GSK today announced that its Respiratory Syncytial Virus (RSV) candidate vaccines for maternal immunisation (GSK3888550A) and older adults (GSK3844766A) were well-tolerated and highly immunogenic in Phase I/II clinical studies. The data were presented virtually at the ID Week Congress. RSV is a leading cause of respiratory infections such as bronchiolitis (inflammation and congestion of the small airways or bronchioles of the lung) and pneumonia (an inflammatory condition of the lung small air sacs or alveoli) in infants and older adults. It is estimated to cause about 3 million hospitalisations of children under 5 year of age globally^[1], and 177,000 hospitalisations of older people in the US alone^[2]. Both candidate vaccines contain a recombinant subunit pre-fusion RSV antigen (RSVPreF3) which is believed to trigger the required immune response. The vaccine for older adults also includes GSK?s proprietary AS01 adjuvant system[3]?to boost the immune response as this population tends to show weaker immune response to vaccination than younger adults. The vaccine candidate for older adults was first tested in 48 healthy adults (18-40 years old) and then in 1,005 healthy older adults (60-80 years old) with different dosages of antigen and adjuvant compared with a placebo. The interim data 1-month post-immunisation show that:

• the candidate vaccine elicited a robust humoral and cellular immunity compared with baseline
• a close to 10 times increase of protective antibodies (RSVPreF3 IgG and RSV-A neutralising antibodies) was induced in the vaccinated group
• importantly, the cellular immunity (RSVPreF3-specific CD4+ T-cells) of the vaccinated older adults was boosted to reach similar range to that observed in the younger adults after vaccination with the non-adjuvanted formulation, despite the initial lower baseline level observed in older adults compared with young adults.

The maternal RSV candidate vaccine was tested with 3 different doses compared with placebo in 502 healthy non-pregnant women over monthly visits (Day 8, Day 31 and Day 91 post immunisation). The data show that, compared with baseline:

• the investigational vaccine was able to rapidly boost the pre-existing immunity at all dose levels, leading to high levels of protective neutralising antibodies
• at Day 8, a 14-fold increase in RSV-A and RSV-B neutralising antibodies titers was observed.

These two vaccines are part of a tailored, portfolio approach GSK is pursuing with three RSV candidate vaccines ? maternal, paediatric and older adults ? using different novel technologies aiming to help protect the populations most impacted: infants and older adults. All three candidate vaccines have received FDA fast-track designation. Emmanuel Hanon, Senior Vice-President and Head of Vaccines R&D, said: ?RSV is an infectious disease that can have a very serious impact on families and societies. We are delighted to see these positive results confirming our approach to develop dedicated vaccines building on the strategic use of our platform technologies for the populations most at risk from RSV infections ? young infants and older adults. Our portfolio strategy takes into account the unique needs of the immune system of these vulnerable populations and we look forward to progressing these assets to Phase III trials to evaluate their potential efficacy?. Vaccines for RSV prevention could lead to significant reductions in disease, doctor?s visits, and hospitalisations in infants, toddlers, and older adults, thus having the potential for a significant benefit to individual health in the most vulnerable populations as well as a positive impact on the burden and costs of healthcare systems around the world. Based on available data and engagement with regulators, Phase III studies for both older adults and maternal RSV candidate vaccines are in preparation and on-track to start in the coming months, while the Phase I/II (in RSV-seronegative infants) and Phase II (in RSV-seropositive infants) studies with the paediatric RSV candidate vaccine are ongoing. Phase I/II safety and immunogenicity data on the paediatric RSV candidate vaccine in RSV-seropositive infants will be presented at European Society for Paediatric Infectious Diseases (ESPID) on 26-29 October 2020. About GSK?s RSV candidate vaccine for older adults?(GSK3844766A) The Phase I/II study investigates the safety, reactogenicity and immune response of GSK?s RSV candidate vaccine? in older adults aged 60 to 80 (NCT03814590). This candidate vaccine contains GSK?s proprietary AS01 adjuvant, which is also used in GSK?s shingles vaccine. The safety, reactogenicity and immune responses (humoral and cellular-mediated) were first assessed in 48 healthy adults aged 18?40 years who were vaccinated with either 30, 60 or 120 ?g dose level of RSVPreF3 non-adjuvanted vaccine or placebo. Following favourable safety outcomes, 1005 adults aged 60?80 years were randomised in a 2-step staggered manner to receive 1 of the 9 RSV vaccine formulations containing either 30, 60 or 120 ?g dose level of RSVPreF3, non-adjuvanted or adjuvanted with AS01_E?or AS01_B, or placebo. Interim data presented at ID Week show that within one-month post-immunisation, the adjuvanted candidate vaccine has been well tolerated with no safety concerns identified. The most frequently reported adverse events were pain at injection site, fatigue and headache. Moreover, data 1-month post-immunisation show that the candidate vaccine elicited a robust humoral and cellular immunity compared with baseline:

