All right. Okay. Wow! Yeah, it's really lovely to see such a crowded room. If I could ask for all of you, if you could just try to really put all your luggage a little bit under the chair or something. We just want to make sure that we have, we have aisle three. All right, good morning, good afternoon, and good evening to everyone. Welcome to the Sanofi Vaccines Investor Event, streaming live from London. Thank you for joining us and spending the next three hours with us to discuss our vaccines business. We have divided the event in two parts and have planned for a 20-minute break in between. If you're following us online, you can remain connected to the same Zoom link for both sessions. I would like to start off with two more housekeeping details.
First, you can find all the slides to this event on the Investors page of the IR section of the website at sanofi.com. Second, each part will conclude with a question and answer session. For that, we would like to ask you that you limit your questions to no more than two. We aim to take questions from the room here in London and also from those who are following us live on the webcast. If you do ask your question here, please identify yourself and use a microphone, and to participate via the webcast, please click the Raise Hand icon at the bottom of your screen. You will be notified when your line is open to ask a question, and at that time, please make sure you unmute your microphone.
Now, moving to slide two, I would like to remind you that information presented in this call contains forward-looking statements that involve known and unknown risks, uncertainties, and other factors that may cause actual results to differ materially. I refer you to our Form 20-F document on file with the SEC and also our Document d'Enregistrement Universel for a description of those risk factors. Now, let me take you briefly through the agenda for today. Paul Hudson, our Chief Executive Officer, will start with opening remarks and followed by Thomas Triomphe, Head of Vaccines Business Unit, who will share the Sanofi Vaccine strategy and the roadmap to deliver the guidance up to 2025, and our ambitions up to 2030, with a focus on our pipeline.
Thomas will be joined by his vaccines team to present an overview of the RSV and influenza franchises and the remarkable protection of our vaccine. This will be followed by the first Q&A session. After a short break in the second part, we will turn to our new growth areas. The vaccines team will present our pneumococcal and meningococcal programs and will share the work and progress on mRNA. For the new frontier section, we will welcome an external speaker, Dr. Geisler, Professor of Medicine and Epidemiology from the University of Alabama at Birmingham, who will provide his perspective on chlamydia and its consequences. The Sanofi vaccines team will present our chlamydia program as well as our acne program, we will close the event with a second Q&A session. With that, I would like to hand over the call to Paul.
Thank you. Well, thank you, Eva. One of our best forward-looking statements I've seen to date. Thank you to everybody for coming today. For those not in the room, thank you for connecting. It's a small room, and you can see the money has been invested in R&D. Thank you to the organizers for the fish and chips, to make me feel like it's home. Already a great start to the day. I'm really excited about what the team will share with you. I'm really excited for those that were studious enough to go back and look at 2021, and to read the transcript and to see whether what we said would come true, would come true, did actually come true. What we predicted would happen in the market, particularly with mRNA, whether it did in fact, turn out that way.
We like to believe it will. You should hold us accountable today for the comments that we made in 2021, therefore, you should have confidence in what we'll share with you today is also something bankable about what we think about the future. Please bear that in mind. We're straight. We believe in what we're saying. You should be able to bank it. They gave me four minutes to be able to tee up the entire company and the excitement. That's okay. We're making tremendous progress. You know, back in 2019, we highlighted some very important moments for the company. We said that in the future, we'll be $10 billion, greater than $10 billion for Dupixent. In fact, this year will be greater than $10 billion in a single calendar year. Incredible progress.
We raised eyebrows then, as you know. Now people raise their eyebrows when we don't announce an even bigger number, you know, we'll get to that, I'm sure, in good time. We said that we'd deliver an outstanding vaccine performance and high mid-single-digit growth. We did on R. We said that we'd prioritize the pipeline. We've redistributed more than EUR 2.7 billion to the pipeline and the business. Reallocated it over these few short years alone. Our transformation is underway. As it goes, we laid out sort of what we thought we would do. I mentioned some of this already, including the BD and M&A deals, the things we're exceptionally proud of, improving the profitability. More recently, I shared more publicly our commitment to AI.
While you may or may not be interested, while you may or may not understand AI, you should know at least that it unlocks significant productivity and resource reallocation opportunities for us in our company to go to the next level. It's perhaps the next big disruptor to be able to allow us to, A, target better in R&D, but to reallocate resources to do that more efficiently with a higher probability of success. It's not just optics, it's not just vanity, it's real work. 22,000 people out of our 91,000 have access to AI on a daily basis. 9,000 make better decisions, we believe, every day because of AI-enabled opportunities in our company.
I think we're the biggest AI at scale company outside of tech, anywhere in the world, any sector. We made tremendous progress, and whilst the finances are very important, the progress in the pipeline is probably something that I'm most proud of. Already three first-in-class, best-in-class launches this year. Can't remember the last time this great company did that. Beyfortus, strong AdCom, complete lockout, if you like. The guidelines pretty much in hand and the launch in time for the season. You know, we're really in a very strong place. Given that it's pioneering, the opportunity is pretty incredible what this team has done, and most of them are here, and they'll get their moment.
For ALTUVIIIO, we're off to a really strong start, and while you may or may not be interested, we'll share more through the quarters and later this year. We're ahead of where we thought we would be, and 10% of our patients are switched from Hemlibra. Again, that's remained consistent. That's interesting in itself, 'cause that tells us we have a slightly bigger opportunity than perhaps people thought. For TZIELD, which we managed just to put into our pocket nicely, not that long ago, we have a chance to do something significant to protect, beta cell function in type 1, and we have perhaps even a decade's worth of being on our own to do it. It's gonna do something very special. We'll earn the right.
You may have seen from the American Diabetes Association last weekend, they put it in the guidelines. If you've been around our industry a long time, you know it takes years to get into guidelines. They proactively put it into the guidelines. Not only are we doing some deals, we're doing them late, we're doing them in immunology, but we're doing them where they are appreciated by the specialists, the professions, those who care for patients. It's really extraordinary, actually. A couple of quick comments. If I draw your attention to tolebrutinib. Yeah, we still need to find a path forward, but we're really actively engaged, more that we'll share with you at Q2, probably. But the relapsing remitting data ahead of us, and not far behind that, we hope the secondary progressive data, which still leaves us differentiated.
Nobody else is doing a secondary progressive study. You know that. Nobody else probably will. It'll be us. While we don't get the chance to talk about it too often, you know, nothing has changed for us. There's still a tremendous belief and a real opportunity. Finally, for patisiran, which perhaps isn't even in people's models, for those that were less eagle-eyed and missed it, just a reminder of The Lancet article, the publication that showed you the seven-year extension. Buried within that was a small cohort of patients that went on to the new regime, which was a longer interval, lower dose. That's fascinating 'cause they were stable and had maintained efficacy. Will that be a leading indicator for what happens with the phase III readout?
If it is, then we've ended up with the longest interval for patisiran, and we've ended up with the most effective treatment in ALTUVIIIO and gene therapy. Step back, let's be honest, we could end up with the most important franchise in the entire industry in hemophilia. Maybe just go to, I think, the last slide, which is the pipeline news. You know, I sat with a bus tour that passed through Paris earlier this year, and I said, "How many readouts do we need, albeit they're at different stages, for you to believe that this company has started to reassert itself scientifically?" Remember, three first-in-class, best-in-class launches already. You know, the Purdue for PCSU will be later this year, I think, in November. You know, COPD, not many people gave us a prayer of pulling that off.
Of course, we get to disrupt. Not really everybody has fully understood that itepekimab is a different patient population entirely, and it's for the former smokers, and indeed had a positive pass-through of its interim. We're getting much closer to having the only two advanced therapies in COPD. Imagine that. Amlitelimab, we told you a long time ago that, you know, in the hope of launching early, something that would compete with Dupixent, that would perhaps be longer interval and have the same, if not better efficacy. Dupixent will grow until its very end of its life. It is foundational. You know from experience in biologics, that there is something extraordinary gonna happen, and the OX40 ligand for us, which we specifically chose and then developed, will now enter phase III. It's a different game.
Imagine SKYRIZI, but launched four or five years ago. This is what this will be for us. This is a big deal. frexalimab, which was presented at a conference, which not many of you, I think, attended, but the CD forty ligand approach, a greater than 90% lesion reduction, extraordinary efficacy, of course, going into phase III. Maybe we get to take on Akrivus in that setting, but with no downside risk on the side effects and safety. Really a moment for us. Lastly, I had the pleasure of being at the American Thoracic Society meeting for the DUPX COPD, the itepekimab IA, but also to talk about the IL-13/TSLP, which from the pheno data, as you know, puts us as perhaps the new efficacy bar in asthma.
Nanobody out of the Ablynx agreement or acquisition. Really could be totally extraordinary. We're advancing those. Then the very last one I mentioned, more like in passing, but really something pretty special is the oral TNF. You will see that we have a huge opportunity to do something. With the IRA like it is, and it's a small molecule, we will have to be brave enough to go forward in all the indications we think we can do, and we're brave enough. You will see what we do.
An extraordinary list, and I said to a bus tour in January, "You know, how many does it take for you to be excited?" They said, "If you get two or three of those, Paul, this means you're back." Of course, you know, by the time you run into some of those people, even at the lunch, they say, "Well, we really meant four or five." We're at five, and we have a couple of more here. I think just think about it from our perspective, more than 10 consecutive quarters of growth. Complete reallocation of resource to do what we need to do. Three first-in-class, best-in-class launches, five first and best data readouts, one or two more to come, and our last LOE of Aubagio this year. Imagine where this company has moved itself in a short period of time.
We're a different company, different management, different expectations, and we are making sure that by the end of this year, that people understand what a great proposition that we are. I'll leave you with this last comment, perhaps. We will launch three-five mega blockbusters between 2026 and the end of the decade. Potentially more than that, let's be honest, not including the three that we launched this year. Think about the scale of what we're doing and who we are without a bathtub that is leaking because we don't have the major LOEs that everybody else has. Different proposition for us, and this is all without the magic of vaccines. For the magic of vaccines, the magician himself, Thomas Triomphe. Thomas?
Thank you very much, Paul. Great to start bioscience, and definitely it deserves more than four minutes. Very glad you took them. Good morning. Good afternoon, everyone. It's my great pleasure to host our second vaccines investor event after the first one in December 2021. Today, the vaccines team is going to share with you the progress that we've made since Q4 2021, with a focus on our vaccines pipeline and our R&D engine is finally delivering. Very exciting journey to discover with you today. Let me start first with our ambition, exactly as it was laid out at our vaccines event in December 2021. The exact same slide. I'm delighted to share that we are well on track on every single of those three pillars that we identified back then. First, on our sales trajectory.
We delivered mid to high single-digit growth over the past two years, driven by our core franchises, well in line with our 2018, 2025 guidance. Second, definitely we're going to talk about it today, on mRNA. Only 24 months after the creation of our mRNA Center of Excellence, we have now established a competitive platform at the forefront of mRNA science. Our team will share with you today our clinical data, but also what we are doing in research, where we are pushing the boundary of this technology. Overall, I'm really thrilled by the progress made by the team over the past couple of years. Very short amount of time, great results.
Lastly, in the next three hours, we are going to deep dive into our exciting pipeline and share with you how innovative products can really address unmet medical needs all over the vaccine space and change the lives of millions of people. Before we look into our future, let's reflect for a moment where we are on the execution of our Play to Win roadmap. Over the past three years, this organization went through a massive transformation, and I've been impressed day after day by the energy, by the passion that our employees have put in together to make sure that we deliver tangible results. You can see on this slide some of our main achievements along the four pillars of our Play to Win strategy.
Just to name a few, when it comes to focus on growth, I was before mentioning the first two years, we actually delivered an 8% CAGR on our top line since 2018, well in line with our guidance, with two of our vaccines reaching blockbuster status. Our innovation engine is delivering very strongly, with Beyfortus already licensed in not one, two, three, but 32 countries, and ready to launch for 2023 season. On accelerated efficiencies, we have improved significantly the vaccines business profitability by six percentage points between 2018 and 2022. On reinventing how we work every single day, you know very well that we strive to create a unique culture at Sanofi, an environment where everyone, every employee, can bring his best or her best self at work.
I'm proud to see that in this unique environment, two years after the acquisition of Translate Bio, more than 90% of our mRNA experts have embraced that culture and chose to continue to work with us. Put simply, great progress on the execution of our roadmap. In the past two years, the vaccines R&D organization has also been through a major transformation of its own under the leadership of Jean-François Toussaint. Instead of me, maybe Jean-François, can you tell us more about that transformation?
Yeah, sure. Thank you. Thank you very much, Thomas. Before going there, I got to say that I still have a hard time believing that I joined your team only two years ago, because we have done so much already together. It's really an exciting journey, and thanks for the trust here. Of course, today, we're going to share many new data. You have seen that in the deck. Before that, let me say a few words about the major transformation of our R&D organization. You saw it, our transformation was based on three pillars, and it was designed to reinforce and to modernize the key enablers for us to win in vaccines. First, we continue to strengthen our capabilities in immunology and in antigen design.
On that front, I'm very pleased to share with you that actually we've scaled up and validated further MIMIC. MIMIC is our proprietary technology that recapitulate the immune system of humans just in a tube. I'm also excited by the progress that we've made in antigen design. I'm sure that you have heard many people questioning the ability of mRNA to express bacterial antigens. Not only we never doubted it, but actually we've done it, and we're going to show a couple of examples today later in the day. The second pillar of our transformation is about vaccines platform. You know, we invested massively in mRNA two years ago, first, with the creation of our mRNA Center of Excellence, then by welcoming Frank and our Tebayo colleagues within the Sanofi Vaccines R&D organization.
I'll cover that in a minute, the very exciting progress we've made, but what is important at this stage for you to remember is that Sanofi has a deep expertise in multiple vaccine technologies, and that we use the best platform for each given target. This will obviously, come through, the day when you will see the progress that we have made across our pipeline. The third pillar of our transformation is our renewed research and discovery pipeline, expanding into new diseases. More than ever, we are convinced that viral and bacterial infection trigger or accelerate chronic diseases. While we have initiated multiple program in this area, we're going to share with you today the significant progress we've made on acne and Chlamydia vaccines. Along with the transformation, we have also successfully rebuilt and advanced our vaccine pipeline, showing strong execution across all development stages.
We have seen the approval of three new products. Of course, before this, our first and best-in-class product for the prevention of RSV in infants. We have seen our COVID beta booster vaccine that was registered in Europe. We have also seen our Chinese version of VaxigripTetra, so our first quadrivalent influenza vaccine made in China for China. We obviously also moved significantly the early pipeline. By the end of this year, we'll have progressed six new programs into phase I/II. These include programs on flu, on RSV, on acne, also a meningitis pentavalent vaccine. Last but not least, our ambition is very clear and very realistic. It's actually to bring at least five new programs into pivotal trial by 2025.
Of course, a significant part of our early pipeline relies on the mRNA technology. It takes a team to do that. We are very proud of the scientists, but also the technologies that we have attracted in the mRNA Center of Excellence, including the Translate Bio people that have been working in mRNA for more than 10 years. We obviously complemented the skills with employee coming from Sanofi, also from diverse external groups. Among them, we attracted several top-notch experts in AI and machine learning that have already developed proprietary generative modeling for mRNA design and LNP design. On the technological front, you will see that later today, we are very pleased and proud to see that our first generation of mRNA already has a competitive profile. We don't want to stop there. We have anticipated it.
