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Final results from a large-scale Phase III trial of the RTS,Smalaria vaccine candidate, including the impact of a booster dose,published today in The Lancet,show that the vaccine candidate helped protect children and infants from clinical malaria for at least three years aſter first vaccinaon. The latest results demonstrated that vaccinaon with RTS,S, followed by a booster dose of RTS,S administered 18 months aſter the primary schedule, reduced the number of cases of clinical malaria in children (aged 5-17 months at first vaccinaon) by 36%to the end of the study 1 (over an average follow-up of 48 months across trial sites) and in infants (aged 6-12 weeks at first vaccinaon) by 26% to the end of the study (over an average follow-up of 38 months across trial sites). Efficacy decreased over me in both age groups. Without the booster dose, the 3-dose primary schedule reduced clinical malaria cases by 28% in children and 18% in infants to the study end.The efficacy of RTS,S was evaluated in the context of exisng malaria control measures, such as inseccide treated bed nets, which were used by approximately 80% of the children and infants in the trial. For children in the 5-17 month age category who received a booster dose 18 months aſter the primary schedule, an average of 1,774 cases of clinical malaria were prevented for every 1,000 children vaccinated across the trial sites, over an average of 48 months of follow-up. For infants aged 6-12 weeks at first vaccinaon with RTS,S, who received a booster dose, 983 cases of clinical malaria, on average, were prevented for every 1,000 infants vaccinated across trial sites over an average of 38 months of follow-up. More cases were averted in areas of higher malaria transmission. In the absence of a booster dose, 1,363 cases of clinical malaria were prevented, on average, for every 1,000 children aged 5-17 months at first vaccinaon and 558 cases for every 1,000 infants aged 6-12 weeks at first vaccinaon to the end of the study. Stascally significant efficacy against severe malaria to the end of the study period was observed only in children who received the booster dose.There was indicaon of increased risk for severe malaria in children who did not receive the booster dose, compared to those in the control group. Eleven research centres in seven African countries 2 conducted the efficacy and safety trial, in partnership with GSK and the PATH Malaria Vaccine Iniave (MVI), with grant funding from the Bill & Melinda Gates Foundaon to MVI. The trial, started in March 2009 and concluded in January 2014, enrolled 15,459 parcipants, in two age categories: children (aged 5-17 months at first vaccinaon) and infants (aged 6-12 weeks at first vaccinaon). Safety RTS,S connued to display an acceptable safety and tolerability profile during the enre study period. The incidence of fever in the week aſter vaccinaon was higher in children who received RTS,S than in those receiving control vaccine. In some children who experienced fever, thefebrile reacon was accompanied by generalized convulsions, but all those affected fully recovered within seven days. The meningis signal previously reported remains in the older age category, including two cases reported aſter the booster dose of RTS,S.Thiscould be a chance finding, as comparisons were made across groups for many different diseases, and because some of these cases happened years aſter vaccinaon without any obvious relaonship to vaccinaon. The occurrence of meningis will be followed closely during Phase IV studies, if RTS,S is licensed. Prof Francis Marnson, a principal invesgator in the trial in Malawi said “Malawi has tried for a long me to reduce the burden of Malaria in children. The efforts have paid off in the last couple of years as the prevalence has reduced. However Malaria sll connues to be a huge burden on the health sector with children being the most affected. So we need to connue to look for other tools to add to the exisng prevenon measures to further protect our children from geng Malaria. Today we report the success of a vaccine that have shown to be effecve in prevenng acquision of Malaria in children.We salute the children of Malawi and their parents who through their parcipaon have contributed to this successful story. We look forward to the day when children will go to the clinic and be vaccinated to be protected against Malaria.” Dr KwakuPoku Asante, a principal invesgator in the trial and chairperson of the RTS,S Clinical Trials Partnership Commiee said “We finally have in our sights a candidate vaccine that could have a real impact on this terrible disease that affects many children during their first years of life. The large number of children affected by malaria, somemes several mes per year, means that this vaccine candidate, if deployed correctly, has the potenal to prevent millions of cases of malaria. On behalf of the African sciensts and research centres that worked on the RTS,S trial, we give thanks to our naonal health authories, and to the trial parcipants, for enabling us to reach this important milestone.” Dr MoncefSlaoui, Chairman Global Vaccinesat GSK, said: “We are extremely encouraged that the results point to connued and significant public health benefit for those children whose lives are so disrupted by this awful disease.We might reasonably now expect that the impact of this vaccine candidate when used with exisng intervenons will allow more children to survive the early years which we know is the most dangerous me to be infected with malaria. We are working hard to