• High levels of RSVPreF3 IgG antibodies (geometric mean antibody concentrations were 8.4?13.5 for the 18-40 year old vaccinees, and 7.2?12.8 fold-higher in the 60?80-year-old vaccinees) and RSV-A neutralising antibodies (geometric mean antibody titers were 7.5?13.7 in the 18?40 year old vaccinees, and 5.6?9.9 fold-higher in 60?80-year-old vaccinees) were induced in all vaccinated groups.
• Before vaccination, deficiency of RSVPreF3-specific T-cells (hypothesised to help promote viral clearance) was observed in older adults compared to younger adults. After vaccination, a robust RSVPreF3 CD4+ T-cells response in older adults had been boosted to reach a similar range than the one observed in younger adults, with significantly higher immune response in the groups who received the adjuvanted formulation.

About GSK?s maternal RSV candidate vaccine (GSK3888550A) The goal of this candidate vaccine is to prevent RSV-associated lower respiratory tract infections in infants during the first months of life by transfer of maternal antibodies ? an approach based on GSK?s strong expertise in maternal immunisation acquired through pertussis and flu vaccine programmes. The polyclonal nature of the humoral response boosted by this vaccine could potentially offer broad protection across a large number of RSV strains and addressing the potential issue of virus escape mutation. Maternal immunisation could help to protect infants too young to be immunised from RSV-associated infections in their first months of life ? when they are the most vulnerable ? without any medical intervention required thanks to the passive transmission of neutralising antibodies from the vaccinated mother to the unborn child in the last weeks of pregnancy. In this Phase I/II study (NCT03674177), 502 healthy non-pregnant women received 1 dose of either 30, 60 or 120 ?g of recombinant protein-based RSVPreF3 or placebo. The safety, reactogenicity and immunogenicity was monitored for 6 months. The data 1-month post-immunisation show that all vaccine dose levels were well-tolerated, with no safety concerns identified: the most frequently reported solicited adverse events were minor and included pain at injection site and headache. Moreover, the data show that the candidate vaccine elicited a rapid and persistent immune response in all RSVPreF3 groups. The immune response peaked at Day 8 with a 14-fold increase in neutralising RSV-A and RSV-B titers from baseline. The neutralising titers declined over time but a >6-fold increase was still maintained at Day 91. Anti-RSVPreF3 IgG antibodies were boosted substantially in all groups with geometric mean concentrations of anti-RSVPreF3 IgG antibody (= 12-fold at Day 8 and = 6-fold until Day 91 vs baseline). The 60 and 120 ?g dose levels of RSVPreF3 were more immunogenic than the 30 ?g formulation. Safety and immunogenicity data from the first time in pregnant women study will be presented in the first half of 2021. The data currently available provide the confidence to advance to late stage clinical work. ?About respiratory syncytial virus Globally, there are an estimated 33 million cases of RSV annually in children less than 5 years of age, with about 3 million hospitalised and approximately 120,000 dying each year from complications associated with the infection. Nearly half of these pediatric hospitalisations and deaths occur in infants less than 6 months of age^[4]. According to the Centers for Disease Control and Prevention, virtually all children in the US get an RSV infection by the time they are 2 years old and one to two out of every 100 children younger than 6 months of age with RSV infection may need to be hospitalised^[5]. It also represents a significant health threat for older adults, with an estimated 177,000 hospitalisations and 14,000 deaths associated with RSV infections occurring in the US alone^[6]. Without robust surveillance systems in several countries, global data on the burden of RSV in older adults is either lacking or likely to underestimate its significance. As global population ages, morbidity and mortality of respiratory infections including RSV to be steadily increasing. About GSK GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit?www.gsk.com. Cautionary statement regarding forward-looking statements GSK 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 company's Annual Report on Form 20-F for 2019 and as set out in GSK?s ?Principal risks and uncertainties? section of the Q2 Results and any impacts of the COVID-19 pandemic. References [1]?Shi? T. et al,?Lancet. 2017;390:946?58 [2]?https://www.cdc.gov/features/rsv/index.html [3]?The GSK proprietary AS01 adjuvant system contains QS-21 Stimulon^TM?adjuvant licensed from Agenus Inc. (NASDAQ: AGEN) [4]?Shi? T. et al, Lancet. 2017;390:946?58 [5]?CDC - https://www.cdc.gov/rsv/high-risk/infants-young-children.html [6]?CDC - https://www.cdc.gov/features/rsv/