Our stated ambition is to develop the next generation mRNA. That's why we kept innovating, bringing as many as five lipids in clinical trials. Likewise, we have identified 4 mRNA enhancement features, and we also progressed very significantly on thermostability, going beyond nine months of stability at 4 degrees in a liquid formulation. Finally, the journey was also very exciting when it went to execution and the deployment of mRNA across the pipeline. We pivoted to modify the mRNA and validate it clinically, everything, the pivot, the GMP, and the clinic in nine months. In 2022, we also initiated no less than seven clinical trials based on mRNA. I hope you will agree with me that we are really on a winning track here. Now back to you.
Thanks a lot.
What I like a lot, the at least five in phase III by 2025. Very impressive acceleration indeed, Jean-Paul, so I thank you very much. When developing new vaccines, our scientists can now choose from 9 distinct platforms, probably the largest number in the industry. While it all starts with R&D, let me remind everyone that our vaccine business is also built on very strong foundations, reliably supplying massive number of doses all over the world every single year, generating convincing evidence that support the cost effectiveness of our product and the best recommendations, and a strong commercial workforce dedicated to vaccines. It may seem obvious on this slide, but we have seen recently various players in this industry, some new ones, failing on one or two of these elements.
Mastering these end-to-end capabilities is exactly what ensures that the vaccines that we discover in the lab will actually get used and do protect people. On the next few slides, I'd like to share with you and take a moment to really look at how we operate at Sanofi Vaccines. More specifically, our societal commitments are embedded into our business decisions every single day. You can see on this slide the four pillars of the Sanofi CSR strategy: affordable access, R&D for unmet needs, planet care, and in and beyond the workplace. Today, I've selected to share two cases that I believe do exemplify how ESG influences the choices that we are making in terms of vaccine development. First, a case under the affordable access pillar, and another one under the planet care pillar.
We rarely discuss with financial investors, especially our traveler and Olympic franchise, that includes vaccines against rabies, hepatitis A, typhoid fever, yellow fever, probably because these vaccines do not play into the EUR 1 billion market. Those vaccines are of utmost importance, addressing diseases mostly prevalent in low and middle-income countries. Have a look at yellow fever. Despite spending millions of dollars every single year in attempting to decrease the population of mosquitoes, the ones that transmit, sorry, the yellow fever virus, these mosquito populations and the yellow fever cases continue to increase every single year. Global warming is just making things worse. Vaccination is now regarded as being the most important means to help prevent those outbreaks. Sanofi is one of the key few companies to supply yellow fever vaccine.
We've been partnering with UNICEF and with other players for decades now, ensuring supply and readiness to respond to outbreaks. We are committed into this fight, and from an R&D standpoint, we continue to invest in yellow fever. We want to develop the next generation yellow fever vaccine that will replace the current two yellow fever vaccines that we have in our portfolio. I'm glad to report today, only on this slide, that the recent phase II results on our new yellow fever vaccine are very positive, and we are moving the program immediately to phase III. From an operational standpoint, on top of that, of course, replacing two yellow fever vaccines from a previous generation with 1 single new yellow fever vaccine will clearly rationalize our manufacturing footprint and simplify our operations.
Last but not least, you know that our new yellow fever vaccine will of course be embedded into our global access plan. Turning to planet care, on our second example, at Sanofi, we are constantly working to optimize the environment performance of our products. You have seen that we have decided to make sure that all new vaccines will be eco-designed by 2025. Concretely, what does this mean? For decades now, the standard packaging for syringe presentation was to provide those syringes into a plastic blister. Plastic takes hundreds of years to degrade, can break down in microplastics, contaminate the food chain, harm human health. Reducing plastic use is critical. We can help protect the environment and reduce the impact of the plastic pollution. We want to do our part.
This is why we decided we target to reach 100% blister-free packaging by 2027, even if it means potentially accelerating our industrial CapEx. We went on our way. By the end of 2023, 40% of our syringes will be plastic blister-free, while of course, 100% of our vial presentation already is. Moving away from plastic is not just for us. It's also about making sure that we set up the right standard, as we do believe that many countries around the planet will start adding into their vaccine standards this requirement, that high request for non-plastic containing packaging going forward, and we'll be at the forefront of it. Now, let's come back to our vaccines pipeline to wrap up this introduction.
At our Vaccines Day in 2021, we shared early information about our pipeline with many early stage trials that were going on at that time. As explained by Jean-François before, we have transformed the R&D organization in this company, enabling us to move fast and progress at speed. Today, we're going to share with you some results. That's how about the 12 key areas that you see here highlighted in this big area. We will actually start with a deep dive into RSV in the middle of the chart. We receive calls right now on RSV, I can see. Where we are the only company to offer protection to infants, to toddlers, and to other adults, with specific products developed with three different technologies that are best suited to deliver the targeted results, the targeted profile product that we have. We'll go to influenza.
We have a comprehensive mRNA program focusing on next generation vaccine to not just, not just be a me too, but actually improve versus current standard of care. Bill will lead us there. We will then turn to our exciting entry into multi-billion pneumococcal field. With a strong PCV21 phase II data, I'm sure you have seen it this morning, and how we are also building in parallel a best-in-class meningitis franchise. Lastly, we're going to uncover the progress that we made in the search of novel vaccines in the uncharted territory of acne and Chlamydia. Let's move on to the RSV section. We received the calls, it means we need to get there. I'd like to welcome Kimberly Tutwiler, our Global Head of RSV Franchise. Kimberly, floor is yours.
All right. Good afternoon. Good morning. I'm Kimberly Tutwiler. I lead the Global RSV Franchise. I'm happy I'll be joined later by Jean-François, our Vaccines Head of R&D, and I'm really happy to have a chance to talk with all of you about how we will deliver a best-in-class franchise for RSV. Since we last talked in 2021, a few things have happened. First, there was an unprecedented RSV season last year that unfortunately impacted many thousands of families around the world. Second, there are now a number of RSV immunizations coming to the market after decades of waiting. Finally, there's a lot of momentum for the first RSV immunization designed for all infants, and that's Beyfortus. We're excited to show you today the progress of Beyfortus and our entire RSV franchise, but most importantly, how it will benefit patients.
Our ambition is to lead in RSV across all critical target populations, and that ambition starts with Beyfortus in infants. This is a best-in-class immunization designed for all-infant protection, for infants in their first RSV season. We'll follow Beyfortus with RSV toddler. This is a first-in-class, live attenuated intranasal vaccine, and it's designed for toddlers in their second RSV season. Finally, our target in the older adult market is an mRNA combination vaccine with RSV, human metapneumovirus, and parainfluenza virus. You can see the total RSV market valued at just around EUR 8 billion, and our foundation of our RSV franchise starts in just a few months, during this upcoming season with Beyfortus, where the need for all infants is so critical. Let's start there, and let's start with what's new with this product.
We start with fantastic news, where the FDA Advisory Committee voted unanimously in favor of nirsevimab for infants in their first RSV season. They also voted in favor of nirsevimab for high-risk infants in their second season. This outcome reinforces the very strong efficacy and safety of nirsevimab. This is probably the most popular question I heard from many of you at lunch: What are our next steps? I can tell you, license and an ACIP recommendation anticipated in the coming weeks before the RSV season. The question, will we be ready to launch in 2023? The answer is yes, we will. We had more good news recently for Beyfortus from our results in the HARMONIE study, where its strong efficacy was confirmed in the real-world setting. You may remember the study, we discussed it in 2021.
This is a phase IIIb study. It was conducted in France, Germany, and here in the U.K. during this last RSV season in more than 8,000 infants, greater than or equal to 29 weeks of gestational age. We conducted the study for a few reasons. Certainly, to further reinforce the very strong data that we had in the pivotal phase III MELODY study. Also, to further enrich our hospitalization data. We wanted to demonstrate as well the implementation of Beyfortus in the real-world setting. Finally, we wanted to confirm the safety profile in a large population. You'll see the design of the study on this slide. Infants were randomized and allocated to receive either Beyfortus or no intervention during the first and only visit of this trial, and then they were followed up each month electronically throughout the season.
These results were presented recently at the ESPGHAN Congress. Let's take a look at this data. Starting with safety, we see that Beyfortus has an excellent safety and tolerability profile. You can see that the percentage of adverse events is similar to no intervention, and there are no serious adverse events that are determined to be related to Beyfortus. These results are consistent with what's been seen in our previous studies. The big question you probably want to know is: What about the efficacy? Let's take a look at that. This is absolutely exciting. Beyfortus demonstrated an impressive 83% reduction of hospitalizations due to RSV LRTI. Given that RSV is the leading cause of hospitalization in infants, this efficacy is so important for healthcare providers, but even more so for infants and their families.
These results are also consistent with what's been demonstrated by Beyfortus in other studies. Importantly, the efficacy here of Beyfortus in HARMONIE and in all of its studies is maintained for the entire RSV season. That's typically five months. That's critical for providing the protection that all infants need, and it's a massive advantage for Beyfortus. We know that in addition to efficacy, healthcare providers, health authorities, and payers, and maybe many of you, also want to know the impact of a product when it's implemented, primarily in the healthcare events that are prevented. Because there's a lot happening in this market with new entrants, it's important to evaluate that impact comparatively. Let's take a look at that data.
When we look at the real-life impact of nirsevimab, the result is that it's expected to prevent three times as many RSV events than a maternal vaccine. That's a significant impact, and it's due to its strong efficacy, expected higher immunization coverage rates, and the fact that nirsevimab is designed for all infants. Let me walk you through this slide and orient you with the data that's here. This slide shows the results of a model comparing nirsevimab and maternal immunization in the U.S., it leverages recent clinical trial data for each product, not from a head-to-head study. The assumptions that are here are sourced from the CDC, the University of Michigan Model on efficacy, health events, and RSV circulation, you may have seen this at the ACIP meeting last week.
The efficacy included here is at 5 months or greater to represent the duration of the RSV season, which for nirsevimab is 79.5%, and for maternal vaccine is 51.3%. The immunization coverage rates here are 80% for nirsevimab, aligned with the pediatric series, 50% for maternal immunization, aligned with current maternal immunization rates. You may notice there's something else that's exciting on this slide, and it's new, and that's new data. That's the efficacy against all-cause LRTI hospitalization. This is from the HARMONIE study, where nirsevimab demonstrated an impressive 58% reduction of all-cause LRTI hospitalization. It's significant. It's also unique, as only nirsevimab has been proven to impact this important endpoint.
I'll pause for a minute on this to be clear, because 58% is a very high number for an all-cause endpoint, so we are very excited to see this efficacy for Beyfortus. What does all this mean? The bottom line with all this data and all this information is this: Whether it's efficacy, the ability to protect all infants regardless of the month they're born, or immunization coverage rates, the data shows that nirsevimab is the more complete and, frankly, the better option to protect all infants. As I mentioned earlier, we are ready to launch in the 2023 season, and stakeholders are fully engaged on this topic. We already have licenses in Europe and Canada and here in Great Britain, and we expect broad population programs in Spain and in France.
We expect, I mentioned earlier, the licensure and the ACIP recommendation coming soon in time for the RSV season in the U.S.. We're already preparing there with contracting and reimbursement milestones and implementation on track. If you saw the ACIP meeting last week, you also saw a high level of support and excitement for all infant protection, but also for nirsevimab from some of the comments that were shared. We also had exciting news recently outside of North America and Europe, in China, where Beyfortus has been granted priority review. Finally, a really important element, we're not waiting to produce doses. That's already underway, as you can see in this picture on this slide, and we expect to fulfill the demand for this first season.
Leading up to this launch, we've engaged with a lot of physicians and public health stakeholders, and most of them have had the same reflection. They've been waiting for decades for a solution for RSV that they could offer to the broad infant population, and that they've desperately needed something to stem the tide of the RSV season every year, as we were reminded last fall, when a universal health emergency was declared in the U.S. and hospital beds around the world were full of sick infants from RSV. This season, we'll have the opportunity to protect all infants for the very first time with Beyfortus.
We've been discussing Beyfortus, which addresses the need for RSV protection in the first season, and I could talk about Beyfortus all day, but I'm going to move on, and I want to talk about the fact that the burden of RSV doesn't end there. RSV is a significant burden in the second season and beyond as well, impacting toddlers. The data you see on this slide on the left is the RSV burden in hospitalizations, pediatric office visits, and emergency room visits in infants six- 11 and 12- 23 months of age. On the right, the key diagnoses of GP visits in kids up to 5 years of age. What you see is that RSV is a core driver for bronchiolitis, antibiotic prescriptions, respiratory, and acute respiratory disease.
While we certainly hear the most about the burden of RSV to the youngest infants in the first season, and that's where it's the highest, the truth is that burden continues into the second season and needs to be addressed. The good news is we have a solution here, and Jean-François will tell us about the exciting assets we have to finish the job, which is to protect toddlers in their second RSV season, and then as well, to protect older adults with our respiratory combination vaccine. Jean-François?
Thanks, Kimberly, congratulations again on the outstanding ACIP outcome vote. Every outcome vote, that's brilliant. Starting with toddlers, as the first of the two program I will cover, it's very important for you to understand that the needs, as Kimberly explained, but also the immunization opportunities are quite different in toddlers versus infant. In toddlers, we actually have some time in between the first and the second season to come with an active immunization, an immunization that will mount an active immune response in the toddler. We plan to do it with a unique vaccine approach that is based on the live attenuated virus that will be given intranasally.
This candidate, because it's given intranasally, is expected to protect both the upper but also the lower respiratory tract, cutting visit to the GP, to the emergency unit, cutting hospitalization, but also potentially impacting transmission as well. The vaccine that we use is being rationally designed by the NIH to remain immunogenic while offering an optimal safety profile. Here is how we see it working in practice. Let's take the example of a baby born in the U.S. in June, for example, this cute toddler at the top of this slide. If she is born in June, she will receive Beyfortus at the age of three-four months, she will be protected for the whole season.
At the end of the first RSV season, when she turns nine- 10 months, she will be offered two doses of our RSV toddler vaccine. That will protect her for the second RSV season. As you can see, combining nirsevimab and our RSV toddler vaccine is expected to offer a continued protection of all infants across the whole first few seasons and the first few years of life. Here is how we have developed this product. Following a phase I safety dose escalation step that I'm now going to show you today, we have enrolled toddlers six- 18 months of age and administered them two doses of either a low dose or a high dose of the vaccine candidate. We've measured endpoints that are pretty classical for a phase I, so, safety, immunogenicity, and vaccine response rate.
Let's start with the safety. Actually, there is really not much to be seen here. We are very pleased with the safety profile of this vaccine candidate, which was similar to the placebo, whatever the dose that was tested. We have defined vaccine response rate as a composite endpoint based on immunological response, but also the detection of the live attenuated virus replicating at day seven. As you can see from this graph, the difference between the two doses was marginal. That's extremely important because that gives us some space to develop this product, to define its potency, but also to define its shelf life. The difference between a single dose and the two-dose regimen was also fairly limited.
