Sanofi (SAN) Earnings Call Transcript & Summary

Good afternoon, and good evening to Asia. I'm Eva Schaefer-Jansen of Sanofi Investor Relations. Welcome to this event. This is the fifth in a series of 5 R&D events, highlighting the accelerating pipeline momentum building within Sanofi R&D. Today, we will focus on the Phase IIb results of nirsevimab just published in the New England Journal of Medicine. As usual, you can find the slides to this call on the Investors page of our website at sanofi.com. Next slide, please. So I would like to remind you that information presented during this event contain 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 these factors. Next slide, please. So I would like to introduce you to our speakers today. We have here Thomas Triomphe, Global Head of Sanofi Pasteur; we have Su-Peing Ng, Global Head of Medical, Sanofi Pasteur; also Jon Heinrichs, Global Project Head, nirsevimab, from Sanofi Pasteur; and John Shiver, Senior Vice President, R&D, Sanofi Pasteur. Thomas will make some introductory remarks, and then Su-Peing will describe the major public health burden of RSV, after which, Jon Heinrichs will discuss the details of the Phase IIb results. John Shiver will then wrap up with concluding comment, including an update on the Phase III program. We will be joined then for a Q&A session that's going to close this call by some members of the executive committee. With that, I would like to advance to the next slide and hand over the floor to Thomas.

Better if I unmute. Thank you very much, Eva, and welcome, everyone. Thank you for participating. So speaking on behalf of my colleague here at Sanofi Pasteur, we are absolutely thrilled today with the publication of the detailed Phase IIb results that you have probably seen in the New England Journal of Medicine. This trial is the first of 3 pivotal studies for nirsevimab, a potent extended half-life monoclonal antibody for the prophylaxis of RSV infections in all infants, done in collaboration with AstraZeneca. As many of you know, RSV is a major disease, a major public health issue for all infants. And it is, to date, the leading case up hospitalizations in infant in the U.S., and in fact, in many countries around the road. Actually, in developing countries, in particular, RSV is the leading cause of infant mortality. So we do believe today marks an important development in the fight against this pathogen. And we do believe that nirsevimab may represent a truly transformational asset, one which offers a population-based solution for the very first time with a monoclonal antibody. Therefore, it is a parting shift in the prevention of this disease. You may now move on to the next slide. Thank you. First, I would like to remind you, on this slide, our Sanofi strength in vaccines. These are actually the same strengths that have brought us together with AstraZeneca to develop nirsevimab in a highly successful collaboration. Sanofi Pasteur, as you know, is a global leader in both pediatric combination vaccines and in Influenza vaccines. And those 2 categories do account for about 2/3 of our sales. What does that mean concretely for nirsevimab? Actually, it does mean we have an unrivaled blend of experience to drive the success of this product, assuming, of course, that we go on to receive the expected regulatory approvals. Our experience is based on the deep knowledge of respiratory disease and development of vaccines; our insight into the operating model for pediatric vaccines; our ability to plan and provide effective, seasonal immunization; and our commercial leadership that has resulted in Sanofi Pasteur, building multiple blockbuster vaccine franchise. And we do believe with nirsevimab, we have such an opportunity again. With that, I now hand over to Su that will run you through the global health crisis that is this public health burden.

Thank you, Thomas, and good morning, good afternoon to everyone on the call. To set the context of the event, I would like to share with you a brief video demonstrating the huge burden RSV has on families. [Presentation]

