Good day, everyone, and welcome to GSK's RSV Investor Call. My name is Deborah, and I'm your event manager. I would like to advise all parties the conference is being recorded. And now initially, I will hand on to Sarah Elton Farr, Global Head of Investor Relations. Sarah, please go ahead.
Thank you.
Thank you, Deborah. Good morning and good afternoon. Thank you for joining us to discuss the data presented at IDWeek on our RSV vaccine candidates for older adults and maternal immunization. You can access the slides we are going to use for this presentation on the Investor section of GSK's website under Speeches and Presentations. I would ask you to please review our cautionary statement on Page 2.
Also, please note that as we are in closed period and have Q3 results next week, we will not be answering any questions on the performance of the business. And now, I'll hand over to Doctor. Hal Barron, Chief Scientific Officer and President of R&D at GSK.
Thank you, Sarah, and thank you, everyone, for joining this call to talk through the encouraging data on the R and D presented at IV Reek. Joining me on the call, we have Doctor. Emmanuel Hammond, who leads our Vaccines R and D Organization and we also have Roger Connor, the President of GSK Vaccines, who will frame up the evolving landscape within RSV vaccines and how we think our candidate vaccine sits within this. With that, I'll make a few introductory comments and then turn it over to Manuel. At Q3, I spoke to you about 3 new vaccine candidates starting Phase III studies.
2 of them are for RSV. The first is for older adults, which is a very large and growing population. In the U. S. Alone, there are an estimated 70,000,000 people aged 60 and above.
The second RSV vaccine is for pregnant women to help pass protective antibodies to newborn infants, which in the United States represents approximately 4,000,000 women per year and globally more than 130,000,000 women per year. You'll see from the data that we share with you today that these vaccine candidates are well tolerated and have demonstrated a strong immune response, giving us confidence in the data and our decision to advance these programs into pivotal studies. Turning to Slide 4. As we have outlined in the past, a TF Care approach to R and D is based on the multiplier effect of science times technology times culture. We define this as strengthening our R and D pipeline by focusing on science related to the immune system, the use of human genetics and the application of advanced technologies such as vaccines, functional genomics, machine learning and cell therapy.
As you can see on Slide 5, our focus on immunology and these advanced technologies has resulted in a world class infectious disease portfolio, which includes 27 therapies in development, of which 18 are vaccines, and this accounts for around a half of our entire pipeline. The medicines and vaccines we are developing will treat or prevent HIV, COVID, urinary tract infections, hepatitis B and many other infections to read. This pipeline complements our existing marketed portfolio of more than 20 infectious disease therapy that together delivered almost $17,000,000,000 in revenue for GSK in 2019. And I mentioned this when I showed this slide of our Q2 results, but I think it's worth repeating that analogous to the declared war on cancer, which has resulted in a marked increase in investment by the pharma biotech sector on discovery and developing important medicines for cancer patients, we're optimistic that the world's experience with COVID may lead to an increased focus on the importance and value of developing new medicines and vaccines to treat and prevent infectious diseases. And with that set up, let me tell you why we're excited about the potential for our RSV vaccine candidates.
Moving to Slide 6. RSV is a very common respiratory virus. This infection causes acute bronchiolitis, which can lead to respiratory distress and hospitalization and even death, and it is the leading cause of hospitalization in infants under the age of 1. In addition, RSV is an important pathogen in the elderly and in high risk adults. Although pediatricians are keenly aware that RSV may cause serious illness in the patients, most internists are less familiar with the morbidity and even mortality associated with the virus in patients over 60.
Given the lack of treatment options, this lack of awareness is understandable. In older adults, the infection can cause pneumonia, which can lead to hospitalization and it's observed that the 1 year mortality following RSV infection in such population may be as high as 25% for these unfortunate people. In the older results, RSV is estimated to cause 177,000 hospitalizations and as many as 14,000 deaths per year in the U. S. Alone.
So given the significant unmet medical need and the high build on health care system, we're excited that we have 2 RSV vaccine candidates about to enter Phase II development. So with that now, let me hand it over the discussion to Doctor. Vanish Khan.
Thank you, Al. Welcome, everybody. So my name is Emmanuel Rano. Most of the people call me Emmanuel. And I'm responsible for the vaccine at an epiphytran in GSK.
Before getting into the specifics of our LNV candidate vaccine and the data that was presented at Ivy Week, I would first like to talk a little about our vaccine R and D strategy. At GxK, we are looking for the multiplier effects between science, technology and culture. To design and deliver groundbreaking vaccines with, for example, the strategic life cycle management of the Shingrix vaccine as well as our Menelitis franchise. With key new product assets in our RSV franchise or with our desire to enter new fields of vaccinology, specifically therapeutic vaccines and vaccines that target antimicrobial resistance. We do this by leveraging our portfolio of technology platforms, which is literally a toolbox with the goal of addressing unmet need and improving vaccine efficacy, making manufacturing simpler and faster and speeding up development time lines.