At the end, if you look closely at the data, it's still the two-dose schedule that offered the most attractive profile, with a very good 93% vaccine response rate. We looked at immunogenicity, and we're equally pleased to see that both formulations induced a very robust immune response. The way the data are presented here is actually a classical reverse cumulative curves, where you have on the X-axis, the neutralizing antibody titers, and on the Y-axis, the percentage of volunteers. What is key here is that the two formulations induce a nice shift of the curve to the right, reflecting a substantial increase of neutralizing antibody titers in most volunteers.
Overall, we are very encouraged by the data gathered in this program, and we are actively preparing for pivotal phase III trial, and we expect to start pivotal phase III trial in the first half of 2024. If this reads positively in phase III, there is no doubt that we will deliver the first-in-class RSV vaccine for toddlers, and that we will set a high bar for competitors that are at least two years behind us. Shifting gears now, let's go to our RSV older adult program. As you know, you have been following the field, and there have been quite a few or a couple actually, of RSV vaccines approved recently. Our ambition at Sanofi goes beyond that, as we aim to come with a vaccine combination that will protect against multiple viruses of the same family, and it's important of the same family.
Why? Because we believe that the winning combination for older adults need to include viruses that are associated with a high medical burden, that's obvious, but also viruses that don't evolve over time, so that we can keep the vaccine composition stable year on year. If you look at the chart on this slide, you will see that a combination vaccine, including RSV, HMPV, standing for human metapneumovirus, and PIV, standing for parainfluenza virus. Such a combination vaccine will address a similar medical need as influenza vaccine. You remember December twenty-one, at least the one who were with us at that time, you remember that we had predicted that RSV vaccine for older adults would not need to be given every year. This is exactly what ACIP has confirmed last week.
We expect it will be the same for HMPV, the same for PIV, supporting again, why our combo vaccine combining RSV, HMPV and PIV is the one that makes sense. RSV is obviously a stepping stone of our program. end of last year, we initiated the phase I/II trials with multiple formulations in a small cohort of young adults, so adults below 60 years of age, and a larger cohort of adults above 60 years of age. We tested three dosages of mRNA and two different lipid nanoparticles. This was a classical phase I/II, where the objective were to assess safety and immunogenicity. Here again, we were very pleased with the profile of vaccine candidates, and we have identified the formulation that was both potent and well-tolerated. On the left part of this slide, you can see the reactogenicity.
Yes, the vaccine was extremely well-tolerated, with self-resolving adverse events of mild to moderate intensity and over short duration. On the right, you see that the vaccine was also very immunogenic, with an 11.5-fold increase in neutralizing antibody titers in the young adults and a 5.4-fold increase in the older adults. We believe this is particularly strong because remember, we have faced a very intense RSV season in the year that preceded our trial, and our trial was conducted in January, February. Our safety data show that we have room to increase further dose in older adults if we need to. Based on these results, we are very confident about moving forward a couple of combination vaccine formulations in a phase I/II trial by the end of this year.
Looking at the competitive environment now, we believe that our combo vaccine is a real potential to be a first-in-class. We expect that its superior medical value, combining these three viruses, superior medical value compared to RSV, will provide a more compelling case to recommending body, leading to a better recommendation than the one that was provided to GSK and Pfizer by the ACIP last week. Kimberly, would you like to wrap up this session for us, please?
Thank you, Jean-François. Hopefully you can tell we're really excited about our ambition to protect all targeted ages from RSV, and we're the only company to offer this. You'll see on this slide our strong portfolio of products and our next steps, and you'll see that we're advancing the development of our products in toddlers and older adults quickly, moving forward in the next few months. Our products, combined with our commercial expertise in introducing pediatric and adult immunizations, is what will secure our RSV leadership. If there's one thing that you should take away today about our RSV franchise, it's this: it's that first and best in class is what we will do, and that begins in a few short months in the infant market, where we will address a critical need with Beyfortus, and we will win for all infants and their families.
Thank you for your time today. I look forward to hearing your questions later. Now I'm happy to welcome Bill Averbeck to the stage to talk about our exciting flu franchise.
All right. Thank you, Kimberly. Well done. Hi, I'm Bill Averbeck. I'm the Head of our Flu franchise. Right before this event started, 1 of you came up to me and said, "Are you that guy that said flu is only 1 letter away from fun?" I said, "Yeah." He said, "You plan on saying that again today?" I said, "No." Peter, there you are. The next question was, "Anything else witty to say today?" I said, "Witty, no. Something? Sure." I was hoping this event would be on Friday because everybody knows you can't spell Friday without IR. However, this is on Thursday, so we can't spell Thursday without you, so thank you for coming to our event. That's the pity sigh that I was looking for. Yeah, I'm gonna stop before I get the hook. Why am I here?
Not just for bad jokes, but I am here actually to talk to you because I'm excited to speak to you today about why we believe we are uniquely positioned to win in flu by delivering on protection beyond flu and by designing vaccines specifically built for seasonal markets. The one thing I like to reinforce as we begin the flu section is the leadership that we hold in this market. We have been part of the flu ecosystem for over 70 years, and I'm happy to announce that reports of our demise have been greatly exaggerated. We have been, we are, and we will continue to be the leader in flu. We have a rich history in flu and have continued this leadership via the pioneering of the transition of quadrivalent vaccines beginning in 2014.
We've continuously driven the value of the flu market higher while maintaining our overall leadership position, reaching EUR 3 billion in annual sales. A cornerstone of this increased value is our differentiated product offering, with products like Fluzone High-Dose and Flublok. We have defined a new class of differentiated flu vaccines and now set a new benchmark of protection beyond flu as the standard of evaluating these vaccines. We will continue to lead this market through our pursuit of the next chapter in flu prevention with mRNA technology. We'll hear more about our progress with our flu program from Saranya. Before we get there, I want to take a second to remind us that this is not a technology story, but rather this is about preventing the most serious outcomes in the most vulnerable patients, regardless of the platform utilized.
As many of you may recall, in December of 2021, we made the point that mRNA vaccines would not have an immediate impact for the simple reasons that flu is not COVID, and that the vaccine profile, the pandemic vaccine profile, will significantly limit its uptake in a seasonal market. We stated that mRNA vaccines would only capture a fraction of this market by 2030. When we stated this position, I'm willing to bet some of you folks listening weren't so sure this is how things are going to play out. Since then, we have seen data that has only reinforced the reality that first-generation vaccines simply cannot deliver on the key success factors of this market.
We told you that the road to the first-generation mRNA vaccines will be long and difficult, and without significant improvements, they simply will not be commercially viable. Let me remind you of these three key success factors that have only been reinforced over the last 18 months. The first factor is protection beyond flu, and it remains the most important. Products must demonstrate improved efficacy and effectiveness when compared to a standard of care. Payers and providers demand consistent, strong data across endpoints that matter, like hospitalizations from pneumonia and cardiovascular complications. The second is tolerability. Products that are administered to hundreds of millions of patients each and every year must have an excellent tolerability profile to maintain a high level of patient acceptance. Lastly, administration.
The seasonal flu market requires certain elements of administration, such as having a liquid formulation in a prefilled syringe that can be stored in a refrigerator. These elements are a have to have to be successful in this market. What has changed in the last 18 months? I'll offer two points. One, protection beyond flu has been established as the true measurement of flu vaccine performance, and we have new data that shows Fluzone High-Dose has increased its leading position and continues to be the benchmark that all other products will be compared to. Secondly, we went out and spoke to both providers and consumers, and we have new market research that clearly reinforces that products with increased reactogenicity and limited thermostability will not be accepted by either providers or patients.... I'm not here to share our hopes or opinions.
I'm here to show you new data that clearly proves our position is correct. First-generation mRNA flu vaccines will not win. Let me start with protection beyond flu and Fluzone High-Dose. As you can see, delivering protection beyond flu to the older adult population has allowed Fluzone High-Dose to continue to be the strong and consistent market leader in the U.S., significantly contributing to us delivering about $1.7 billion overall in 2022. Demonstrating protection beyond flu was a key factor when the product was evaluated by the ACIP and led to their conclusion that Fluzone High-Dose has the most data for the most outcomes. As an organization, we are committed to continually add to this robust data package of Fluzone High-Dose.
We've set the bar for protection in this age group of Fluzone High-Dose, with data from 12 years and over 45 million patients. However, it's not just about the sheer volume of data, which is unparalleled, but it's also about the quality of this data. Randomization is such a critical element in study design that we are investing in novel ways to randomize large number of subjects to further prove the impact that Fluzone High-Dose has on a population in real-world settings. With DanFlu studies, we aim to measure the impact of Fluzone High-Dose versus standard-dose vaccines on protection beyond flu endpoints, like pneumonia and influenza hospitalizations. In our first study, creatively named DANFLU-1 , Fluzone High-Dose has showed an impressive 64% reduction in pneumonia and influenza hospitalizations versus standard-dose vaccines across 12,000 subjects.
Now we're aiming to further validate these results in DANFLU-2, where we randomize over 200,000 subjects to add to the unprecedented body of evidence that we have for Fluzone High-Dose. It's not just us saying this. The impact of Fluzone High-Dose has been recognized worldwide, with the recommendations or favorable reimbursement in over 10 key markets. The bottom line is that for older adults, the highest level of evidence of proven performance against flu-related complications is required, and only Fluzone High-Dose has demonstrated this across both randomized controlled trials and randomized real-world studies. Any product attempting to be commercially viable in this older adult segment has to replicate the sustained, well-documented performance to the same level as Fluzone High-Dose. Essentially, we will continue to raise this benchmark as others are trying to reach it. My second point is across tolerability and thermostability.
As you may recall, that second key success factor is tolerability, which is important for both older and younger adults, but a particular concern for younger adults where coverage rates are much lower. Flu vaccination rates have been increasing for years as a result of global efforts to build consumer confidence. Introducing a product with an unfavorable reaction profile risks upsetting this delicate balance. That's exactly what healthcare providers and consumers reinforced in recent market research. In fact, introducing a product with 3x the severe reactions versus the standard of care could decrease healthcare workers' willingness to administer by almost 70%. Even an increase in 2x in reactions will result in a decrease of up to 40%.
Consumers showed the same pattern, with again, an almost 70% decrease in willingness to accept the vaccine, with three times the severe reactions versus what they're currently accustomed to. The final key success factor is administration. Here again, a reminder of the delicate seasonal flu ecosystem that has been established over decades. This ecosystem was set up to maximize access at every opportunity, whether at the doctor's office, the pharmacy, the workplace, or drive-thru types of clinics. What these networks were not set up to do was manage ultra-cold change, like what we saw in the mRNA COVID vaccines. Not only does a pandemic profile introduce complexity, it again risks decreasing uptake, something made evident in our recent research with healthcare professionals.
We found that a lack of a refrigerator-stable flu vaccine lasting throughout the season could decrease healthcare workers' willingness to use it by 40%. Overall, we continue to maintain that the first-generation mRNA vaccine candidates will not be successful in the flu market, as they've not even come close to the proven protective patient benefits of Fluzone High-Dose and have significant work to do across reactogenicity and thermostability compared to any of the currently licensed flu vaccines. For mRNA vaccines to be relevant in this market, they will have to continue to evolve to a next generation of product designed for seasonal routine use. To further discuss our efforts in developing these next-generation products, I'd like to turn it over to Saranya to walk you through the progress we're making on our mRNA flu program. Saranya?
Good morning. Good afternoon. My name is Saranya Sridhar. I'm the Head of Translational Medicine, and it's my pleasure to be here today to share the progress on our mRNA flu program. Bill, thanks for the jokes, but also thank you for the target product profile that you've made very clear that we need to achieve for future influenza mRNA vaccines. Last year, we started 4 trials as part of our program, with quadrivalent hemagglutinin-based and neuraminidase-based vaccines. In our first three trials, we evaluated multiple formulations of a quadrivalent hemagglutinin-based mRNA vaccine, and in these trials, we tested three different lipid nanoparticles and different dosages.... We are very clear about the benchmark that mRNA flu vaccines have to meet, and therefore, in each trial, we compare them to the standard of care in each population.
Fluzone standard dose and Flublok in the young adults and Fluzone High-Dose in the older adults. We also started our first pilot trial with neuraminidase, a different antigen to hemagglutinin. We are adding this additional antigen because we have previously shown that neuraminidase antibodies play an important role in the superior efficacy of Fluzone High-Dose. We started a pilot trial to see whether mRNA vaccine candidate could induce antibody titers in the same range as Fluzone High-Dose. Let me share some data with you from these trials, which gives us confidence that we do have a very competitive mRNA platform. Let's start with the quadrivalent hemagglutinin-based trials, and here are the immunogenicity results from our lead lipid nanoparticle in the young adults. We present here very typical endpoints for flu.
On the left-hand graph, you can see the fold increase in antibody titers compared to the baseline, and on the right, you see the seroconversion rate. As you can see in the first two sets of columns representing the responses to the flu A strains, our mRNA vaccine, shown here in purple, induces a very strong immune response, trending superior to Fluzone standard dose and in the same range as Flublok for both endpoints. As reported with the other mRNA flu vaccine candidates, the immune response against flu B, shown in the last two sets of columns here, was trending lower than the standard of care vaccines. More evident when you compare to Flublok. The immune response we observe with our platform is very similar to that observed with other mRNA vaccines.
What that tells us is that improving on the standard of care, the minimum bar against which all mRNA vaccines need to be compared, is difficult. If we compare the data from our platform on the left to another mRNA candidate vaccine, we can see the same pattern of strong immune responses for the A strains and lower B strain responses. What that's suggesting to us is that low flu B responses are probably a class effect across mRNA platforms, and that we do need to find a more comprehensive solution to ensure a strong B strain performance year-on-year with mRNA. Now, as Bill mentioned earlier, reactogenicity is as important as immunogenicity. Let's look at our reactogenicity data compared to the competition. We measured the grade 3 local adverse reactions, shown here on the left, and the systemic adverse reactions on the right.
Our candidate performed better than reported with other mRNA vaccines. However, compared to Fluzone standard dose and Flublok, which wasn't associated with any grade three events in this trial, our mRNA vaccine was more reactogenic. While we're on the right track to improve tolerability of mRNA vaccines, we continue to work to bring them to the levels observed with standard-of-care vaccines. Taken together, I think the strong immune responses against the A strains, our platform's lower reactogenicity profile compared to the competition, confirms that we do have a competitive mRNA platform. As Frank will detail much later today, we will continue to evolve the platform in step with the competition to improve reactogenicity and tolerability and thermostability. Let us be clear that mRNA technology is only a means to deliver improved flu vaccines.
As we said in December 2021, the mRNA technology alone won't be sufficient to achieve these goals. Next couple of slides, I want to give you an update on the progress we've made on machine learning for better strain selection and on the inclusion of neuraminidase antigens. Let me first remind you of the concept of our innovative machine learning-based approach. As shown on the left-hand figure of this slide, every year, the WHO collaborating centers generate large data sets, leading to recommendation of the strains to include in the vaccine, which provides the coverage as indicated here by the small black circle. Despite the rigorous framework used, influenza is so unpredictable that new strains sometimes emerge right before or even within the season, as shown by the red cluster at the top of this graph, leading to suboptimal vaccine performance.