Here on Slide 7, I'd like to illustrate the compelling evidence that the dominant disease burden for RSV is in infants during their first RSV season. By the age of 2, almost all babies and toddlers would have been infected at least once by RSV. With RSV the leading cause of hospitalizations in young infants, there is a clear unmet need for broad RSV protection. And currently, no RSV prophylaxis is available for the very large majority of infants. Slide 8 looks at the U.S. birth cohort of nearly 4 million by gestational age. Less than 2% of infants are eligible to receive the only approved RSV preventative, palivizumab, also known as Synagis. In the U.S., only infants with a gestational age below 29 weeks, or those with congenital heart disease or chronic lung disease, are eligible to receive palivizumab. These restricted recommendations followed systematic evidence review by the American Academy of Pediatrics. Palivizumab also has a burdensome regimen that requires 5 injections over 5 months and carries a list price of $7,000 per baby. As we look to the second and third bars of the chart, you can see the breakdown of the annual number of RSV hospitalization and cost related to RSV hospitalization for the 3 sections I've just introduced: full-term infants, healthy preterms, high-risk infants eligible for Palivizumab. Both the number of hospitalizations and the cost related to hospitalizations are dominated by the RSV burden in healthy infants with up to 80% of the direct costs in this group. There is no vaccine available for this majority of the birth cohort. To summarize, RSV infection does not discriminate among healthy or preterm infants, and any and all infants are at risk. And roughly 98% of infants who are ineligible to receive the only approved prophylactic account for the vast majority of hospitalizations and associated costs. On Slide 9, hospitalizations are clearly an important part of the overall cost of the disease, but they're only the tip of the iceberg, accounting for a fraction of the total cost. In purely financial terms, if we also add in the cost of emergency room visits, loss per rental income, cost of outpatient treatment and so on, the total cost of RSV in the U.S. runs to something on the order of $2 billion annually. And of course, the societal costs run deeper still due to the increased burden on the health care system during the already busy winter season and the emotional impact on affected families, especially those with infants with more severe RSV disease, as we saw from the parent testimony. These slides, of course, only speak to the U.S., where RSV disease is better documented. With current global estimates, industrialized countries face almost 300,000 hospitalizations each year and developing countries approximately 10x that number. When we consider the likely underestimation of the true disease burden due to lack of routine to RSV testing, you'll get a sense of the scale of this public health issue and the significant unmet need globally. Slide 10, my final slide, sets out the value proposition we envisage for nirsevimab, assuming our ongoing Phase III trial successfully replicate the excellent outcomes of our first pivotal Phase IIb study. We're aiming for universal coverage for all infants, irrespective of gestational age or birth month. Our ambition is to achieve a greater than 70% relative risk reduction of RSV-related hospitalizations, consistent with the Phase IIb results you will hear about next. We expect to deliver this with a single intramuscular injection, which will offer a consistent level of passive immunity immediately and over the entire RSV season. And we intend to deliver this in a cost-effective package with a vaccine that is priced in line with other premium-priced pediatric vaccine. Together, we believe this target profile for nirsevimab potentially constitutes a new standard of care in RSV prophylaxis; essentially, a single passive immunization, providing immediate, consistent, sustained protection for all infants during their first season when they're at most risk of infection and complications. We think this profile builds a highly compelling case for adoption in routine pediatric immunization schedules by all relevant payers and advisory bodies, such as the ACIP in the U.S. And as Thomas stated earlier, we, at Sanofi Pasteur have the expertise and the organizational ability to make this a major success and address this long-standing unmet need. With that, it's my pleasure to hand over to Jon.

Jon, you might be on mute.

He's lost his connection.

He lost his connection.

Maybe John Shiver can take it?

Yes. I can do that, and hopefully, John can kick back in. Can you hear me okay?

Yes, we can. Thank you.