submit the necessary evidence to regulatory authories and the World Health Organisaonso that they can take an informed decision on whether theRTS,S vaccine candidateshould be made available as an addional tool for malariaprevenon.” Dr David C. Kaslow, Vice President of Product Development at PATH, said: “Credit for reaching this scienfic milestone goes to the thousands of African families and hundreds of sciensts, clinicians, and health professionals who have made a commitment for many years to this vaccine trial. The public- private partnership behind RTS,Shas successfully collected pivotal human efficacy and safety data that regulators and policymakers can now use to decide on its use. While eradicaon is the ulmate goal, malaria has yet to be eliminated or even fully controlled in many parts of the world;these data suggest that malaria vaccines can help us take some crical steps along that path.” Next steps The European Medicines Agency (EMA) is currently reviewing the regulatory applicaon for RTS,S through the Art. 58 procedure iniated in July 2014. A posive opinion from the EMA’s Commiee for Medicinal Products for Human Use, together with a potenal policy recommendaon from the World Health Organisaon (ancipated by the end of 2015), would be the basis for licensure applicaons to Naonal Regulatory Authories in sub-Saharan African countries. If posive, these regulatory decisions would help pave the way for the introducon of RTS,S through African naonal immunisaon programmes. If RTS,S is approved, GSK has commied to making the vaccine available at a not-for-profit price. UNC Project Lilongwe- is a collaboraon between the University of North Carolina at Chapel Hill and Ministry of Health. It started doing research in Malawi in the early 1990s. Its mission is to idenfy innovave, culturally acceptable and relavely inexpensive methods for reducing the risk of HIV, Sexually Transmied Infecons (STI), Tuberculosis (TB), Malaria transmission and cancer through research;strengthenlocal research capacity through training and technology transfers andimprove paent care capacity and delivery. It mainly operates from Kamuzu Central Hospital, Bwaila Hospital, Area 18, 25 and Kawale Health Centres. Over the years, its operaons have expanded to cover health facilies in the Central West Zone including Lilongwe, Dedza, Kasungu, Ntcheu, Dowa, Mchinji and Salima. Find us for more informaon at www.id.unc.edu/malawi GSK – one of the world’s leading research-based pharmaceucal and healthcare companies – is commied to improving the quality of human life by enabling people to do more, feel beer and live longer. For further informaon please visit www.gsk.com. Cauonary statement regarding forward-looking statements GSK cauons investors that any forward-looking statements or projecons made by GSK, including those made in this announcement, are subject to risks and uncertaines that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D ‘Risk factors’ in the company’s Annual Report on Form 20-F for 2014. PATH is the leader in global health innovaon. An internaonal non-profit organizaon, we save lives and improve health, especially among women and children. We accelerate innovaon across five plaorms—vaccines, drugs, diagnoscs, devices, and system and service innovaons—that harness our entrepreneurial insight, scienfic and public health experse, and passion for health equity. By mobilizing partners around the world, we take innovaon to scale, working alongside countries primarily in Africa and Asia to tackle their greatest health needs. Together, we deliver measurable results that disrupt the cycle of poor health. Learn more at www.path.org. The PATH Malaria Vaccine Iniave (MVI) is a global program established at PATH through an inial grant from the Bill & Melinda Gates Foundaon. MVI’s mission is to accelerate the development of malaria vaccines and catalyze mely access in endemic countries. MVI’s vision is a world free from malaria. For more informaon, please visitwww.malariavaccine.org. 1 Intenon to Treat (ITT) analysis, for this stascal reference and those that follow 2 Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania CONTACT INFO FOR MEDIA CONTACTS Malawi Media enquiries: Tapiwa Tembo +265 (0) 881589725 (Malawi) Pora Kamthunzi +265 (0) 999553034 (Malawi) Francis Marnson +265 (0) 888838388 (Malawi) Nelecy Chome +265 (0) 888338631 (Malawi) GSK enquiries: UK Media enquiries: David Mawdsley +44 (0) 20 8047 5502 (London) Simon Steel +44 (0) 20 8047 5502 (London) David Daley +44 (0) 20 8047 5502 (London) Catherine Hartley +44 (0) 20 8047 5502 (London) Sarah Spencer +44 (0) 20 8047 5502 (London) Claire Brough +44 (0) 20 8047 5502 (London) US Media enquiries: Sarah Alspach +1 202 715 1048 (Washington, DC) Mary Anne Rhyne +1 919 483 0492 (North Carolina) Melinda Stubbee +1 919 483 2510 (North Carolina) JenniLigday +1 202 715 1049 (Washington, DC) Karen Hagens +1 919 483 2863 (North Carolina) Analyst/Investor enquiries: ZibaShamsi +44 (0) 20 8047 5543 (London) Tom Curry + 1 215 751 5419 (Philadelphia) Gary Davies +44 (0) 20 8047 5503 (London) James Dodwell +44 (0) 20 8047 2406 (London) Jeff McLaughlin +1 215 751 7002 (Philadelphia) All PATH Malaria Vaccine Iniave (MVI) media enquiries: Ellen Wilson at +1 301 280 5723 or ewilson@ burness.com PRESS RELEASE Malaria vaccine candidate hasdemonstratedefficacy over 3-4 years of follow-up Final results from Phase III trialsuggest substanal public health benefitscould be provided by the RTS,S malaria vaccine candidate in endemic regions in sub-Saharan Africa Vaccine efficacy enhanced by administraon of a booster dose