At our last Investor Day, we had shared how we designed algorithms to select strains offering a broader coverage, as shown here by the larger circle in blue. This has the potential to make vaccines more resilient against viral evolutions during the season. We also shared data from the clinical trials we had conducted with H3 strains that validated this approach. Today, we are pleased to share with you how we've extended this concept to H1 strains. As you can see on the right-hand side of this graph, machine learning strains, the solid lines, offer a stronger immune response against a broad panel of strains compared to the WHO-selected strains, the dotted lines. What this does is it brings us much closer to entering this improvement in our development pipeline. Let me finish with the data from the pilot...
Different doses of unmodified mRNA, encoding neuraminidase and compare it to Fluzone High-Dose. You know, we're very pleased with the data from this trial. These graphs show the response to neuraminidase with a fold rise in antibody titers on the left and seroconversion on the right. We know that the minimum bar to be used as a reference when including neuraminidase in your vaccine composition is Fluzone High-Dose, which contains about 2.5- 3x higher neuraminidase content than standard flu vaccine. Our mRNA neuraminidase vaccine met this benchmark, inducing antibody titers and seroconversion rates that are at least equal to those induced by Fluzone High-Dose. Of note, we also observed a good reactogenicity profile with this vaccine despite the use of unmodified mRNA. Bill, we've got through a lot of data here that underlines the strength of our flu portfolio.
Why don't you come up and summarize it for everyone?
Thank you, Saranya. Overall, we believe we're continued to be poised to win in flu. We are actively building next-generation flu vaccines, investigating multiple factors across multiple technologies, designed to deliver solutions for seasonal markets across the key factors that this type of market demands. We've made great progress on our mRNA flu vaccines, clearly closing the gap with our competitors. However, further work is required because even if it were to be licensed, this first generation of mRNA vaccine will not be commercially successful for all the reasons we outlined today. In the meantime, we are focused on expanding both Fluzone High-Dose and Flublok, as these products are the only two products that have proven a demonstrated performance of efficacy against the standard dose vaccine in randomized controlled trials.
In addition, Fluzone High-Dose has achieved a consistent demonstration of protection beyond flu for over 12 years. Having a clear path to developing the next generation flu vaccine while continuing to grow our current business, gives us that unique ability to continue to win in flu. Thank you very much.
Now we have around 20 minutes for our first Q&A session. I'd like to invite all our presenters back on stage, and we're going to start here in the room. Why don't we just start from the side if we start with, Florent. If you could please, wait for the mic, just identify yourself quickly, and then off we go.
Thank you very much. Florent Cespedes from Societe Generale . Question for Thomas. You usually, where you are guiding, you are cautious, but you are also ambitious. With a EUR 10 billion target for 2030, could you give us, share with us which are the plus and minus for the moving parts that could lead to a potential increase or maybe the challenges? Thank you.
Thanks a lot, Florent. Great question. It's all about the ambition. The way you phrase the question is very important. Yes, we're reasonably cautious, which I will translate as we say what we're going to do, and we do it, and we deliver it back to 2021 and 2023, but we're ambition. I think the important part on the ambition is greater or EUR 10 billion sales by 2030. Doesn't mean we are shooting for 10.00. How are we going to get there? Which is behind your question. We don't exactly provide numbers, we're not going to change our habit, an exact split product by product. I still need more, a few more quarterly earnings to get there one day.
Of course, if you think what we are seeing in the pipeline today and the data we have, it's going to be clearly more confident in what we are building in RSV. I think RSV is going to be great. I'm sure there might be some questions on it. Beyfortus is not an if, it's a now, it's a reality. RSV or the other, it's not about an RSV flu combo, and I'm happy to come back to this. It's about having the right RSV combo, and that creates a lot of certainty. Of course, you can talk about PCV21 and put a number, but when you don't have phase II data, it's different than when you have phase II data. All of this together is going to be greater or equal than EUR 10 billion.
If we go to Pete.
Thanks, Pete at Old City. Three quick ones. Paul, firstly for you, I've enjoyed your rousing call to arms comments at the start. With that in mind, if you do get a fair wind with the upcoming data readouts, just what's your appetite like to move midterm targets away from BOI and free cash flow to actually growth-based targets? Thomas, just, you've given us your revenue expectations. I realize you no longer disclose vaccines margins, just aspirationally, would the idea from a profitability perspective be to maintain already high levels, or can you do better? Lastly, one for you, Thomas: would you consider inorganic opportunities in adult RSV if opportunities came up? Is it very much about you want to go down the path of combination vaccines with, you know, non-evolving viruses?
Thank you.
You want me to start and both you. Okay, I'll start with the vaccines one. Profitability, well, you know, we don't provide any more specific targets, but the goal, it doesn't mean that the goal is to decrease profitability. You know our roadmap of Play to Win, three pillars, efficiency is the third one, efficiency is going to remain there. However, what I think is very exciting is that we have more and more proof points of the R&D delivering. Each time, our R&D philosophy is pretty simple, and I'm sure I'll come back to it today. It starts by looking what's the need in the marketplace. Therefore, what's the target profile we want to have? Therefore, what's the science requirement to get there? If we have the science, then we got to be there.
We are making good proof points on the science. For sure, we're going to keep investing in R&D science in vaccines, but of course, with the right level of efficiency. On the other part, inorganic opportunity, like everyone, we're looking into it. Needs to make sense, needs to fit with our commercial footprint, needs to fit with what we know and are able to do. When it comes, I think you had something specific in mind about our RSV older adult. It goes back to the philosophy, and that's why I started by that first. What's the need? The need, and that's exactly what you mentioned in December 2021. The need is to have the right respiratory combo that makes sense.
In December 2021, we said, "Okay, I understand, and I hear the hype, but we do believe, very humbly, that RSV flu combination vaccines will have a very low opportunity because RSV will not be an annual vaccination, because the RSV virus is very stable, which is not the case of flu." Turns out to be much more interesting when it's ACIP saying it than just Sanofi guys. I fully understand that part. We also said, and we'll talk about our combination, but same thing, they will have limited opportunities because the disease is going to shift, requirements, and this year are going to shift. The way we're looking at it is actually what you had in your question is, what's the need?
RSV-based combination that answer a multi-annual protection on stable respiratory viruses, HMPV, PIV are just in that space, and there are two problems for hospitalization of the elderly. If externally, to come back to your question, there was a great opportunity in that space, we would look into it. Right now, the science is very good in our camp, and we're going full speed on this one.
Thanks, Thomas, and thanks to the team. By the way, I don't often get a chance to say this up front during a session, but great job. Really strong. Rousing is what you said, right?
Yeah.
I think, we're getting ahead of ourselves to talk about the areas you want to go. You can see that moment, right? You can see it in our future, but I think my energy this morning or this afternoon, was more to try and help people understand that we've reached such an accumulation of positive news flow, that I'm not sure it's fully appreciated, calculated, included, and I think there's some work to do on that. When I feel like it's been properly included in the thinking of where we are, there's just too much for it to be ignored, then we can talk about how it's best to look longer term as a company.
Okay. We move to Graham.
Thanks. It's Graham Parry from Bank of America. Question on toddler RSV. What is the intended phase III trial design in terms of endpoints? What do you think you need to show in a phase III trial to stimulate some broad uptake there? Is it just lower respiratory tract disease? Is it hospitalization data that you're going to need to really get an ACIP recommendation there? Do you have any sort of sense of the size of the market there? Is this a pneumococcal size market, for example, in your minds, or is it something smaller? Second question on flu. Can you just clarify whether the quadrivalents that you've been showing us the data on today are already thermostable, and or is that still TBC in further development?
How do you intend to improve, B serotype immunogenicity? Thank you.
Great questions, very happy to have some RSV toddler questions. Jean-François, I give this one to you. RSV toddler endpoints, how do you see the clinical design? Maybe just on the marketplace, the size of the opportunity. Do we see it as a pneumococcal opportunity just for RSV toddler? No, it would be a lie if I ever think so. Why? Because it's not four shots, it's the burden of disease of RSV between one and five years of age, not IPD, invasive pneumococcal disease from birth. It's, you saw the market, it's a billion-plus marketplace. We're going to be first, best in class, I don't think there's going to be much competition at all with the product profile we have. It's, it's a potential blockbuster for sure, not a pneumococcal area.
Um, design-
I think the last question, Graham, I think we rather, in the interest of time-
Yes.
We park for the second half because we have some more.
You have the answer in the second half, and you can ask about thermostability. We're going to show you with Frank, what we're doing on mRNA thermostability.
Thank you, Thomas, and thank you, Graham, for the question. For sure, in RSV toddler, we're going to develop it as we have done for nirsevimab, meaning we're going to look at all the endpoints that matter from a public health point of view. It's clear that we are discussing all the endpoints with the regulatory agency, it's still early, but for sure, no doubt that we will have lower respiratory tract as an endpoint. Yes, we're going to look at upper respiratory tract because we believe there is a need there, and we believe that will be a differentiator for us compared to competition. Of course, these are two endpoints only that I'm sharing with you today. There will be others in the phase III or post-licensure. For sure, as nirsevimab-like documentation, I would say.
Matthew?
Thank you. It's Matthew Weston from Credit Suisse. Two RSV questions, if I can. The first, just on capacity. You made it clear that you felt you had capacity for the upcoming season. I realize it's a biologic, so very different from what we see with normal vaccine scalability. Can I just check that you don't see any issues in terms of multi-year scalability of supply for that product? Then secondly, just back to RSV toddler. I might be wrong, I thought the ACIP recommendation was a majority vote, that for high-risk patients, they could get nirsevimab in their second season. Other than the economics of being wholly owned versus not wholly owned, what's the advantage of going for all toddlers with a novel vaccine versus just sticking with nirsevimab in second season for high risk?
Thanks for the clarifying questions. I get to you, Kimberly, for the second question. The first one I can handle quickly. Supply, do we feel good? We feel very good. No issue on ramp up. We have a great partner that has strong manufacturing capabilities for monoclonal antibody. We're able to scale, and we feel very strong when we look at the next year. These are small compared to monoclonal antibody traditionally. Yes.
Sure. Good question for toddler. Nirsevimab, just to clarify, for high-risk babies in the second season. Why would we go for a toddler vaccine versus nirsevimab for all babies in the second season? Probably wouldn't make sense, one, from the total health economics of nirsevimab for all babies in the second season probably would not make a lot of sense. Would also say, remember, in the first season, we're giving the antibodies passively because babies are too vulnerable, too little to develop their own. The value of giving a live attenuated intranasal vaccine in the second season is they're going to build their own antibody response, and we hope that that's going to last a little bit of time because kids are at risk until age five. It's about sizing what is necessary based on the problem at hand.
When they're so little in the first season, they can't do this on their own. When they get to the second season, that's the right time to let them develop their own antibodies, and hopefully, those are going to last. That's a bit the rationale.
Just to clarify, Matt, also, the ACIP wording might be, or the FDA outcome wording might be a bit confusing. When they're talking babies at risk, it doesn't mean all the babies for the second season. It's a very, it's a very tiny proportion.
Okay. Louisa?
Thank you. Luisa Hector from Berenberg. Again, RSV questions, maybe the older adults this time. You didn't say a lot about the phase IIb, what is the reason for that trial rather than phase III? I think you mentioned possibly trying a higher dose, would you perhaps compare to the new vaccines that are launching now? If when we think about the mono or the combo RSV, is there a role perhaps to look at booster phase III there eventually, or would that be the focus being on the unvaccinated still? Thank you.
I like R&D creativity popping up. Great question on the second one. Jean-François, I give you the floor for those two questions. First one on the design of the next stage for RSV toddlers, and what about combo for the vaccination?
The reason why we designed the phase IIb is fairly simple. The reason is changing a little bit following the outcome of last week, the ACIP from last week. For sure, we are convinced we have a great vaccine, no doubt. We were fearing that actually the window to show the efficacy would wane. That's why we designed a phase IIb to show the efficacy against placebo before the vaccine is widely implemented. I must say now that Pfizer and GSK have received a pretty poor recommendation with a short decision making, we believe the uptake of the RSV or the other vaccine from GSK and Pfizer will be much slower than anticipated, now anticipated. That means the window might remain open longer.
We may demonstrate efficacy in the phase IIb and potentially in the phase III with the combo, which were the specific one. That's the reason for that trial, actually. You want me to?
The vaccination company.
Yeah. No, I think, I think it's a brilliant question. I love it. For sure, again, another set of data that was apparent last week is that when you revaccinate with a protein-based vaccine, you cannot boost, at least when you revaccinate after one year. This might be true for all the RSV vaccine, for all the others, or it might be a class effect of protein-based vaccine, in which case, our vaccine could have a profile for primary vaccination, but also a profile for booster dose. At the end, we expect that booster dose will be needed. You saw the efficacy dropping in RSV or the others. It's not that you will be immune for the rest of your life. The market will not disappear. You saw the efficacy waning, both with an adjuvanted vaccine and a non-adjuvanted vaccine.
Everybody will have to reboost at some point. That's our view.
If you need to boost after three- five years, and the market has been built by our dear colleagues, and if mRNA technology is the right one to boost, it will not be a bad spot to be in.
Peter?
Thank you. Peter Welford at Jefferies. Two questions. Firstly, just coming back to the RSV toddlers, just wondering, we've seen great antibody immunogenicity data many times before in RSV, and then phase III trials have failed. This is obviously intranasal. Any thoughts on doing a challenge by before you go into phase III, given, you know, given the route and given everything else? Equally, do you have to some extent, enrich for the one year and the two-year-old? I guess, what's the risk? You know, by the time you get four and five-year-old, their actual natural immunity mutes the response you're going to be able to get in a phase III trial when you're trying to actually show hard endpoints.
If I could just ask on flu, is the only way you can beat Fluzone or Flublok into the real endpoints to go with more antigens, more strains? I guess the question is, do you realistically think you can ever beat Fluzone High-Dose with just a quadrivalent mRNA vaccine? Is there any point?
Before we go to flu, RSV toddler, maybe explain a bit what we have in mind, challenge or no challenge, and how we do see, the product profile, because it could be used for toddlers, as the name says, but the intent is not to provide protection just for the second season. The idea would be to protect for more season without new doses of the RSV toddler product.
Challenge?
Yeah, challenge is usually something that you do when you are not sure that your vaccine will work in phase III, and you want to discharge the risk. If you don't have confidence, it's a reasonable option to consider. We are confident in the performance of our vaccine. It's building on decades of research at the NIH, that's why we believe with the safety, the immunogenicity, the vaccine response rate, the next logical way for us is go straight in phase III.
Two. One, maybe, Saranya, you want to take it?
I think that's a really interesting question. I mean, clearly, I think you're convinced, thankfully, that Fluzone High-Dose is a really high bar. That's the important message I think you should take away. You know, Fluzone High-Dose are very interesting. It's really an evolution of technology, and I think what you see in Fluzone High-Dose is a combination of different antigens. You do have hemagglutinin there, but you also have neuraminidase, and then, in fact, you have some other antigens like nuclear protein. I think you're right. It is a high bar to meet there, and that's why I think what we're trying to do in R&D is really look at multiple parallel approaches that include both neuraminidase, but also this machine learning approach, optimizing the B strain.