And this approach is underpinned by special mindset and culture where we take smart risks, we ensure single points of accountability for key decisions, and we attract and retain the best talent leveraging our presence in key geographic locations. Now on Slide 9. I believe that one of our key competitive advantage at the GS platforms, the toolbox I was mentioning earlier. Over the last 20 years, we have been investing strategically to deliver this rich portfolio. We are the leading company in adjuvant technology, and we have a strong position in adenovirus vector as well as in bio conjugation.
We are also investing heavily in messenger RNA with our SAM platform, self amplifying messenger RNA, and with our recent QURVAC partnership. Both of these platforms are highly complementary. All this means that we can uniquely select the right platform or the right combination of platform to deliver high efficacy vaccines that we can develop at pace and manufacture efficiently. Slide 10 shows the GSK vaccine pipeline. It is color coded.
New products are shown in blue, strategic lifecycle management in orange, and global health assets in green. We have added a special category in green of 3 COVID-nineteen collaborations that are at clinical phase. When looking at this pipeline, you can see the broad application of our adjuvant technology impacting all areas from life cycle management to discovery. And our pipeline is making good progress. In August, we started the Phase III of our pentavalent meningitis vaccine, which combines Bexsero, the market leading meningitis B vaccine, with Menviro, our vaccine for ACWY meningitis strain.
We have also started the Phase III study for Staph vaccine, which is a great example of platform combination. The IL-one adjuvant and the bio conjugation platform have been combined to deliver a unique formulation. For COVID-nineteen, we now have 3 clinical stage collaboration leveraging our pandemic achievement, which we believe has the potential to deliver strong and long lasting immunity, which is really important for the at risk population. With this collaboration, we have to provide an effective solution at scale. We have announced we will manufacture 1,000,000,000 of doses of the adjuvant in 2021.
The preclinical data for these assets we have in house so far are excellent, and clinical data will be available soon. Finally, and this will be the focus of the rest of my presentation, yesterday, we reported positive clinical trial results for 2 major assets, the RSV maternal and RSV oral adult vaccines, which are now progressing through stage gate and will move into Phase III. Let me now cover our approach to RSV vaccines. For 50 years, scientists have been trying to develop an RSV vaccine, but so far without success. It is only recently that science has progressed enough for us to have precise information about the identity of the antigen that should be considered to develop a successful vaccine.
We know now
the best antigen is likely to be the LHC fusion of F protein and that it needs to have the right confirmation to induce a sufficient quality and quantity of protective immunity. On the left of the Slide 12, you can see a three-dimensional representation of the post fusion conformation of the F protein. When used as a vaccine antigen, the F protein in its post fusion conformation only triggers a moderate increase in neutralizing antibody, a maximum of 3 fold. We believe that the reason for this is that it does not display the most potent neutralizing epitope, which are displayed on the pre F confirmation of the protein shown in red and orange on the right end of the slide. If a pre fusion confirmation of the antigen disease in the vaccine, it has been shown by the NIH actually first that it can boost neutralizing antibody by up to 15 times.
And this is exactly the antigen that GSK has selected. Now it is really important to highlight that the response induced by a vaccine approach is polyclonal, and this is essential to get high level of protection against the virus and potentially reduce the risk of escaping some viruses. Both these factors, mainly vaccination, may have advantages over monoclonal approaches. The development of a portfolio of FMC vaccine is a major area of focus for us at GSK vaccine. Our maternal vaccine based on the perfusion antigen used alone is designed to protect babies during the 1st 6 months of life, during which 50 percent of hospitalization takes place.
The vaccine is given during the 3rd 3 months of pregnancy with the goal of protecting the baby from drugs through a passive polyclonal immunization. In addition, the vaccine might also offer protection for the mother. The pediatric vaccine aims to expand protection beyond 6 months up to 2 years by raising active immunity against RSV using an adeno factor and therefore addressing the remaining medical burden associated with RSV in chain 1. For the older adult vaccine, we have never written our adjuvant platform, IT01. In the same way as we did for the Shingrix vaccine, We know that the older adults are less responsive to vaccination due to an age related decline in immunity, specifically T cell response.
And this is why we have combined the pre AF antigen with the ISO-one adjuvant to create a vaccine designed specifically for that older age group. All three vaccines have been designated fast track by FDA. The pediatric vaccine is in Phase II and some data will be presented as I speak next week. The maternal and the older adult vaccine are on track to start Phase III in the coming months, and this is why the next part of the presentation will focus on these two assets. Now let me take you through the key data from the Phase III trial of the maternal vaccine quality data analyzing immunogenicity and tolerability.
We enrolled 500 non pregnant women who were divided into 4 groups. 1 group received placebo and 3 groups received the vaccine at different doses, 3060 and 120 micrograms. Now before going into the details of the results, let me give you a very important context. As you know, last year, Novavax shared disappointing Phase II results for their maternal vaccine, and it did not meet the primary endpoints. Despite this, an important learning was made for the whole field.
