine. Historically, influenza pandemics have been caused by 'A' strains of the virus while seasonal vaccines target both 'A' and 'B' strains of the virus.


"Safe Harbour" statement

Statements contained within this news release may contain forward-looking comments, which involve risks and uncertainties that may cause actual results to vary from those contained in the forward-looking statements. In some cases, you can identify such forward-looking statements by terminology such as 'may', 'will', 'could', 'forecasts', 'expects', 'plans', 'anticipates', 'believes', 'estimates', 'predicts', 'potential', or 'continue'. Predictions and forward-looking references in this news release are subject to the satisfactory progress of research which is, by its very nature, unpredictable. Forward projections reflect management's best estimates based on information available at the time of issue.

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