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  • Final results from a large-scale Phase III trial of the RTS,Smalaria vaccine candidate, including the impact of a booster dose,published today in The Lancet,show that the vaccine candidate helped protect children and infants from clinical malaria for at least three years after first vaccination.

    The latest results demonstrated that vaccination with RTS,S, followed by a booster dose of RTS,S administered 18 months after the primary schedule, reduced the number of cases of clinical malaria in children (aged 5-17 months at first vaccination) by 36%to the end of the study1 (over an average follow-up of 48 months across trial sites) and in infants (aged 6-12 weeks at first vaccination) by 26% to the end of the study (over an average follow-up of 38 months across trial sites). Efficacy decreased over time in both age groups. Without the booster dose, the 3-dose primary schedule reduced clinical malaria cases by 28% in children and 18% in infants to the study end.The efficacy of RTS,S was evaluated in the context of existing malaria control measures, such as insecticide treated bed nets, which were used by approximately 80% of the children and infants in the trial.

    For children in the 5-17 month age category who received a booster dose 18 months after the primary schedule, an average of 1,774 cases of clinical malaria were prevented for every 1,000 children vaccinated across the trial sites, over an average of 48 months of follow-up. For infants aged 6-12 weeks at first vaccination with RTS,S, who received a booster dose, 983 cases of clinical malaria, on average, were prevented for every 1,000 infants vaccinated across trial sites over an average of 38 months of follow-up. More cases were averted in areas of higher malaria transmission. In the absence of a booster dose, 1,363 cases of clinical malaria were prevented, on average, for every 1,000 children aged 5-17 months at first vaccination and 558 cases for every 1,000 infants aged 6-12 weeks at first vaccination to the end of the study.