The data showed that with the vaccine able to boost neutralizing antibody by 3 folds, that efficacy was between 40 to 50% depending on the stability of the endpoint used for sick children. So these data give an important of the level of immunogenicity needed that may confer protection. On the Slide 16, for our maternal vaccine, we were actually impressed by the response observed. Up to a 14 fold increase in LSD neutralizing antibody using the 120 micro count dose, Clearly, this is well above the 3 fold impact delivered by the Novavax candidate. In addition, the response was neutralizing against RSV A subtype, but actually similar response were obtained for the RSV B subtype.
And we also observed strong persistence on this response. After 3 months, there was still a 6 fold increase above baseline natural immunity. In terms of safety, the vaccine was well tolerated at all doses, with the most frequent adverse events being pain at injection site and headache. There was no vaccine related safety concern.
So we
are thus very confident in our candidate vaccine, and OpRegulatory is expected to start within a few weeks with the first major result anticipated in the second half of twenty twenty two. Let me now go through the key data on immunogenicity and tolerability of the older adult vaccine candidate. On Slide 19, you can see that the trial enrolled more than 1,000 subjects. Part A involved young adults exposed to placebo or various doses of antigen 30, 60 and 120 micrograms. This was needed to assess the safety of the vaccine, but importantly, to also develop a benchmark.
Young adults do not develop severe disease and so that immune response can be used as a relevant benchmark to compare with the immune response of older adults. I will come back to this. Part B of the trial exposed other avenues to either placebo or 1 of 3 different doses level of antigen that were combined with 2 different dose level of adjuvant. Please note that IL-1b is the adjuvant used in shrinkage and IL-1e is the lower dose version of the same adjuvant optimized for tolerability. And today, I'm reporting data 1 month after the first dose, data following the 2nd dose, and any subsequent analysis will be shared in due process.
On Slide 20, I'm showing you both the antibody response on the left and the T cell response on the right. If we look at the antibody response first, it is worth noting that after the LNG season, people who have had healthy disease generally have around a 4 fold increase in antibodies. So we set the bar in a clinical trial with a 6 fold increase as a minimum target. And you can see the results are very clear. Using 100 and 20 micrograms of antigen, we get from 8 to 9.9 fold increase in neutralizing antibody.
For the T cell response, because of the work on adjuvant and vaccines like Shingrix that we have done over the last 20 years, we have acquired a lot of experience in assessing T cell immunity. The graph on the right represents the distribution of the T cell response in each group before and after vaccination. And please note, these are medium, upper quarter and lower quarter distribution. And this graph shows the statistically significant impact of the ISO 1 formulations on the distribution of T cell response in vaccinated individuals. Both doses of ISO 1 were specifically superior to the non adjuvant formulation, which actually is in line with our expectation in this population.
So when assessing the overall data, including tolerability, we concluded that combining the ISO-1E formulation with the 120 microgram of our preS antigen is the optimal formulation for the oloravent vaccine. Now the next critical question is, is that immune response sufficient to give incremental efficacy and efficacy for older athletes? And the answer to this question actually to answer this question, it is important to look at the benchmark we measured in young adults. This is on the Slide 21. For the antibody response, on the left of the Slide 21, it's pretty clear that vaccination stimulates the immunodial response in older adults to reach a similar level of neutralizing antibody to young adults.
On the right hand side of the graph, looking at the T cell response, and I want to draw your attention to the fact that the pre existing T cell level in older adults before vaccination are much lower than the one you can observe in young adults prior to vaccination. And actually, this might explain the increased susceptibility of ozorabine to severe infection. Now for lowering vaccination, the level of T cells in ozorabine is well above the pre existing level in young adults and is approaching the post vaccination response of the same young adult population. I think this is pretty exciting data to see after only one dose. From a safety perspective, the first dose was well tolerated across the different doses.
The most frequent adverse events were pain in injection site, fatigue and headache with a trend for a slightly higher rate using the IL-two-1b, a different higher dose of a different formulation. There was no vaccine related safety concern. And so combining all the data, we are very confident in our candidate vaccine and are in discussion now with regulators and on track to start of Phase III within few months. The first major regions should be available during the second half of 2022. I will now hand over to Roger Collin.
Thank you, Vinu, and hello, everyone. I have to say we are really excited about the opportunity for our RSV vaccine, given the severe unmet need in both older adults and babies and the very encouraging data that we have generated on our candidates. And we've been working hard to accelerate the progression of these programs and believe that they really have significant potential. In particular, I'm excited about our older adult assets because of the scale of the opportunity and the encouraging data that we are seeing on immune response from the vaccine formulations containing our proven adjuvant technology platform AS01, the same platform used in our Shingrix vaccine. We're also very encouraged by the Phase III results and look forward to seeing how these assets are going to perform in their pivotal studies.
On Slide 24, we wanted to summarize the overall older adult opportunity. Hal mentioned earlier, RSV creates significant and widespread health burden in older adults. We have the opportunity here to introduce a vaccine to help protect 70,000,000 older adults in the U. S. Alone and 100 of millions more around the world from a common, a burdensome respiratory virus that can lead to pneumonia and other complications.