I think as we get the data next year about all these different approaches, I think we get a much better indication of where we need to go.
Okay, let's try to take one question from the webcast. If we could have David. David, can you hear us?
Yes, great. Can you hear me as well?
David from Leerink?
Yes. Can you hear me as well?
Are you unmuted?
All right. Can you hear me?
Yes. Fantastic.
Okay. Thank you very much. Thank you for the question. I have two. First, could you discuss your hypothesis why mRNA vaccines for flu underperform on the B strains consistently? Second, with respect to PCV21, if you could just comment on what happened with the adult phase II results. Thank you.
Okay, thanks. Let's park the PCV for the second one. We can come back to that. Yeah, let's talk about mRNA and the beta strains.
I'm sorry I may disappoint you a little bit there. We have a fairly good idea of what is happening. Of course, it's also a very highly competitive field. You have seen that our competitor have not really disclosed what they were working on to fix it. We are working on a couple of opportunities. We believe we have the solution in one of these streams, but we're not going to share that for the reason I mentioned.
Okay, thank you.
Thanks.
Bill would have given you the answer that, flu is not COVID. I.e., it's not an A population, but it has seen multiple strains of flu before, and therefore, the real specific range go is much more complicated. Science will tell the right pathway.
Okay, let's take one quick last one here in the room. If we have Simon, yeah, we have a second Q&A session also after the, after the second part.
Thank you. Simon Baker from Redburn. Just on going back to RSV, I'll just limit this to one question. On the hospitalization data, that's changed quite a bit since the December 2021 presentation. You said 177,000 this time. It was 105,000 last time. Is that just a different data source, or have things changed post-pandemic, and there's a bigger disease burden for RSV now?
Hospitalization. Kimberly, you want to take this one?
We continue to look for the best hospitalization data that we can find, right? We're always getting new sources because RSV is also a space where we're continuing to get more and more information through surveillance and through epidemiology. I think that's the first thing. I think the trend of what you see on the impact in hospitalization, both how much of it there is, and then the impact from a product perspective on what we can reduce, I don't think that's changed. I do think we have some new data sources that you're seeing, though, that's absolutely true.
Surveillance system of our commercial looking doing than we used to before.
When you look, you find.
We're going to go for a short break. For those that are following us online, we're going to shorten the break to 10 minutes. As planned, we're going to be back now at 3:40 P.M. Please stay on the same link. For those here in the room, we're just going to take a short bio break, get some air into the room. For the ladies, if you need to go, you have to go right and then immediately left. For the gents, if you need a restroom, just go straight past the elevators into the hall, and then it's on the right side. Let's see you all back again here with fresh air, hopefully, in 10 minutes. Thank you.
I would like to acknowledge the presence of SK CEO, Mr. Jeong, here with us today on the second row. We have a very productive partnership on this ambitious program, and we are sharing together this significant, promising investment. As a reminder, we are co-developing together our PCV21, SK is in charge of manufacturing and retains commercial rights in Korea, while we are leading the commercial launch globally. I'd like to come back on the medical improvement we are bringing by adding a 21st serotype to the standard of care. With our PCV21, we do have the opportunity to extend protection against pneumococcal disease and raise the bar by adding coverage. This matters. Additional serotype coverage matters in the PCV pediatric field. Indeed, there is still a significant residual burden of pneumococcal disease, especially in the pediatric segment.
As administration in the U.S. alone, residual disease accounts for 1,500 invasive pneumococcal disease cases, as well as 1.5 million cases of acute otitis media in the population less than five years old. Despite major progress, disease is still out there. Our additional serotype 9N, will provide an additional five-seven percentage points gain in IPD coverage across all ages. In addition, beyond direct protection to children, PCV vaccination offers a positive, indirect impact on the other age segment through herd protection, which does help reduce the residual burden of disease in the overall population. Now, let's hear from Jean-François on the exciting results from the phase II trial of our PCV21 vaccine. Jean-François, the floor is yours.
Thank you very much, Thomas. As you explained, we are focusing and accelerating on the pediatric segment. I'm going to share with you today the data observed in the pediatric trial. We designed our phase I/II trial, actually, to select the formulation that could be progressed into pivotal trial, and we tested multiple formulations, compared them to PCV13. PCV13 was obviously the standard of care at the time when we started the trial. The vaccine was tested in infants according to a classical schedule based on three administration, zero, at two, four, and six months of age, and then a booster between 12 and 15 months. The endpoints were very typical for phase II trials, so safety, reactogenicity, and immunogenicity, of course. For immunogenicity, please note that we have used the endpoints that are mandated by regulatory authorities for licensure.
These are the IgG concentration and the seroresponse rate post-dose three, as well as the IgG concentration, post-dose four. Let's have a look at the reactogenicity profile first, and here I'm showing only the lead formulation in purple. As you can see, the vaccine was very well tolerated, with similar level of local and systemic reactions compared to the PCV13. Let's deep dive in the fun part of this section and have a look at the immune response induced by our lead formulation. The graph on this slide, I acknowledge, are fairly complicated, so let me walk you through the data that they contain. First, it's important to note that this slide is focusing on the serotypes that are in common with PCV13.
The eight additional serotypes will be covered on the next slide. In each slide, the different lines represent different serotypes. Second, you see that the graph contains two sets of information. The purple dots represent our PCV21 vaccine candidate, whereas the gray dots are reported by our competitor with a PCV20 vaccine that was recently approved in the pediatric population. Third, I want to remind you that the data are expressed in relative value compared to PCV13. It's either as a concentration ratio or as a seroconversion rate difference. Now that we are all on the same page, or at least I hope that we are on the same page. If it's not the case, there is a break afterwards to discuss that. Let's have a look at the data.
The first graph here on the left part shows the strong immune response induced by our PCV21 vaccine candidate after the third dose. You will note that all the serotypes are in line with PCV20, but that we actually have a really favorable profile for serotypes 3, 5, and 23F. You know that serotype 3 is a critical one, so we are very pleased to see that our deliberate efforts to improve it are really paying off. The graph in the middle looks at the seroresponse rate post-dose 3, and the graph on the right represent the IgG concentration post-dose 4. Both of them show the same picture, and they confirm a favorable profile of a candidate compared to PCV20.
This slide now shows under the same format, the results that have been observed with the eight serotypes that are not contained in PCV13. Again, we were pleased to see that our vaccine induced a strong immune response with results in line or favorable with PCV20. If you combine these two slides together, I'm sure that you now understand why we're excited about this candidate and why we're excited about the way it compares to PCV20. We believe that this result that you just saw create a strong path for us into phase III and then to licensure. Let me share with you for the very first time, how we plan to stay ahead of the pack. Today with the PCV21, but also in future generation containing more than 21 components.
We actually introduce a new carrier to improve the performance of the four serotype, 1, 5, 15B, and 22F. We do that to improve performance, both performance, but also to avoid overloading the immune system with a CRM carrier. The graph on the right show that these four conjugates induced a strong immune response. As you have seen before, including this carrier did not increase the reactogenicity or the tolerability profile of a product. The last piece of exciting data with this product was gathered in an additional phase II trial, that was designed to support the interchangeability of our product with PCV13. We actually administered PCV21 or PCV13 to toddlers who had been primed with three doses of PCV13.
As you can see on the left graph, both candidates were equally capable of boosting the immune response primed by PCV13. As shown on the right graph, a single dose of our PCV21 candidate induced a strong immune response against the serotype not covered by PCV13. What does it mean in practice? It means that the baby will receive three dose of PCV13 or PCV20 in the future, would be eligible to receive our PCV21 vaccine as a fourth dose, making it easier for the practitioner to switch from one product to the other, while offering the benefit of the additional serotypes. I hope that you appreciate that we have developed an ambitious program, and that our phase II results have convinced you that we are really well positioned at Sanofi to deliver the first PCV vaccine covering more than 20 serotypes in infants.
Together with our excellent partner, SK bioscience, we will initiate the pivotal phase III trials in the first half of 2024. We will target a regulatory submission in 2027. If you look at the size of the market and you look at the profile of our product, we really believe that our PCV21 pediatric candidate will become a blockbuster, that very quickly after launch. As I said, we will not stop at 21. That's not the end of the race. We have already initiated the preclinical development of a higher valency product. Just summarizing it, if you put it all together, we are convinced that we can make a strong entry in the PCV market. We intend to remain highly competitive on the long run. Now let's move to meningitis, another exciting prevention area. Thomas, floor is yours.
Thank you, Jean-François. Now, meningitis. I am very excited to report that we are consolidating our leadership in meningitis with MenQuadfi. MenQuadfi is setting a new standard in the quadrivalent meningitis prevention space. Its best-in-class profile is defined by several features that do matter in the daily practice. First, a higher immune response against C, which we know is key in many markets that are switching from C standalone to ACWY and do not tolerate any compromises on C protection. Second, MenQuadfi is available in a fully liquid presentation that eases administration for the healthcare providers. Third, MenQuadfi age indication is broad, giving administration flexibility and ability to match multiple schedules in the U.S. and in the rest of the world. Lastly, we now have up to seven years persistence in different age groups, which is now documented in our label.
MenQuadfi is the U.S. market leader with more than 60% market share, and I am very happy to share that we now have converted all our U.S. customers from Menactra to MenQuadfi. Beyond the U.S., MenQuadfi is now registered in more than 53 countries, including all the major European countries and key international markets. Now, I'd like to share new groundbreaking evidence on the improvement MenQuadfi brings to the meningitis field, reinforcing its best-in-class profile. You certainly remember data we provided in December 2021, showing that MenQuadfi induces a superior immune response against MenC compared to competitors' products. Since that time, we have generated additional impactful data demonstrating, yet again, MenQuadfi's best-in-class profile. On the left part of the slide, you can see the immune response induced by MenQuadfi versus Pfizer quadrivalent vaccines in adolescent population.
This graph is pretty self-explanatory and shows the improved performance of MenQuadfi across all four ACWY components, and particularly for serogroup C, which is fully consistent with what we showed last time. The graph on the right shows the immune response induced by MenQuadfi, this time with GSK's quadrivalent vaccine in infants and toddlers. Here, it shows that 3 doses of MenQuadfi induce similar, if not a better immune response, than four doses of GSK vaccine. These are obviously important for MenQuadfi, but on top, as you can imagine, they also give us a lot of confidence when using MenQuadfi as our backbone to develop a best-in-class pentavalent MenACWY vaccine. Let me tell you something that's really exciting. Next year, in 2024, MenQuadfi will be the only product available in the presentation preferred by 80% of HCPs, ready to use prefilled syringe, which is so much more practical.
Due to the use of silicone in prefilled syringes, no manufacturer had succeeded to achieve this to date. After considerable process development and through the right exclusive collaboration, we resolved this CMC challenge. As you realize, this is another major improvement for our customers, enabling seamless administration. We have high confidence that this new feature will become a significant differentiator, as we observed with several other syringe products in multiple markets. To say the least, meningitis immunization schemes are quite complex and highly heterogeneous, which means that you absolutely need the most complete profile to be able to play and win globally in this market. With its most complete product profile, MenQuadfi is best positioned to address current and future immunization schedules for meningitis vaccines. As an illustration here, age groups. As you can see on the left part of the slide, recommendations vary greatly between countries.
Here again, MenQuadfi broad indication is a key advantage to sustain growth over the coming years. Now, the elephant in the room, it's a small room. Some believe that the pentavalent is going to take over and the quadrivalent is going to be replaced. In reality, that transition will not be immediate at all. In fact, a quadrivalent vaccine will be relevant in the market still for quite some time. Why is that? Well, I think the pentavalent will not be effortless for health authorities and will depend on multiple factors. Immunization schedule compatibility is one, epidemiological trends by age and serotype is another one, and last but not least, cost effectiveness and impact on public budgets does matter. Let's illustrate this with the U.S. market.
As you know, ACIP gathered last week to discuss potential schedule evolution, and they confirmed it's not going to be a walk in the park for the pentavalent. It will take time and the right product profile, which, by the way, could be one of the reasons why GSK is planning to come with a second-generation pentavalent in a few years from now. Let me remind you here, the current schedule in the US, meningitis ACWY vaccine is given in routine, two2 doses at age 11, 16, and that's where MenQuadfi leads. meningitis B vaccine is optional, and it's given with the 1st dose at age 16, then a second one a few months later, with limited coverage rates because of the recommendation, shared clinical decision-making from ACIP due to the value perceived of this vaccination.
That means the first doses, the 11-year-old doses, is on the table for pentavalent, just to start with. The only change ACIP actually opened the door to last week is for the second dose at age 16 to be optionally combined with the first quad dose. However, still with the same optional scheme, which means that the schedule essentially remains the same, and under such recommendation, we know that the ramp-up of the pentavalent will only be slow. To sum it up, MenQuadfi, with its best-in-class profile, is poised for continued success. Now, as leader in meningitis vaccines, we continue to innovate, and we are building the future based on our best-in-class MenQuadfi backbone. Saranya, do you want to share with us the exciting set of data that we have and you brought for us today on our meningitis portfolio, please?
Thank you, Thomas. We've indeed made significant progress in our portfolio. Let me start with our meningitis B program and the data from our phase I/II trial in adults and adolescents. As a reminder, this vaccine candidate is based on multiple components selected to offer broad protection against circulating strains of meningitis B. We tested different formulations in order to find the sweet spot between reactogenicity and immunogenicity, and we compared them to two licensed vaccines, Bexsero and Trumenba. Today, I'll share with you the data from the adolescent cohort, and we are very pleased with the outcome. What you can see here are the data from two formulations that we intend to progress to the next trial. The data presented here are the functional serum bactericidal responses against different MenB strains.
The left part includes the strains that we use to design our vaccine, and the right part refers to strains not in our vaccine. The color code informs you of the immune response rate observed with our vaccine compared to Bexsero and Trumenba. The green cell indicates the strains for which we observed the seroresponse rate at least 15x higher than the competitive vaccine. The dashed green cells represent the strains where we saw a similar immune response to the competition, meaning within - 15 to + 15% seroresponse rate range. The yellow cells represent the strains against which we had a lower response than the competition, noting that this includes the strains that were used by our competitor to develop their own vaccine. What did we observe? First, very pleased that our vaccine candidate was well tolerated, in line with competitor's vaccine in this population.
Second, all components of the vaccine were immunogenic, induced a functional bactericidal immune response. Finally, the breadth of the immune response that we observed and the coverage of the different strains were completely aligned with our prediction. This data gives us the confidence to proceed to the next stage. Our next stage includes progressing our MenB vaccine to toddlers and infants, but it also includes the development of a MenPenta vaccine, building on our best-in-class MenQuadfi vaccine. The preparation of our phase I/II trial for our MenPenta is underway, and we have significant reasons to believe that this vaccine will perform well. Let me share some preclinical data that will give you the same confidence. On the left side of this slide, you see the stability of the different components when mixed in our pentavalent formulation.