    Statistically significant efficacy against severe malaria to the end of the study period was observed only in children who received the booster dose.There was indication of increased risk for severe malaria in children who did not receive the booster dose, compared to those in the control group.

    Eleven research centres in seven African countries2 conducted the efficacy and safety trial, in partnership with GSK and the PATH Malaria Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates Foundation to MVI. The trial, started in March 2009 and concluded in January 2014, enrolled 15,459 participants, in two age categories: children (aged 5-17 months at first vaccination) and infants (aged 6-12 weeks at first vaccination).

    SafetyRTS,S continued to display an acceptable safety and tolerability profile during the entire study period.The incidence of fever in the week after vaccination was higher in children who received RTS,S than in those receiving control vaccine. In some children who experienced fever, thefebrile reaction was accompanied by generalized convulsions, but all those affected fully recovered within seven days.

    The meningitis signal previously reported remains in the older age category, including two cases reported after the booster dose of RTS,S.Thiscould be a chance finding, as comparisons were made across groups for many different diseases, and because some of these cases happened years after vaccination without any obvious relationship to vaccination. The occurrence of meningitis will be followed closely during Phase IV studies, if RTS,S is licensed.

    Prof Francis Martinson, a principal investigator in the trial in Malawi said Malawi has tried for a long time to reduce the burden of Malaria in children. The efforts have paid off in the last couple of years as the prevalence has reduced. However Malaria still continues to be a huge burden on the health sector with children being the most affected. So we need to continue to look for other tools to add to the existing prevention measures to further protect our children from getting Malaria. Today we report the success of a vaccine that have shown to be effective in preventing acquisition of Malaria in children.We salute the children of Malawi and their parents who through their participation have contributed to this successful story. We look forward to the day when children will go to the clinic and be vaccinated to be protected against Malaria.

    Dr KwakuPoku Asante, a principal investigator in the trial and chairperson of the RTS,S Clinical Trials Partnership Committee said We finally have in our sights a candidate vaccine that could have a real impact on this terrible disease that affects many children during their first years of life. The large number of children affected by malaria, sometimes several times per year, means that this vaccine candidate, if deployed correctly, has the potential to prevent millions of cases of malaria.On behalf of the African scientists and research centres that worked on the RTS,S trial, we give thanks to our national health authorities, and to the trial participants, for enabling us to reach this important milestone.

    Dr MoncefSlaoui, Chairman Global Vaccinesat GSK, said: We are extremely encouraged that the results point to continued and significant public health benefit for those children whose lives are so disrupted by this awful disease.We might reasonably now expect that the impact of this vaccine candidate when used with existing interventions will allow more children to survive the early years which we know is the most dangerous time to be infected with malaria. We are working hard to submit the necessary evidence to regulatory authorities and the World Health Organisationso that they can take an informed decision on whether theRTS,S vaccine candidateshould be made available as an additional tool for malariaprevention.

    Dr David C. Kaslow, Vice President of Product Development at PATH, said: Credit for reaching this scientific milestone goes to the thousands of African families and hundreds of scientists, clinicians, and health professionals who have made a commitment for many years to this vaccine trial. The public-private partnership behind RTS,Shas successfully collected pivotal human efficacy and safety data that regulators and policymakers can now use to decide on its use. While eradication is the ultimate goal,

    malaria has yet to be eliminated or even fully controlled in many parts of the world;these data suggest that malaria vaccines can help us take some critical steps along that path.

    Next steps

    The European Medicines Agency (EMA) is currently reviewing the regulatory application for RTS,S through the Art. 58 procedure initiated in July 2014.A positive opinion from the EMAs Committee for Medicinal Products for Human Use, together with a potential policy recommendation from the World Health Organisation (anticipated by the end of 2015), would be the basis for licensure applications to National Regulatory Authorities in sub-Saharan African countries. If positive, these regulatory decisions would help pave the way for the introduction of RTS,S through African national immunisation programmes. If RTS,S is approved, GSK has committed to making the vaccine available at a not-for-profit price.