I think a really important point is that 2 thirds of older adults in the U. S. Receive vaccines regularly to prevent flu and pneumococcal disease. So this is a population of health conscious individuals and we have a particular expertise here with tremendous consumer insights having successfully launched Shingrix in this older adult population. Plus, we shouldn't forget GSK as a flu franchise that had a strong track record of successful execution and expansion in these years and there are a number of similarities between flu and RSV from an epidemiological perspective.
So bottom line, an older adult vaccine for RSV represents a meaningful commercial opportunity with multi $1,000,000,000 potential. And we believe we have the opportunity to deliver a potentially 1st in class and best in class differentiated asset. This belief is based on the knowledge we have about our adjuvant system that has delivered unprecedented efficacy in Shingrix for the same target population. So, we are very excited to invest in the Phase 3 program and we're on track with our plan to start early next year. If I move to the maternal vaccine shown on Slide 25, And the burden of RSV is also really significant in infants, and we believe the best way to protect them up to the age of 6 months is through vaccination.
Now the opportunity here is the annual birth cohort, which is about 4,000,000 in the U. S. And 1,000,000 babies more around the world. A key point here is that children are almost guaranteed to get RSV by the age of 2. It is the leading cause of hospitalization in infants less than 1 year of age and the burden is most pronounced in the youngest of infants where half of hospitalizations occur in the 1st 3 months of life.
Our maternal vaccine candidate is designed for routine administration during the 3rd trimester of pregnancy to protect the infant by conferring maternal antibodies to protect from birth through the 1st 6 months of life. Another benefit is that the mother may also be protected, which is good for her and potentially reduces the risk of transmission from mother's baby. Now with the GSK, we also have an existing portfolio of vaccines that are recommended for pregnant women with our pertussis and flu vaccines, and we estimate about half of moms to be in the U. S. Receive those recommended vaccines already.
So there's a partially built market in flu and an opportunity to expand the market size. Manu also highlighted that our RSV vaccines induce a polyclonal antibody response, which we believe could help address escaped mutant viruses, which is a benefit of our approach to preventing RSV infections. And by helping protect infants from birth, this program also really complements our pediatric RSV program designed for routine administration to help protect babies through to H2. So in summary, as we move to Slide 26, we're pleased to share the data sets for 2 of our RSV candidate vaccines we need today and look forward to initiating our Phase 3 studies with initial data expected for both of these large scale programs in the second half of 2022. The study times are best estimates and are dependent on how RSV infection circulate during pandemic lockdown, but we'll continue to keep you updated on the progress.
I want to finish by reminding you of the 3 key points I think we're making today. First, I think the opportunity is clear. There are currently no vaccines for RSV and there is a significant market potential, in particular for older adults, but also to protect babies and children. 2nd, at GSK, we have the chance to introduce a 1st in class and potentially best in class older adult vaccine with our candidate, which includes our ASO-one adjuvant system to boost the immune response. We view this as a potential multi $1,000,000,000 opportunity.
We're also competitive with our maternal vaccine, with the added advantage that we could add this to our existing portfolio of maternal vaccines for flu and pertussis. 3rd, the data we shared are compelling for both our older adult and maternal vaccine candidates and with other data we have in house support our decision to move to Phase III studies. And finally, remember that if you add in our pediatric vaccine, we are the only company to be developing a vaccine to treat all of the at risk populations for RSV. Now to deliver our RSV portfolio, we will continue to invest in our global manufacturing network that today already distributes almost 2,000,000 doses per day, expanding capacity to deliver the potential for these priority assets. And with that, the team here are ready to take your questions and I'll hand back over to the operator to start the Q and A.
Thanks very much.
Roger, thank you. We do straight away have the first question for you. It's from Jeffrey Porges from SVB Leerink. Thank you, Jeffrey. Go ahead.
Thank you very much and appreciate all the data and congratulations on the broad program. A few questions, if I may. First, what sort of efficacy do you believe is required in the different populations for approval of the vaccine against RSV? And could you disclose your specific endpoints, primary and secondary, for the 2 Phase 3s that you disclosed? Secondly, could you just give us a little bit more information about what you know about the consistency of the immune responses across different genotypes or subgroups of RSV specifically, probably NA1, ON1, VA genotypes.
And it is a virus that sort of has different forms circulating from year to year. And then lastly, given the importance of the pre F3 protein structure, why not consider an mRNA vaccine in this situation given the success that we then appear to be having in COVID?
Thanks very much for the question. Now we're not going to disclose detail on our Phase III program today, but maybe, I mean, you could take those questions in line with you.
Yes. So yes, as Roger said, indeed, we I'm sure you realize we have active discussions with the regulators to agree on the final design of our Phase 3. So I don't want to disclose exactly the level of efficacy. But obviously, we are targeting high level of efficacy. We have definitely a lot of we have accumulated a lot of data that allows us to really target high level of efficacy.