The upper graph shows the amount of free polysaccharide across all four ACWY conjugates, which doesn't increase over time. On the bottom part, you can see that the MenB components also remain very stable over time. On the right side of this graph, you can see that the different components did not interfere with each other in a rabbit preclinical model. This data green lights our advance of this program to a phase I/II study planned to start in the second half of this year. Overall, we are in a very strong position with our meningitis portfolio. We're setting new standards with our best-in-class MenACWY, the vaccine MenQuadfi. Our phase I/II readouts with our novel MenB formulation demonstrates strong potential for cross-protection across B strains and a very competitive product profile, thanks to its specific design.
We will be able to put these together to achieve our goal of a best-in-class, fully liquid pentavalent vaccine. Again, we expect this to be available in ready-to-use syringes, a real differentiator in this market, and we expect to file for registration in 2027. With that, let me hand over to Jean-François and Frank to walk you through the progress with our very exciting mRNA platform. Jean-François?
Yeah, we'll need traffic light in this room at some point. Thanks very much, Saranya. Thank you for walking us through this exciting data, also thank you very much for all the work that you and your team are doing on a daily basis. Really much appreciated. Now, for this session, I'm delighted to share the stage with you, Frank DeRosa, our mRNA Chief Technological Officer, and also the Head of our Biomarker and Research Group in the mRNA Center of Excellence. Together with Frank, we will give you an overview of the great progress that we have made with mRNA since we last talked in December 2021. I trust that by now, the RSV and the flu data have convinced you that we already have a leading mRNA platform.
We'll now share our robust innovation pipeline that will lead us to the next generation of mRNA. To achieve this stage, we have doubled down both on execution on one side, but also on innovation. As we speak, and I already mentioned, we already have in our pocket, the result of seven trials based on mRNA candidates. We've also assessed the clinical performance of three LNP, and we'll have two more by the end of this year. The pace, the breadth, and the depth of our research would not be possible without our people. There, as well, we've exceeded our ambition with more than 600 top-notch mRNA experts dedicated to mRNA science and technology. Increasingly important into this world are the collaboration that we have forged across academia, with example, our expanded collaboration with Dan Anderson at MIT.
Across industry, with multiple innovative companies, for example, Baidu or Inceptive, but also with government, such as the vibrant partnership that we forge with the Queensland state in Australia. Innovation is happening everywhere in our mRNA Center of Excellence, I'm going to review with Frank, the elements covered on the right of this slide. Before going there, I'd like to emphasize the importance of the end-to-end approach that we are pursuing in our mRNA Center of Excellence, and the role played by artificial intelligence and machine learning. As we all know, it takes an aligned and committed organization to generate, but also to structure the massive data set supporting the development of predictive and generative modeling. As we know as well, the performance of mRNA depends on multiple parameters, and all of them need to be optimized.
That's why we've built an organization where data scientists are working very closely with experts in antigen design, mRNA science, LNP science, biomarker, and translational medicine. They develop proprietary models across the full spectrum, learning from CMC, learning from preclinical in vitro, preclinical in vivo, but also from transnational trials. It's actually these iterative loops that propel us with high confidence toward next gen. I'd like to also highlight the expansion of our mRNA technology to bacterial targets. We all know that mRNA is particularly suited to express viral antigens, our data here on the left confirm that again. The charts on the right illustrate how mRNA vaccine candidate against acne and chlamydia can induce equivalent or even superior level of functional antibody levels compared to the recombinant protein equivalent antigen.
I'll leave it up to Sally to cover that a little bit later when we go through the early pipeline. For now, Frank, time has come for you to go a little bit deeper in our mRNA science. Frank?
Thank you very much, Jean-François, and good morning, and good afternoon, everybody. As we just saw, the versatility of our mRNA platform is an essential pillar to our ambition to create first-in-class and best-in-class vaccines and therapeutics. Although we're focusing on vaccines today, we understand the power of this technology and believe in the use of mRNA beyond vaccines, and we're currently exploring this further in other therapeutic areas in close collaboration with our pharma colleagues within the company. Vaccines are not perfect. As you've heard today, they require additional innovation. I want to begin with some key topics that you've heard today regarding areas of intense focus for us in research as we push into our next generation platform. Potency, reactogenicity, thermostability. You've heard this several times today. You see it on the screen. These are recurring themes that are critical to an mRNA vaccine success.
Solving these will certainly open the doors dramatically for broader applications that are mentioned here today. I'd like to begin with potency and how we are approaching this parameter. There's many ways to approach this. You can look at the mRNA side of the puzzle, you can look at the LNP side of the puzzle. For mRNA, think about how you can do this to increase the potency. You can increase it through antigen expression. You can increase this through increasing the stability or increasing the purity or the quality of the mRNA. Shown here is an example of how we are doing early efforts here to improve the amount of antigen produced per molecule of mRNA. That's what you're seeing on the right here, to improve the instructions that we want to deliver to our bodies.
This is through sequence-specific changes, where we computationally design hundreds of thousands of these sequences, narrow it down to multi-hundred, synthesize them, and test them. We can see just by optimizing the sequence in this way, we can see a significant increase in the amount of antigen produced per given mRNA molecule. When we dive a little deeper, we can attribute this increase to an increase in translational efficiency. This is what's shown in the center here of the slide. What's known as ribosomal engagement. That's the machinery in our cells that recognizes the mRNA, recognizes those instructions, and can read them easier, and that's what's affording more antigen per mRNA delivered. When we go one step further, we can visualize this increase in antigen expression through cell imaging. That's what's shown on the right there.
Much more orange fluorescence results in much more antigen produced at a given dose. I mentioned we can approach potency through the mRNA side of things. This is just one example. It can also be approached through the delivery system, and in our case, we're talking about lipid nanoparticles or LNPs. I just wanna give a little refresher here to briefly reintroduce LNPs and what they're typically made of. Now, typically, they're made of four components, what are listed here. I would say the vast majority of focus in the field is on one component, on that first guy up there, the ionizable lipid. No doubt, we are focused there as well, and there's a good reason for that. It can drive the potency, it can drive cell distribution, it can drive the tolerability.
We've made extensive progress creating a vast and differentiated chemical space around these lipid families. What you're seeing here in the upper left-hand corner are multiple different lipid families, chemically defined, chemically unique from one another, that are showing superior potency over benchmark lipids there. We're not stopping at that one component. We're innovating around the second component as well, where we've designed novel, proprietary helper lipids here, a space largely unexplored in the field. We've looked at the third component as well, where we've identified novel sterile derivatives. When we add these to our already potent ionizable lipids, we begin to see double, triple, even quadruple the amount of protein produced at the same dose, really boosting that potency.
Again, we continue to innovate, and we move to that fourth and final component there, where we're swapping out that PEG-lipid for alternative lipids there that maintain that activity and could have beneficial properties there. We're not just looking at one component, we're optimizing around the entire LNP, all four components. Actually, we've pushed further than that because we've identified and developed novel proprietary excipients that can act as a fifth component here, and we're seeing some really nice activity from some of these. Again, up to four times the amount of protein when we just add this fifth component into our delivery systems. Why is this so important? Higher potency can provide a potentially lower efficacious dose and better tolerability. That leads us to our second key focus here, which is reactogenicity.
We're taking a comprehensive approach to building our understanding of what causes the reactogenicity that we observe with these vaccines. We're doing this by generating clinical data across a large number of platform variables. Now, you may recall the graphic that Jean-François just showed, that cycle of preclinical to clinical, in vitro to in vivo to human, and how these data relate to one another and how we can feed that back into the platform. This is the clinical piece of that cycle. This is where we're interrogating platform features clinically to allow us to build a predictive model that will hopefully allow us to increase our speed for candidate selection and also our probability for success. That's the goal. Some of those platform variables include the type of mRNA. They include different disease targets.
They include single versus multivalent approaches, as well as a variety of different LNPs. All of these studies, including ongoing ones, help us to rank these different vaccines, these different variables. We can show this in a plot shown here, a very simple high-level plot, where we can plot immunogenic versus reactogenic performance here. Very cool stuff. It allows us to visualize that quite easily, how they're performing. I just want to go a little bit deeper here. I want to share with you a snapshot of the approaches that we're taking to help link our preclinical observations with our clinical ones. We're utilizing a proprietary MIMIC system. This is an ex vivo system, looking at immune cells and how they respond to any external variable we want to test.
The figure on the left is detailing cytokine responses following an in vitro vaccination of this MIMIC system with various LNPs. The improvements that we're seeing in the reduction of inflammatory cytokines can clearly be observed when we move from one mRNA to the next LNP iteration that we've selected for clinical development over time. These reductions that we see preclinically in the MIMIC system can be similarly observed clinically as we progress on the right side of the slide here, where we see a marked decline in the frequency as well as the severity of adverse events as we move from unmodified to modified. This is the type of mRNA. Other variables include different LNPs, as I mentioned before, and we've explored that in the clinic as well, and what we're seeing here is a comparison of two different LNPs.
First, I would note the low % of grade three across the board in these two first-generation formulations, with LNP showing clear differences from LNP- 2, LNP- 3 to LNP- 2 there, with a number of different readouts. This is a trend that we observe in our MIMIC system preclinically as well, and we're taking this even further. We've started to identify key cytokines and genetic signatures that we're trying to correlate and link to adverse events that we see, and assign pathways associated with that, for what we're seeing preclinically to what we're seeing clinically in humans again. We're very excited about this progress. We're continuing to build rapidly to develop this further. All right, I've touched upon two of those topics, potency and reactogenicity.
That third one that we've talked about, and you've heard a little bit about, thermal stability, and it is a tough nut to crack, no doubt. You heard from Bill earlier, the need for this in established markets such as flu or a minimum of nine months stability, preferably 12 months plus, as a liquid under refrigerated conditions. I'd like to begin here just to explain how we see the pathway for success, as there are multiple challenges associated with this and many factors involved. The LNP plays a role, mRNA plays a role, scale plays a role, and handling across the entire industrial chain plays a big role in this. If you think about what we mean when we say thermal stability, it's about your product being stable at a given temperature over a given period of time.
It's not just about the LNP, but it's the mRNA inside of it. That's actually the real challenge there. When a product is scaled up to large scale, early clinical phase, late clinical phase, commercial stage, when you have to perform fill-finish, when you have to pack and ship, all of these processes chip away at your integrity because they involve either refrigerated conditions or even ambient or room temperature conditions sometimes. A lot of work has gone into understanding what drives this and how we can prevent it. I first want to begin by saying it is possible, it is possible to have an mRNA LNP stable for 12 months as a liquid under refrigerated conditions.
I want to point out here, this is a prototype LNP with specific features that are resulting in this, and we've learned a lot through this prototype, as well as through additional endeavors on factors that can have a beneficial effect. The key is, how can you incorporate this knowledge into your leading product? We've made significant gains there. Here in this example, we've shown up to nine months relative stability with our QIV LNP candidate. This is a flu candidate. This is a quadrivalent flu candidate in particular. Progress is certainly being made, and we continue to drive, we continue to improve, we continue to learn and develop our expertise in this. As we move into the last slide here, I'm very excited at the progress we've made on so many fronts.
We have firmly established a competitive platform. It's been an incredibly productive 18 months since we last spoke. We're addressing all of those critical areas that we feel are required for success through technological advancement, as well as biological innovation through antigen design. All of that together is putting us in a strong position to cross new frontiers. To expand on these new frontiers, I'd like to welcome Sally Mossman to the stage, our Head of Research Portfolio Strategy. Sally?
Thank you so much, Frank.
Hi, everyone. It's delightful to be here. For this next section in our event, I have the great pleasure to spend some time talking with you about the earlier programs in our pipeline. These are both programs that I'm particularly excited about. In each case, we're working to address as yet significant unmet medical needs and pushing the frontiers of science and vaccinology. First, today, we're going to be updating you on our chlamydia vaccine program. We'll be joined by Dr. William Geisler, who is going to share his significant expertise in the chlamydia field by educating us on the burden of disease there. This will be followed by a view on the data that has enabled selecting our final vaccine candidate to progress the clinical evaluation.
Secondly, we're going to cover our highly innovative therapeutic acne vaccine program. We'll be sharing our encouraging preclinical data, which has allowed us to embark on preparations towards a clinical study start later this year. Without further ado, let's move on to chlamydia. It's my absolute pleasure to welcome Dr. William Geisler to the stage. Dr. Geisler is a Professor of Medicine and Epidemiology in the Division of Infectious Diseases at the University of Alabama at Birmingham. His expertise is in adult infectious disease, particularly sexually transmitted infections. And in this capacity, he has served as an expert consultant for the CDC and the WHO. With that, Dr. Geisler, the floor is yours.
Okay, thank you for the introduction, Sally, welcome everyone to this presentation. I'll be discussing the continued high burden of chlamydia as a justification for why we need a chlamydia vaccine. If you've not heard of chlamydia before, it is a sexually transmitted infection. It is due to a bacteria called Chlamydia trachomatis. This is a bacteria that infects humans, actually inside human cells. That picture on the right is a fluorescent image showing you chlamydial bodies in the red, infecting a host cell, which is shown in green there. Okay, the World Health Organization monitors four curable STIs. One of those four is chlamydia. The other ones are gonorrhea, syphilis, and trichomonas. This global map here shows you how common these four curable STIs are worldwide.
If you start to break down the actual numbers and you look at chlamydia, within the bacteria, there are about 129 million new cases of chlamydia each year, which is more than gonorrhea and syphilis, the other two bacteria, put together. Chlamydia is the most common bacterial STI worldwide. Why is it so common? Well, it's common because it's a chronic infection, and most people who have this infection actually don't know that they have it. If you look at some of the earlier studies, they show that of women that have chlamydia, over 75% have no signs or symptoms of infection, and for men, that's over 50%.
Some of the more recent studies us, using some of the newer molecular technologies, show that actually the asymptomatic rate probably exceeds 80% in both men and women. Now, once you get infected with chlamydia, it lasts for at least weeks to months in pretty much most individuals. There have been two studies in women that show that at least 50% of women are infected for one year or longer when they have chlamydia. On the figure on your right there is one of those two studies. This started as a natural history HPV study. As part of that study, they collected specimens about every six months, and then later on, went back and tested all these specimens for chlamydia.
What they found is that if you look at women at the beginning of the study who had asymptomatic chlamydia, and as if you follow the figure to the right and you, and you look at one year, about 50% still have chlamydia if they're not treated about one year later. If you go out to about three years, there's still about 5% with persisting chlamydia even during that time. Despite the asymptomatic nature of chlamydia, don't let that fool you. Even in its asymptomatic state, it causes significant health consequences, particularly in women. In women, when this infection gets into their genital tract, it can spread to their upper genital tract, something we call pelvic inflammatory disease, or PID for short, and that occurs in about 10%-15% of women who have chlamydia.
Once you have PID, about one in every five women or so can get infertility. About one in three women can get chronic pelvic pain lasting weeks to months. Then there's about a 3-fold increase risk for women who have PID to get something called ectopic pregnancy. That is a non-viable pregnancy, where basically the fertilized ovum implants in the wrong place, and that can lead to hemorrhaging and other complications in women. Men do get chlamydia, of course. Men can have symptoms from chlamydia, they can have decreased fertility, but one of the greatest burden of chlamydia in men is simply that men transmit it to women, and then women get the reproductive morbidity that we just talked about.