    UNC Project Lilongwe- is a collaboration between the University of North Carolina at Chapel Hill and Ministry of Health. It started doing research in Malawi in the early 1990s. Its mission is to identify innovative, culturally acceptable and relatively inexpensive methods for reducing the risk of HIV, Sexually Transmitted Infections (STI), Tuberculosis (TB), Malaria transmission and cancer through research;strengthenlocal research capacity through training and technology transfers andimprove patient care capacity and delivery. It mainly operates from Kamuzu Central Hospital, Bwaila Hospital, Area 18, 25 and Kawale Health Centres. Over the years, its operations have expanded to cover health facilities in the Central West Zone including Lilongwe, Dedza, Kasungu, Ntcheu, Dowa, Mchinji and Salima. Find us for more information at www.id.unc.edu/malawi

    GSK one of the worlds leading research-based pharmaceutical and healthcare companies is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.

    Cautionary statement regarding forward-looking statementsGSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D Risk factors in the companys Annual Report on Form 20-F for 2014.

    PATH is the leader in global health innovation. An international non-profit organization, we save lives and improve health, especially among women and children. We accelerate innovation across five platformsvaccines, drugs, diagnostics, devices, and system and service innovationsthat harness our entrepreneurial insight, scientific and public health expertise, and passion for health equity. By mobilizing partners around the world, we take innovation to scale, working alongside countries primarily in Africa and Asia to tackle their greatest health needs. Together, we deliver measurable results that disrupt the cycle of poor health. Learn more at www.path.org.

    The PATH Malaria Vaccine Initiative (MVI) is a global program established at PATH through an initial grant from the Bill & Melinda Gates Foundation. MVIs mission is to accelerate the development of malaria vaccines and catalyze timely access in endemic countries. MVIs vision is a world free from malaria. For more information, please visitwww.malariavaccine.org.

    1 Intention to Treat (ITT) analysis, for this statistical reference and those that follow2 Burkina Faso, Gabon, Ghana, Kenya, Malawi, Mozambique, and Tanzania

    CONTACT INFO FOR MEDIA CONTACTS

    Malawi Media enquiries: Tapiwa Tembo +265 (0) 881589725 (Malawi) Portia Kamthunzi +265 (0) 999553034 (Malawi) Francis Martinson +265 (0) 888838388 (Malawi) Nelecy Chome +265 (0) 888338631 (Malawi)GSK enquiries: UK Media enquiries: David Mawdsley +44 (0) 20 8047 5502 (London) Simon Steel +44 (0) 20 8047 5502 (London) David Daley +44 (0) 20 8047 5502 (London) Catherine Hartley +44 (0) 20 8047 5502 (London) Sarah Spencer +44 (0) 20 8047 5502 (London) Claire Brough +44 (0) 20 8047 5502 (London) US Media enquiries: Sarah Alspach +1 202 715 1048 (Washington, DC) Mary Anne Rhyne +1 919 483 0492 (North Carolina) Melinda Stubbee +1 919 483 2510 (North Carolina) JenniLigday +1 202 715 1049 (Washington, DC) Karen Hagens +1 919 483 2863 (North Carolina) Analyst/Investor enquiries: ZibaShamsi +44 (0) 20 8047 5543 (London) Tom Curry + 1 215 751 5419 (Philadelphia) Gary Davies +44 (0) 20 8047 5503 (London) James Dodwell +44 (0) 20 8047 2406 (London) Jeff McLaughlin +1 215 751 7002 (Philadelphia)

    All PATH Malaria Vaccine Initiative (MVI) media enquiries: Ellen Wilson at +1 301 280 5723 or [email protected]

    PRESS RELEASEMalaria vaccine candidate hasdemonstratedefficacy over 3-4 years of follow-up

    Final results from Phase III trialsuggest substantial public health benefitscould be provided by the RTS,S malaria vaccine candidate in endemic regions in sub-Saharan Africa

    Vaccine efficacy enhanced by administration of a booster dose