To your question related to different viruses circulating, yes, I mean, RSV is an RNA virus. So it's a virus that can slightly evolve. And this is the reason why it is so critical to target the virus with what we call a polyclonal response, so a response that target multiple neutralizing epitope on the antibody side, but at the same time using for the older adult and adjuvant to boost T cell immunity, we all know that T cell immunity can be also highly cross reactive. So this is definitely the strategy that we are pursuing, and this is why we are favoring a polyclonal approach in terms of in nature of immunity in the pregnant women for the babies as well as older habilics. In terms of messenger RNA, you're totally right in saying that this is definitely a disruptive technology that can accelerate the very initial phase of progression into clinical development.
Now once you have reached the Phase I clinical development plan, your timings are really dependent on actually the design of the Phase 3 and the season that needs to be hold out with the attack rate. So the technological advantage is less important here. But I want to acknowledge, the messenger ending technology is a very important technology. This is why GSK is heavily investing into the platform using actually 2 platforms, the self amplification messenger RNA platform as well as the messenger RNA platform from QVAC. And I want to remind you that we are just starting the Phase III, while those that consider to use messenger RNA against SABESD are just starting.
Thanks, Olivier. Next question, please.
Thank you. This is now Jo Walton from Credit Suisse. Thank you, Jo.
Hello. I wonder if you could just tell us a bit more about your degree of confidence in carrying to 6 months in terms of efficacy from on the maternal side? And if you were to, let's say, give birth in April and then you're in the Northern Hemisphere, so you've got the summer, it's really only months, say, 7 to 12 that you're going to experience the RSV. Are you confident that you will have your pediatric vaccine in place for that time point? And I just wonder if you could explain a little bit more again why you think a vaccine approach is better than a MAV approach in the maternal space?
Maybe I'll start with the comparison to MAV and maybe you can take the 6 month question as well. I think there's a number of factors to think about. First of all, vaccines being a proven method of protection at scale is where it start. From a maternal immunization, GSK knows and understands maternal immunization. And this is a well established method that utilizes that natural transmission of antibodies to the baby.
So I think making sure that we make the most of the already understood methods of transmission where we use it for flu and pertussis are very, very important. I think Manu mentioned it as well, a vaccine does potentially protect the mother as well, And that can help in terms of reduced transmission. And this is important in transmission potentially of RSV from mother to the child as well. And although Manu just mentioned it, I think this polyclonal point is important that we know that this Alvogen has been designed in this way to ensure that we get that polyclonal protection. And that has the potential to reduce this risk of those escaped mutant viruses, which does give us that potential for benefit over monoclonal.
That's what I would point out. Manu, on
the duration of protection? Yes. So it's very clear that we will definitely measure in our Phase III efficacy duration of fixed funds. So the data needs to be generated. But when looking at the full increase, we have up to 14 fold increase with the selected dosage.
We think actually we have pretty good margin versus the previous minimally benchmark that was reported in the previous year. And I'm not going to repeat the comparison between monoclonal and polyclonal, but I think this is really important. Finally, I also want to insist on the notion that it's in a way in terms of positioning going to be the combination of maternal and pediatric vaccine that will really ensure the protection beyond up to 2 years because actually, there is still 50% of the medical need that needs to be addressed after 6 months, and this is actually the proposal we have with the pediatric vaccines and an active immunization. Thanks, Helene.
And can I please just clarify your manufacturing capacity comment, in fact, 2 of them? So I believe you said, was it that you could make 1,000,000,000 doses of the adjuvant from a COVID perspective? And then could you clarify what sort of capacity you would have for RSV given that presumably if you're getting data in 2021 2022, you could need this in a relatively short time frame?
Yes, great question. I think it is, just to clarify, 1,000,000,000 doses our adjuvant available manufactured in 2021. So that is of the ASO3 adjuvant. And then for the capacity to support RSV, I won't give you the specific capacity number, but we are investing to support the significant ambition that we have for the vaccines. We go to the next question, please.
Thank you. Thank you. This is Tim Anderson from Wolfe Research. Thank you, Tim.
Hi. Two questions, please. I'm wondering how your trial powering and timing takes into account COVID dynamics. You note on Slide 26 that the timelines for readout depends on RSV infection circulation rates during the pandemic. So are you benchmarking against past infection rates that would not have been influenced by COVID?
Or has there been an adjustment made based on the best guess of what the impact of COVID could be? And then second question, with both vaccines, you say initial data expected in second half twenty twenty two that seem to suggest maybe that there will be some final data available at some later point. And I'm wondering if regulatory filings can be done on that initial data or is it going to be based on some later data? And if it's the latter, what is that later data? And what would be the filing time line for the vaccine?
Understood. So in fact, you may have indicated you're taking those.
Yes. Thanks. So it's very true that nowadays, COVID-nineteen, and it's not it's a well known phenomenon. When there is a pandemic, it actually takes the it occupies the space and the attack rate of other viruses can go down. And it is actually what is today being monitored in the field.