Women who are pregnant and get chlamydia, they can lose the baby during pregnancy, they can lose the baby right before birth, they can have a premature delivery, and that baby can be low birth weight and have other complications because of its low birth weight. When a mother has a vaginal birth and that baby passes through the birth canal, if the mother has chlamydia, the baby can get an infection in its eyes or in its respiratory tract from the mother when that happens. The other thing that many people forget about, but it's very important, is that when you have chlamydia, it recruits inflammatory cells to your genital tract, such as CD4 T cells. CD4 T cells are the target cells for HIV. You have an increased risk to get HIV if you are chlamydia infected.
I've just told you that chlamydia is very common and has these important health consequences. Of course, there are control programs in place to try to prevent chlamydia. Pretty much most higher resource settings, as well as many lower resource settings, have these control programs in place. They're quite comprehensive. You can see here there are chlamydia prevention measures, including recommending abstinence, which, as you can imagine, that doesn't work so well. you know, promoting sexual health education, promoting use of barrier methods like condoms. What we don't have is a vaccine for chlamydia prevention, the ultimate form of prevention. We do, of course, try to identify people that have chlamydia.
We, you know, we certainly test them, and what's recommended for asymptomatic young women, men who have sex with men, and higher-risk individuals, is that you get tested for chlamydia using very sensitive molecular tests once a year. If you have signs or symptoms suggesting chlamydia, that you get tested with these same types of tests. If we find chlamydia in you, we have very good treatments for the patient and for the partner, either a seven-day antibiotic course, an antibiotic called doxycycline, or a single-dose treatment. Right there, while the patient's sitting in front of you, give them a single-dose treatment of azithromycin. These two antibiotics cure over 95% of genital infections with chlamydia. We have no antibiotic resistance concerns with these antibiotics, despite using them for over 40 years. You would think, gosh, right, these control programs sound great.
We've got these prevention measures. We've got really, you know, really accurate tests. We have very good treatments. We can control chlamydia in the world, right? Wrong. Okay? Our chlamydia control programs, pretty much everywhere in the world, have been ineffective in controlling chlamydia rates. This CDC surveillance data shown here on the left, I think, illustrates this quite nicely. CDC has been tracking chlamydia since 1984. It became a notifiable condition in 1995, the most reported infection, actually, in the U.S. prior to COVID. You can see the rates have gone up essentially every year, except for perhaps 2020, but that was a false decline at that time because the highest-risk people were not getting the testing done during COVID. It looked like the rates were going down, but they weren't going down, they were going up.
If you wanna look at specific numbers, in the U.S., over 1.6 million cases of chlamydia get reported to CDC because it's required to report to CDC. Those are the ones we actually know about. Research suggests there's actually about 4 million cases, new cases, each year of chlamydia in the U.S. alone. Okay, you're probably going, "Well, why aren't these control programs actually working?" Well, earlier, I kinda mentioned that basically, most chlamydia is asymptomatic and it's chronic. Many chlamydia cases go undetected and untreated. We simply don't know about them. Either patients don't go to get testing done, or they go see doctors, and doctors don't do the testing. It just doesn't happen. Very important to this discussion that you've been hearing today is something regarding immunity to chlamydia.
It turns out that most individuals, when they have chlamydia, they do not develop good, long-lasting protective immunity to natural infection with the whole bacteria itself. Basically, if they develop any immunity, it's pretty short-lived, within a matter of just a few months, and then they just get reinfected over and over again. About 20% of people are reinfected again within about a one-year period after they are infected. What's really kinda crazy is that we had these control programs, right? Our goal is to decrease chlamydia and the complications, but what animal models show, and some limited human studies, is actually that the more aggressive we get in trying to find chlamydia and treat it, and treat it earlier in the course of infection, we're actually taking away one's ability to mount a protective immune response.
They actually become more vulnerable to chlamydia than if you didn't treat it at all, and then they just get reinfected over and over and over, okay? That's just to kind of summarize the points I've been making here, is that chlamydia, again, the most prevalent bacterial STI worldwide. Infections are chronic, infections are mostly asymptomatic. We have these great control programs in place. They do a lot of different things, but what they don't do is actually decrease chlamydia itself, okay? Really, there's nothing else out there from a prevention perspective right now that's going to decrease chlamydia, except for a vaccine. That's really the strong justification for why we need a chlamydia vaccine. Thank you.
Thank you so much, Dr. Geisler. We really appreciate that. We welcome you back on stage for the Q&A afterwards. I'm sure there's many questions and interest on chlamydia. We heard from Dr. Geisler about the burden of disease and the impact on patients, but then I wanted to supplement that by sharing this slide with you, as I find it really quite striking. These are CDC data from a study highlighting the significant direct costs associated with sexually transmitted infections in the U.S.. As you can see from the graphic, that a significant portion of those is actually attributed to chlamydia. It's lower only than HIV and HPV, in fact.
The Queensland government in Australia is well aware of this burden, and this is why they have elected to support our chlamydia vaccine development program through our Translational Science Hub in Queensland. Let's take a look at the science behind chlamydia and what we know about protective immunity. Chlamydia is a complex pathogen, as you can see from the left-hand side of this slide. It's actually unusual in that it's a bacterium, but as Dr. Geisler told us, it spends part of its life cycle inside human cells. In fact, it's almost like a virus in that regard. It has two different stages in the life cycle: the intracellular reticulate body and the extracellular infectious particle, which is the elementary body.
For the intracellular reticulate body, there is a wealth of evidence to support a role for CD4 T cells secreting interferon gamma in mediating protective immune responses. In addition, it's likely that antibodies that recognize the extracellular elementary bodies will also be important in infection. Putting this together, our targeted immune profile constitutes both antibodies and CD4 T cells. In addition, genital chlamydia disease is caused by a few different serovars or serotypes, if you will. It's therefore important to design our vaccine and to demonstrate broad recognition across the relevant serovars. Finally, we need to show that the T cell-inducing properties of the vaccine have broad population coverage in terms of HLA recognition. Our preclinical data show that through our innovative multivalent antigen design, we are indeed meeting this targeted immune profile. Let's be clear, we did not achieve this overnight.
In fact, we had to screen 99 different antigen designs and 100 different mRNA constructs to come up with this final vaccine composition. The graph on the left shows that with our antigen A design, we are able to induce CD4 T cells secreting interferon gamma that recognize broadly across relevant serovars. The remaining data illustrate that antigens B, C, and D each induce cross-reactive antibodies capable of binding native elementary bodies of diverse serovars, further enhancing our vaccine candidate composition. I'm delighted to announce that we are progressing this vaccine into the clinic for a phase I/II in 2024. Let's move on to acne now. Acne is a chronic inflammatory skin disease, and I'm sure everyone is very familiar with acne as a disease.
In fact, I'm sure almost all of you know someone who has suffered from this. In fact, acne is the eighth most common chronic disease globally, and it's increasing. The chronic nature of acne disease really places a heavy burden on sufferers, and it can cause major psychosocial impact. The long-term use of antibiotics in treatment regimens is not ideal, and it's likely contributing to increased global antimicrobial resistance. Yes, acne medicines do exist, but they're not checking all the boxes for patients. On top of this, they bring significant economic costs. Recent market research that we conducted highlights the treatment gaps that I just referred to, signaling the need really for better solutions across all dimensions, reliable long-term efficacy, ease of implementation, and lack of serious side effects. That's really key. The quotes on the left side of this slide really highlight that gap.
We heard from a dermatologist in Germany, "Isotretinoin has the efficacy, but it's complicated and has risks. None of the options we have give us everything we need in one treatment." A dermatologist from the U.S. told us, "Acne is very hard on patients because it's a disease everyone can see. I don't take it lightly because I know it can have psychological and social ramifications." Those powerful messages speak for themselves, I believe. Our approach in the acne immunotherapeutic space is an ambitious one. The targeted approach is designed to restore a healthy microbiome balance. Our strategy leverages the antigens we acquired through the Origimm deal. The graph on the right illustrates how the proof of mechanism for those Origimm antigens has been validated by the generation of robust antimicrobial antibodies with antigens delivered in the form of proteins, in this case.
In addition to the Origimm antigens, we've further combined with one that we developed internally. We've honed what are generally very challenging antibacterial functional assays, we're leveraging this critical know-how to move at full speed with our vaccine candidate. Importantly, due to the inflammatory nature of this chronic disease, we clearly benefit from Sanofi's significant expertise and prowess in the field of immunology and inflammation across the company. The disease acne vulgaris is a result of dysbiosis of the skin microbiome, and it's driven by the outgrowth of pathogenic Cutibacterium acnes strains. The vaccine is therefore specifically targeting this bacterium and its mediators. Our mRNA vaccine candidate is designed for therapeutic use in patients, and it addresses multiple mechanisms of action to enhance the probability to succeed. Let me walk you through those mechanisms now.
The Origimm antigens are overexpressed on the surface of pathogenic bacterial strains and therefore are included in the vaccine to induce antibodies capable of killing those strains. In addition to that, there's the additional potential functionality to block essential bacterial mechanisms such as iron uptake and cellular adhesion. The final antigen in the vaccine is designed to block inflammatory mediators to interrupt the cascade of inflammation that is so characteristic of acne disease. Our preclinical data on the mRNA vaccine candidate have shown proof of concept for the vaccine design and allowed us to engage in the GMP production and readiness for phase I/II. Let's walk through the data. On the left side of the slide, mRNA constructs expressing the Origimm antigens 1 and 2, are able to induce antibodies capable of killing C. acnes bacteria....
to a degree, at least equivalent to what we've seen with recombinant proteins. Reiterating the point that we heard from Jean-François earlier. The antigen 3 construct induces antibodies that successfully neutralize C. acnes inflammatory factor, and again, it's to an equivalent or even superior in this case, for mRNA compared to recombinant protein. Furthermore, when we add the 3 antigens together as mRNAs, we see no interference in overall functional response, and these data are shown on the right side panel of this slide. Collectively, these data support moving ahead with this multivalent mRNA vaccine candidate, and we initiate our phase I/II in the patient population already in 2023. And I have to say, we eagerly await the data from that trial. Let me just end by saying that we are incredibly excited by our early pipeline.
I really look forward to being able to disclose more with you at a future date. We're moving rapidly into new areas. We're supremely focused on addressing so far unmet medical needs, and importantly, being open to leverage the right technological solution to meet the challenge, be it mRNA, being it recombinant protein, being it monoclonal antibodies, or beyond. Science leads the way. As we move into fields of therapeutic vaccines, the association of infectious agents with chronic diseases and interventions to address microbiome imbalance, we're strongly enabled by our state-of-the-art immunology and our world-class antigen design. I thank you for your attention today, and with that, I'm going to hand the floor back to Thomas, who is going to close out our session today. Thomas, the floor is yours.
Thank you. Thank you very much, Dr. Geisler. Thank you very much, Sally. Great science progress. It's been fantastic to share with all of you our strategy, our capabilities, and our vaccine industry-leading pipeline. Before we move to Q&A, sorry, allow me a few words of conclusion, giving a lot of time for Q&A, I understand. To summarize the data you've seen today. As shared through the presentation, we strive to deliver a pipeline of best-in-class or first-in-class vaccine to improve people's lives. We intend to do so at pace, like we've done over the past 18 months. Since we last met in December 2021, we received three significant new product approvals, the latest being Beyfortus, which addresses a major unmet medical need. We are building a leading-edge mRNA platform. Our teams are exploring new ways to further improve that technology.
We are moving at speed with six new vaccine candidates, having entered or will enter phase I new trial over 2022 and 2023. As mentioned before, we intend to bring at least, that's the important part, at least five first-in-class, best-in-class vaccine candidates into phase III by 2025. To conclude, we confirm that our ambition is to deliver annual sales exceeding EUR 10 billion by the end of the decade. That is well within our reach. To get there, our major strongholds will remain in differentiated flu vaccines, complex pediatric combinations, and meningitis immunizations. They will remain key parts of our growth journey. On top of this strong foundation for our business, our R&D transformation and acceleration is now enabling us to add key new franchises.
A best-in-class RSV franchise, starting by the launch of Beyfortus in 2023 and covering all the unmet needs in terms of RSV protection. A very competitive PCV21 to enter a multi-billion pneumococcal market with our partner as a first product into this core pediatric segment. Finally, new mRNA vaccine, such as chlamydia or acne, that you've just seen. Those are not just me too or me better. We expect them to be truly transformative products, first-in-class immunizations. That's pretty simple. We're building exciting assets, we have the team, and we have the fundamentals. We're now 100% focused on the execution. With this, let's now turn on to our second Q&A.
Okay. Thank you. Yes, maybe we can squeeze you all on stage. We're now going to get to our second round of questions. I will probably try and first go to those that didn't have a chance in the first round. If I could maybe start the same, if possible, no more than two questions, please.
Perfect. Zane Abraham, JP Morgan. Thank you for taking my questions. Two for me, please. My first is just on PCV21. The phase II data that you showed, again, on dose three, showed strong response data versus registration hurdle on I think every strain, except for maybe strain 6B. Just wanted to understand how important that strain is for overall efficacy, you think, against invasive pneumococcal disease? Maybe a bigger picture, how important do you think more functional endpoints in terms of efficacy against IPD or hospitalizations would be needed for your PCV programs to drive approval, but also uptake, ultimately? My second question, if I may just going back to the first session, it's very clear that Fluzone High-Dose is the bar.
Just wondering if you could provide us with an update on your expectations for Fluzone High-Dose up this year?
Thank you.
While the team is preparing the answer on PCV21, I can take the first question quite easily. We really focus even today on the pipeline, on R&D. We have the pleasure and the chance to have quarterly earnings every quarter, so I'm sure we'll talk about that very soon, probably in one month from now. We're in the pre-booking season, and what we discussed before at the last quarterly earnings is still there, but we'll have more discussions in 1 month from now. PCV21, I'm turning to you, and if you want to comment with them.
Yeah. Indeed, this might be a weakest point in our PCV21. We believe it's very much manageable. Actually, we've simulated what would be the outcome of phase III if we were to run it based on the phase II data, and very confident that it will pass the bar. Let's be clear about that. Yes, every serotype might be important. If it's not important today, it might be important tomorrow because you know, the serotype evolution in PCV is important. That's why the 9N is extremely important.
Finally, also, just to clarify that for you in terms of regulatory acceptance, clearly, the regulators look at the totality of the data, and for example, in the Pfizer pediatric trial, they missed on six serotypes, and still, looking at the totality of the data, got the approval and recommendation for this vaccine. That's, what I would say at this stage.
Maybe in terms of uptake, we don't see any potential recommendation in the PCV pediatric market. It's going to be about the intrinsic of the product. We know we're going to come with a competitive product, which is going to make a difference for providers. We have the portfolio, we have the connection in the U.S., in the different countries, the contracting play, to foray into this market and have a ramp up when we get approved. Let's deliver this product profile, and we're convinced that it's a, it's a hard profile that will help us make a difference.
If we have the gentleman in front of I.
Hi, Evan Wang from Guggenheim. I have two questions on PCV. With respect, have you shared updates or can you provide an update on the adult phase II data? Will you have a direct comparisons to PCV20, or do you plan that in peds and adults? Second, on the next gen approaches in PCV, the data on the non-CRM were interesting. Can you talk about how you're thinking about using that to expand on additional serotypes and how far you think you can go with the non-CRM carrier beyond 21? Thanks.
I think we may link that question to the question that we had from David before.
Yeah.
Definitely. Pneumo Adult, you want to start?
Yeah, so for sure, for the Pneumo Adult, as you have seen, today, we are sharing quite a few data, so we needed to be selective on what we share. As you heard, we are also very conscious about where we allocate our capital, and we are looking for first-in-class, best-in-class vaccine. When we look at the competitive environment in the older adult space, but also when we look at the epidemiology and some of the avenues that our competitor are taking, we're thinking maybe it's not a good idea to allocate capital to the older adult at this stage. Yes, we are considering potentially two different options. As you see, there are two options in the field, either going for a vaccine that is specifically designed for the older adult or adding more serotypes.
I can take the question on how many serotypes we can put on the new carriers. Actually, I will take the question by not taking it, because obviously, the field is very competitive. We know that others are also considering using other carriers when we are doing it. Actually, we are not going to share that information at this stage.
Very glad that you understood that the new carrier is also very important.
If we go to Richard.
Richard Parkes from BNP Paribas Exane. Couple of questions around the same topic, really, on the technology platforms and mRNA. I think you mentioned nine different technology platforms within vaccines, but the two truly sort of novel new vaccines, chlamydia and acne, are both based on the mRNA technology. Could you talk about the reasons for going with that platform for those two vaccines? Is it based on being able to do something that you can't do with other technologies, or is it that you can just move more quickly in assessing new antigens and combinations, et cetera? The related question is just related to that. Now, you've had mRNA in-house for some time. How do you feel that's going to impact R&D productivity within vaccines and the benefits there longer term?
I think it will be great on R&D productivity because, of course, we can go faster to clinical into multiple spaces, and especially once you have your library of LNPs, you build all the preclinical data, and that gives you an ability to go very fast into phase I/II , and move on. To the first question, and I'm transferring the mic to you in a second on this. On the first question, how do we select the platform? It needs to be what's the best platform for the target profile. On the two examples you've seen on chlamydia and on acne, we're looking at different technologies, and then we're selecting based on what we see in the early stage of research.
You've seen that we are able to express more antigens with the mRNA platform than with the protein platform. Both of them are immunogenic, both of them express the proteins of interest. It's really about making sure that when you look at the evolity, evolutility, evolitivity, the ability to evolve the platform, sometimes you have to go back to normal words.
As well as the trade-off between ability to generate the right amount of antigen and the reactivity profile, then we find the sweet spot.
Broader, broadest toolbox across the vaccine industry. Important to note, nothing is missing. We have everything we need to deliver the vaccine we need. That's one important piece. As Sally was saying, science is leading us and data are leading us. I also want to add here, you could see how we use the different platforms across the portfolio. We have made substantial progress on expression of bacterial antigen with mRNA.
We don't say that all the bacterial protein can be expressed in mRNA. That's why, again, generating the right piece of data, having the right antigen design team, having the right immunology is going to help us narrow down and select the platform we want to have. Sally?
Yeah, just a quick point to add on to that. For chlamydia in particular, there's one of the major antigens that most people use in their vaccine is a highly complex molecule. It has multiple transmembrane spanning regions, we believe that mRNA is actually uniquely suited to presenting that antigen with appropriate native conformation. The other thing I think is in both cases, we're looking at multivalent vaccines, right? mRNA, of course, is particularly flexible and well suited to multivalent.
If we go to Joe.
Thank you. My questions go back to the first presentation. I think it was on slide 38, where it showed the amount of increase in antibodies you got with your RSV in older adults, and it was only about 5x . In Glaxo's, those older adults is a higher number than that. How competitive is that relevant? You know, is that in itself predictive of ultimately how successful a vaccine might be? How do you think that you're going to compare? Are you confident that the other two components that you're putting with it have got an equal sort of decay rate, such that you're going to get a vaccine that you're going to use every two or three years?
If one of the other components needed to be revaccinated every year, then it wouldn't work. I think we're all quite surprised at how the RSV one turned out. It's just your degree of confidence that the two other ones you've put it with are going to make a great every three-year vaccine, whatever it is. My second question is on machine learning. We heard about that a lot in 2021. We're hearing about it again. It enables you to choose the best possible antigens and get the best possible, you know, vaccine. Yet you have it, and the CDC doesn't have it.
If the CDC says, do A, B, C, and D, and your little generator says, Oh, I should actually be doing four other ones, do you go, "Well, we're going to be better," and then not be an approved vaccine? How do you actually get the world to benefit from this extra knowledge? How do you benefit from having this knowledge, which nobody else appears to have? Thank you.
I go to Sanjay for machine learning, and I do see machine learning coming into flu, especially with CDC, WHO. Is it added or is it instead? On RSV or the other, I come to you on the competitiveness and the data, where does it come from, what does it say, and what do we do for the phase IIb? Just one point before we go there. As we said, and it's very personal, as you can imagine. As we said on December 3rd, I don't think it will be every two years neither. It will be every three to five years. Saranya, flu first, we come back to you.
How you want?
You're way to respect rule of the bus. Go.
Thanks, Sean. I mean, I think it's a very valid question with machine learning flu. I mean, I think the concept we're trying to make sure we're talking about is the fact that there are companies who believe that you adding more strains might get you greater benefit. I think what we're basically trying to argue is that perhaps the selection of the strain is a better way to look at this. People have talked about selecting later, people have talked about time to manufacture. In essence, what we believe is I think the selection of the strain is probably the biggest choice you can make in demonstrating value in terms of efficacy. I think we are clearly in discussions with many different people, both academics, government, organizations, about how to move this forward.
I just want to take a step back and say we're very confident where we are with the machine learning approach. We need to demonstrate in the clinic that that approach demonstrates some clinical benefit, and we'll get there. Right? It's going to take some time, and that's where the confidence is going to come from for the CDC, for the WHO, to work with us in making that approach more feasible in the long term. I think there's some way to go, but we're getting there.
Yeah. Thank you, Saranya. Building on that, you understood there are two worlds. We can replace, but we can also add new strains selected by machine learning to create that difference. Still being compliant with CDC, WHO recommendation while offering the benefit that people are looking for. Back to the question on RSV or the adult. Of course, if we measure it's because we believe that it has some relevance. Is there a rate of protection? No, there is no rate of protection in RSV. We are very confident with the 5.4- fold increase we've seen in all the adult. Indeed, it's trending lower in the older adult compared to GSK and Pfizer. We explain it with two main reasons. The first one is really about the season.
You know, this year, after two years of COVID, we had an unprecedented heavy RSV season, meaning more people have been infected, more people have seen their antibody level boosted, and actually, when they are high, you cannot push them further. That's why the vaccine could not move everybody and reach that 5.4. I take an example. The company called Icosavax, that you may know or may not know. Last year, they reported with the vaccine a 6-fold increase. This year, they barely reach a 4-fold increase. Why? Because the season was particularly heavy. Another example, you know, J&J has discontinued its program, but they've published the efficacy data of the vaccine, season 2, season 3. The antibody doesn't persist season 2, season 3, and they still have efficacy. Do you need to reach a 9-fold increase?
We believe we might be there if we are in the right season. If we are not there, is it an issue? We believe we can protect with what we have. Honestly, we feel good about the data we have, and that's why we're moving forward with the phase I/II combo and with the phase IIb.
Couple of words about HMPV, PIV, we're going to be able to get three years of volume and how we need to look at?
Yeah, really interesting. Of course, we selected these viruses because they are the cousin, if I may speak like that, of the RSV. They are viruses of exactly the same family. They are viruses where the target antigen is the same, it's a fusion protein. We are very confident that what is valid for RSV will be transposable to what is happening for HMPV and PIV. It's totally different from the people who think flu and RSV were a virus that change every year, that change even within the season, compared to RSV, HMPV, PIV, that are very stable.
Joe, you're right. We need to see it in the clinic also.
Okay. I would like to try another one from the web. I know we have Steve Scala raised his hand. Steve, can you hear us?
Yes, I can hear you.
Yes.
Can you hear me?
Yes. All good.
Thank you so much. Two questions. Aren't potential COVID flu combinations a risk to your flu business? If not, why not? Secondly, at Sanofi's Vaccine Day in December 2021, the company projected the influenza market would grow to EUR 15 billion on 2030. Does Sanofi still believe that's a good estimate? Thank you very much.
I will go on the second one to our worldwide expert of flu, Mr. Pierre Verbeke, but because it's a question from the first one, you have time to come quite quietly. On the COVID-19 flu combo, great question. Not exactly the first time it's been asked. I think between 2021, and please go back to the transcript where we said COVID-19 flu combo could play a role, but if it happens, it's going to be very limited and going to take a lot of time to get there. I think since that time, how should I put it? flu vaccine development has been a humbling story for many companies because flu is not COVID, and flu is not RSV. We said the same statement about flu RSV. Why do I say that?
Right now, COVID-19 in 2021 was the high level of burden of disease. Fast-forward 18 months down the road. What's the burden of disease today? Not of 2021 and 2022, today, of COVID-19. What's the actual vaccination rate in the U.S. against COVID-19, and why is that? Is it because people don't care anymore about COVID-19? Is it because they are fatigued about the COVID-19 vaccination, or is it because it's not the right product profile, because it's still a first-generation mRNA? I think there's a lot of questions to answer on that now for 2023. There's also a lot of questions to think about: where is COVID-19 following that same trend going to be in 2025?
As we predicted in 2021, I reiterate that the flu burden of disease is going to be way higher than the COVID-19 burden of disease. Therefore, put yourself in the shoes of the U.S. ACIP recommending body. Are you going to say, "Oh, it's great to go for a combination vaccine for the 10% of the population that might still at that time maybe want a COVID-19 booster, if it's still recommended." To go for a combination, if it actually degrades negatively, the medical service provided on flu, i.e., the biggest burden of disease for the most fragile population on this planet, and you say, every year, I'm going to reduce their protection, and I'm going to increase the reactogenicity of the product, I don't think so. It will take a second generation of mRNA. Is it impossible?
That's why we're searching hard on it. We are still investing big into flu next steps, we are leading in flu now, we'll be leading in flu tomorrow. It's not the first generation, therefore, it's not in the coming years. Next generation, we're all at it. We are all starting on same ground. We have all reached the same level, if you wish, of average standard dose flu-like with higher reactogenicity on A strains in the first generation of mRNA. Thanks, no, thanks. It's not making it for the customer. Now it's on to the races for the next generation. We believe we have a very good chance.
Well, go to outlook.
I'll talk about the outlook. Is it okay?
Yeah.
I think our guidance is consistent with what we provided to you last 18 months ago, for a couple of reasons, actually, three. One, the elderly population continues to grow. Right, they're the most growing population in the next 10-year span. In that population, immunization rates still have a ways to go. In fact, some countries are less than half of where the WHO goal of immunization really is. There's a growing population, immunization rate, immunization opportunities still exist, and we're growing differentiated vaccines at a higher price point. The vast majority of these products, we believe, are going to be used in the elderly population at a higher price point. These three factors, plus, we see an incremental VCR of about a half a point a year, get you to the guidance that we provided you last time. Thank you.
Okay, we take one last question.
We take many more during the drink after.
Who should I pick? Well, Simon. Yeah.
Thank you. Simon Baker from Redburn. Couple of quick ones. Just on chlamydia, the emerging data looks very interesting. As you showed, the direct cost is less than $1 billion in the U.S. I'm just thinking how we should think about the price and target population for vaccination. A quick one on LNPs and the optimization you've been doing there. A lot of the focus on LNPs tends to be on temperature stability and protection of the mRNA itself, but there's been work done on the potential role of LNPs acting as adjuvants and also single component LNPs for tissue targeting. I just wonder if you could give us your thoughts on both of those as a potential in LNP research. Thanks.
For the LNPs, I'll go to Frank and Jean-François to complement Frank later on. You want to start on chlamydia, Thomas-
Yeah, sure.
Maybe Sally?
On chlamydia, I think you see the figure close to $700 million in direct costs, which is very close to the remaining cost of HPV, you see just next, and you see the business size in the U.S. of HPV billions. That's one part of the answer, and the other part is you add the indirect cost, the quality cost. You go easily to the $2 billion-$3 billion per year in the U.S. in terms of cost, and that's based on the data we have today, and we see the trends are going up, and the more we look, the more we find. Is it the next HPV? I'll let you think about it. We see a lot of parallel with that market and a lot of potential for public health, as well as in terms of economics with these vaccines.
LNPs. Go, Frank, go.
All right, sure. Great question on that. With LNPs, with adjuvanting, certainly familiar with the data that's been out there on that. Look, we're looking at a lot of different approaches for immune modulation up or down with various different entities, whether it be an LNP or whether it be another type of excipient for that. What you want to be careful, though, is the reactogenicity. We've already got an LNP there, you've got mRNA there, you see the reactogenicity already. Adding an empty LNP or exploiting the lipid from that regard, it's a fine balance, and we're very aware of that, and we're looking into it. With respect to targeting and using LNPs as targeting, there's two different ways to do this. I feel like you're referring to the types that are passive targeting.
Based on the lipid composition, it can go to different organs. We certainly have that capability, and we've generated a lot of data around that. There's also active targeting, where you can put an active targeting agent, which we're exploring as well, not just from a vaccine standpoint, but also from a therapeutic area standpoint also. We've got the expertise in-house. In fact, we've got that through a bunch of different technological platforms within Sanofi, so it's actually quite powerful. I think we're pretty unique in that regard. The technology capabilities that we have and the goal that we're doing and what we're exploring right now is synergizing those technologies within our company, which we think gives us much better advantage over other people out there.
Yeah, just to complement very quickly. Yes, we have all the technology we need in Sanofi. For example, we added Tidal via M&A in our portfolio about two years ago, exactly for that purpose, which is targeting of the LNP, not only to the organs, as some of are doing, but to the particular cells that you need to transform. Really, we have the toolbox we need to transform the course of medicine.
Um.
I just want to add a little bit more about the cost, which is in the billions of dollars each year. The cost for chlamydia is really driven by its complications, ectopic pregnancy, PID, and infertility. Infertility, in particular, is very expensive. Those costs continue to climb. Because ideally, what women are having done is something called assisted reproductive technology, but they have to go see a specialist for that. It's very expensive. Those costs continue to climb. What many people don't appreciate is there's a huge gap in the world. A lot of people can't access that infertility technology. We have a lot of people who need a vaccine because they're not going to have access to these complications once they happen.
Yes.
We're going to close the event now. We're already over time. A big thank you to my Sanofi colleagues from Vaccines. Special thanks to Dr. Geisler for all of you sharing your expertise, but also your passion. For those that still have time, you're very welcome to stay with us a little more, ask more questions. We're going to be back in the other room. Thank you very much and hope to see you soon at another R&D event. We're going to send out an invite shortly for an R&D day at the second half of the year.
The drinks room is fresh.