So first of all, this is something we are actively monitoring very, very closely to understand what is going to be the evolution. 2nd point is that, yes, obviously, both for the maternal MD and the older adult trial, we have been working on assumption adapted to the current knowledge we have on what could become the attack rate in the future, taking into consideration COVID-nineteen. So clearly, that has been taken into consideration. And thirdly, when we speak about initial data for the second half of twenty twenty two, this is definitely in the context of leveraging the data for a way that to remove. It is not an additional set of data of interest, but we will see you 2 years later with the rest of the data.
No, that's no debt.
So post that data point, we'd be assuming positive outcome and move through registration regulatory process. Exactly. And I understand. Maybe go to the next question.
Certainly. This is Andrew Baum from Citi. Thank you, Andrew.
Thank you. Three questions, please. Firstly, could you talk to how you perceive the benefit of cellular immunity, both for your COVID vaccine, but also for your RSV elderly vaccine. My recollection is that even aggravated protein subunit vaccines don't elicit effect of CD8 responses. Is that the concern here?
2nd, on manufacturing in relation to the RSV vaccine, how have you changed your mindset in terms of scale up given your experience with Shingrix where obviously demand significantly exceeds capacity? I'm just trying to gauge and put some context around the earlier comments. And then finally, in relation to your COVID-nineteen vaccine, could you clarify whether this will be a 1 shot or 2 shot vaccine? Many thanks.
Thanks, Andrew. Why don't you take the first T cell? Yes. So
as I explained during the presentation, because of the, let's say, unprecedented investment we have been doing in adjuvant platform over the last 20 years, we had to acquire a lot of knowledge on how do we measure this immunity? What does it mean, a specific increase? And I can only I can only I can definitely relate to the we actually made exactly the same level for Shingrix. With Shingrix, we were measuring 15 years ago antibody response and T3. And realized that with the adjuvant, we were able to actually impact the T cell immunity.
And we went into developed into Phase III, as you know, translating into very high level of efficacy. So T cell immunity in most of the viral infection plays a really important role. You are totally right mentioning CD4, CD8 T cells. Going back to ShieldWix, the ShieldWix vaccine does not induce any CD8 T cells. It actually mainly impacts the CD4 T cell component, and it's exactly the same that we observed for the RSV or the Haggard vaccine.
Finally, on the T cell response, I want again to point out the observation that we have consistently made between actually respiratory viruses where in older adults, both for influenza and now for RSV, you can see that the T cell immunity is significantly lower than what you observe in young adults. And that's actually what we think really that with the use of adjuvant and the ability to restore the system immunity to get to levels that are comparable to young adults, we are able, like 14 weeks actually, to get again an efficient response able to control the values. You're just talking about CD4, right? You're not seeing any effect on CD8, correct? Yes.
Yes. Okay. Maybe I'll take the next question, Andrew, which is on the manufacturing scale. Because of the significant opportunity we're seeing, we're already working on that manufacturing scale of plan and we'll be investing to support the assets. I think one thing to understand is that there's a subunit vaccine, which is a platform manufacturing process for us.
So we're not starting from scratch as well. So we're able to scale up what we already have. But as I mentioned, we are going to be investing behind this asset because we believe it is a significant opportunity for us. On the COVID vaccine, our belief is this is most likely our partnership with this is most likely to be a 2 dose vaccine. The data will obviously show that, but our working assumption is that it would be 2 dose.
Obviously, the ASO3 plays a very important role in these vaccines from a dose sparing perspective in terms of reducing that dose. And hopefully, the data will show the impact that it has both on the at risk populations, but then hopefully as well on duration of protection as well as our starting assumption is 2 dose. Thanks, Andrew. Maybe if we move on to the next question.
Certainly. Thank you. This is James Gordon from JPMorgan. Thank you, James.
Hello. Thanks for taking the questions. James Gordon from JPMorgan. Two questions, please. Firstly, can you contrast the 2, the RSV vaccine, the maternal and old adult population products to the respective Pfizer and J and J products, important differences there?
And the second question on the old adult product. Ultimately, if it is successful, would that be something that you could try and administer alongside Shingrix? And would you then have to develop a different combo? Because presumably, you can't give 2 adjuvanted products at the same time, so you'd have to fade it out? Or could you ultimately come up with some sort of combo product?
Mario, do you want to start with
the comparison with Pfizer and J and So Pfizer has developed an antigen that's categorized in the same place as the GSK antigen. It is a pre fusion conformation antigen. Pfizer has been recently communicating on their maternal vaccine. They also have another viral vaccine, presumably using the same antigen, but there is less information available on that. So I cannot say more.
G and G is following a completely different strategy. They use a Navinov vector vaccine to immunize individuals against RSV. So it's a very different technology. We have not done systematic comparison between what they do and what we are doing. What I can say is that we are pretty confident in the results that we have obtained on their consistency, the quality and the quantity of both antibodies and T cell immunity.
Whether we could combine the vaccine we see with, that's possible. This needs to be potentially included in future life cycle management opportunities. But I cannot comment more at this stage.
I think one thing that having Cengrix on the market gives us is that, obviously, a very strong understanding of the older adult vaccination market, the channels associated with those. I think it's too soon to tell whether coadministration, which Shingrix would be appropriate for RSP. As Manu mentioned, that's something we could look at. But we do think one of the differentiating factors here for GSK's RSV older adult vaccine is not just the adjuvant, but also our knowledge of that older adult space as well. The other point I'd make when comparing GSK maternal RSV to competitor activity is this point on portfolio should not be missed.
Again, our maternal understanding is very high. We know this space. We have trusted vaccine in this space as well, and we know again the population through which we would administer. So I think that's a significant benefit for GSK's portfolio here to have benefit to both vaccines that we're talking about. Thanks very much.
Let's move on to the next question.
Thank you. This is Laura Sutcliffe from UBS. Thank you, Laura.
Hello. Thank you. I was just wondering if you could share your thoughts on the time line and maybe probably the success for your vaccine in older infants. Do you think it's more challenging than the maternal and old cattle? Just
the pediatric vaccine? Yes. Productive success of the pediatric vaccine, maybe so first of all, this is one of the most challenging areas as 50 years ago, active immunization in children unfortunately led to, let's say, a completely opposite outcome of what you want to do with a vaccine. So we need to progress extremely carefully. Now the vaccines, the GSK has been developing is now being assessed in RSV seronegative children, which is the ultimate target population.
I think we are among the first doing that, and we will soon actually collect internally the data of this investigation. The probability of success of that asset remains, at this stage, low. But I want to say at the same time that all the preclinical investigation, including challenge trial that we will do in a CALF model, which is actually extremely close to the human situation, gave us extremely positive results, which give us hope that we can not only protect the 1st 6 months of life of these children with the polyclonal passive immunization, but we can expand beyond 2 years with this active immunization.
Thanks, Laura. Next question?
Certainly, it's Louise Seyerson from Redburn.
I've got question for Renee. And apologies if
I missed it. Just on the adjuvant, could you just elaborate on the difference between the B and E formulations, what it is that makes A potentially more tolerable than B and if these changes might sacrifice some of the adjuvant effects that were so powerful with Shingrix?
Yes. So IL-1b is the adjuvant that is used with Synryx. IS-1e is a lower dose of adjuvant. It's actually a 50% dosage of adjuvant. It's actually the same adjuvant that we have been using in other programs.
It is definitely optimized in terms of tolerability without actually losing the impact that we can have both on antibody response as well as in T cell immunity. And clearly, the ISO1 is slightly more powerful, but we actually get already a lot of the T cell benefits by using the ISO1e adjuvant. But at the end, it's exactly the same composition. It simply adds the strength, and I think it's important to mention that as we have already exposed 20,000,000 people with IAS1b, and so we are pretty comfortable on the safety database of this adjuvant.
Thanks, Louise. Next question, please.
Certainly, it's Graham Parry from Bank of America.
Great. Thanks for taking my questions. So first question on the old adult vaccine. Will you generate any data in reduction in hospitalization or mortality prior to the outcome of the Phase II data in 2022? So is there any chance of getting any of that data out of the Phase II?
Similarly, in terms of duration of response, timing of boosters, etcetera, do you think you'll have that ahead of the Phase III data? Or is that going to require longer term follow-up post the GH22 readout for the older adults? Then on the pediatric vaccine, could you just help us understand your thought process on timing for move to Phase III for that? What the hurdle is to move to Phase III? You're in Phase III in seronegative patients at the moment infants at the moment.
Is that going to be sufficient data for a pivotal trial? And the rationale, if you just explain it there, so using AAV, not the pre fusion design that you're using in the other
vaccines? Olivier, you okay? Yes. So again, I'm not going to severe on the lower respiratory tract infection, RHE. So we are not going to go after the mild symptoms of RHE.
We are going to go after the severe symptoms and the results must be primary endpoint and secondary endpoint that will collect the kind of severity, such as hospitalization, as you just mentioned. We believe it's really important as the cost effectiveness assessment of such vaccine needs absolutely this kind of data. I hope I captured all the questions. So I'm going there was a second question about the pediatric vaccine and the reason why we selected this one instead of using the pre S. So one of the findings that we made in actually 20 years of research in that specific field is that to actively immunize children against RSV, so beyond the positive protection caused by the mother, you absolutely need to prime T cells.
And there were different approach that were possible, and we found actually that the one that was the most effective in that specific AD group and that specific population was with using an adenovirus vector that is able not only to use T cell response as well as antibody response. And so the question was, what's going to be the next step? As I said, we will collect internally really important data either by the end of this year or early next year, and this definitely will be a critical readout conditioning the next steps for that asset.
Yes. And Graham, I think your middle question was on the duration of response to the overall. Is that right?
Yes, exactly. When will you know duration of response and timing of boosters?
So on that, basically, we need to keep all the options open with that vaccine. So obviously, our pivotal III efficacy that is going to assess the efficacy, the safety and the duration of protection. At the same time, we will also do the same on the immune response with, obviously, the vaccination and so on. So but again, we are speaking here again about the Phase III protocol design and so on. So we don't want to provide more information at this stage, but we'll come back to you as soon as we can.
Great. Thank you. And maybe one last question.
Certainly, thank you. And the final question today from Seamus Fernandez from Guggenheim. Thank you, Seamus.
Thanks very much for the question. So just a couple of questions on the market opportunity and the level of efficacy that you believe needs to be demonstrated in the adult type population. We've seen in the adult populations the utilization risk parameters that tends not to make for very successful market opportunity. So just wondering what the regulators, more so the government regulators like the ACIP, are likely to be looking for in an adult vaccine to achieve the $1,000,000,000 to $2,000,000,000 market opportunity that you're talking about? And then, as a follow-up question, with regard to your CoV-two strategy, you've collaborated on the CoV-two vaccine with your adjuvant, but also have the antibody effort alongside Vir.
Why not have a similar type dual approach? It just seems like with a monoclonal antibody, especially one that targets a conserved epitope, you could actually have a more targeted coverage of a pediatric patient population and potentially be easier for governments to reimburse. So just trying to get a better sense of that. So for the first question, you
will have to remind me, do the second question.
So for the first question,
very clear, but again, I'm not going to disclose you the level of efficacy we are targeting, but it's definitely in the upper quartile that we are targeting. It's very clear also that we are going to monitor the impact of the vaccine on the severe symptoms and consequence of the infection, such as hospitalization and possibly death. But in a Phase III of this design, it's unlikely we will be able to show difference in that. But potentially post marketing commitment might allow us to generate that. So we obviously also evaluate the efficacy of the vaccine for all that population that is at risk of developing severe infection, like the example of COPD patients or people treated with immunosuppressive drugs.
I want to remind everybody that 3 weeks, we just got the approval in your heart for immune compromised patient because again, thanks to the adjuvant and the impact of this immunity, it has the ability really to confirm and restore high level of protection even in these people that have a fragile immune response. Thanks.
And I just want to clarify. Your last question was why are you only going after vaccines and not after a mAb also for RSV? Is that correct?
Yes. You chose a certain strategy with CoV-two, CoV-two, which is a bit broader. Maybe it's just we were going after hospitalized patients with VIR, more so than prevention. But it does seem like a prevention strategy can perhaps offer a more obvious economic return to the governments that are going to be likely paying for it significantly around the globe. So it's just more a question of, yes, that choice.
I mean so first of all, I want to remind everybody, the DSK strategy actually is both. We have a vaccine strategy for prevention and to vaccinate the mass population, but there is also a monoclonal antibody that is being actually in Phase III today in partnership with the Beer Company. And that specific monoclonal antibody is being assessed in therapeutic setting. And I think maybe Al can complete potentially some prophylactic setting also.
But I think your question, Seamus, is about RSA though, wasn't it? Oh, we can. Correct?
Yes, correct.
Yes, yes. I think this is choice. And it's really around where we think we can make the biggest difference. And I won't go back to what we believe the differentiating factors are versus MABS. But again, in maternal, where we have the strength and this knowledge and an established method of delivery, we really believe in it.
And a key point is that vaccination through maternal protects the baby from day 0. For the moment, at birth, there is protection. We think that's not fully understood yet, and that could actually be an important differentiator as well. I think, Hal, is there anything you want to add on that particular question?
Well, I would just maybe add a couple of things just really quickly and we're out of time. But I think the difference, to some extent, reflects the fact that there's a lot of unknowns with COVID. The first point is that we're already starting to see evidence of resistance. And one of the things that made the GIR antibody so unique was that it was found from the reverse translation of the B cells from patients who were infected with the SARS CoV-one. And by identifying antibodies that would be both protective of that and COVID-nineteen, we believed and preclinical data supports this that the antibody would be binding an epitope that was highly conserved.
So I think when you have a situation where there's fitness advantages from different mutations, the polycline response may be enough, but we're already seeing resistance. So we're excited about the DIR antibody from that perspective. And as you said, the other big difference is the treatment of infected patients is a real opportunity for patients who where an antibody can add a unique thing from peers. So those are the two rationales for doing that with the company.
Great. Paul, thank you. And Seamus, thanks for the question. I think we're over time, folks. So I know there's probably more questions there.
If you can e mail those in through the IR team, we'll make sure that we get back to you. We hope you've enjoyed the session and you got a sense for our enthusiasm and excitement for this, we think, potentially very important set of vaccines. Enjoy the rest of your day. Take care and thanks very much.
Roger, everyone, all the speakers, thank you. That concludes your conference call for today. You may now disconnect. Thank you for joining and all take care.