Okay. Well, thank you, Su. It's my pleasure now to take you through the exciting Phase IIb results reported in full today in the New England Journal of Medicine. I want to begin on Slide 12 by explaining the innovative construct of nirsevimab and how it facilitates effective and prolonged passive immunization. Nirsevimab is a novel recombinant human immunoglobulin-derived neutralizing monoclonal antibody. It specifically targets a conserved epitope on the pre-fusion confirmation of the RSV Fusion protein, meaning it prevents fusion of the virus with host cells. The smart piece of protein engineering substantially enhances the neutralizing activity of the molecule when compared to palivizumab, resulting in increased potency. The second clever piece of design work in Nirsevimab is a modification of the Fc region, which extends the half-life to between 63 and 73 days. Nirsevimab's half-life extension is critical for our population-based approach. The half-life is approximately threefold greater than the 19- to 27-day half-life of palivizumab that requires monthly dosing, as Su described. In fact, in the Phase IIb study I will discuss the summary concentration of the antibody is still above the target levels in most of the infants treated at 151 days or approximately 5 months after immunization. This time point was deliberately chosen as the average RSV season is approximately 5 months long. Turning to the activity of the molecule. Unlike traditional vaccines that prompt the body to mouse immune response to a foreign antigen, nirsevimab delivers the functional response itself by neutralizing RSV. This passive immunization approach not only provides immediate protection in contrast to standard vaccines, but also as a result of prolonged half-life, it allows once-per-season dosing by a single intramuscular injection. In recognition of the unmet need in RSV and the encouraging early clinical results, nirsevimab was granted breakthrough designation by the FDA and prime eligibility by the European Medicine Agency. Slide 13 sets out the design of the Phase IIb study. This was a large pivotal study in approximately 1,500 preterm infants with a gestational age of 29 to 35 weeks. Unlike the majority of the Phase IIb studies, this study had been designated pivotal by regulatory bodies in the U.S., EU and Japan, and it will be submitted with our 2 other ongoing pivotal studies as part of the registration dossier. The primary endpoint of the study was the incidence of medically-attended lower respiratory tract infections, both in and outpatient, and caused by PCR-confirmed RSV infection for 150 days after dosing. The comprehensive list of secondary and exploratory endpoints included the incidence of hospitalization due to the PCR-confirmed RSV infection, safety, pharmacokinetics, antidrug and antibody responses, health care resource utilization and caregiver burden assessment. You can see from the graph on the right side that the preterm infants were randomized 2:1 to receive a single dose of nirsevimab by 50-milligram intramuscular injection or placebo prior to the start of the RSV season. They were then followed at various time intervals, including 151 days for the efficacy endpoints. As I mentioned earlier, this duration was chosen to mimic the length of the natural RSV season.

John, I'm on now, if you'd like me to take back over.

I would love it, Jon. Please proceed.

My apologies, everyone, for the poor connection here. Thank you, John, for filling in during my difficulties. On this slide, I'm very, very pleased to show you the results of the Phase IIb study that was published today in the New England Journal of Medicine. First, let's focus on the primary endpoints. Here, we're talking about the incidence of medically-attended, RSV-associated lower respiratory tract infection, where we saw a very significant and profound reduction of 70%, from a high of 9.5% in the placebo group, to a low of 2.6% in the nirsevimab group over the entire 150-day time point. This equates to a p-value of 0.001. Now turning to the secondary endpoint of RSV-associated lower respiratory tract infections -- sorry, hospitalizations, the incidence that we saw in the placebo group was 4.1% and in the treatment arm of 0.8%. That's a relative risk reduction of 78%, and again, a very significant p-value of 0.0002. The relative risk reductions for both of these endpoints were consistent throughout the entire 150-day post dose schedule, which, again, conforms to the RSV season in the typical temperate regions of the world. It was consistent across geographic locations, and importantly, across both RSV subtypes A and B, this is very important because you may be familiar with some results of previous studies from other companies that showed a failure to protect against RSV strains. Among other RSV complications, overall, the rates were very low, but no infants that were given nirsevimab were admitted to the intensive care unit or required ventilation assistant as compared with 1% rates in the placebo groups. This is critically important as this is an important consideration in treating these vulnerable infants. Finally, only 0.4% of patients on nirsevimab require supplemental oxygen as compared with 3% in the placebo group, although, of course, oxygen supplementation is a risk for all preterm infants regardless of their RSV infection status. These are very compelling, very consistent and very significant results that led us to believe the hypothesis has been confirmed, and gave us great confidence to proceed in the Phase III and Phase II/III studies. If we can now advance to Slide 15, here, I want to drill down a little bit deeper. Here, we're looking at 2 subsets of subjects both those that were very early preterm infants that were between 29 and 32 weeks gestational age at the time of birth as well as infants that were slightly older, between 32 and 35 weeks gestational age. What you can see here is that the results are very consistent across both groups with either a 74% or a 70% reduction in these 2 populations. Again, the consistency of this data led us to start a Phase III study called MELODY, which John will tell you a little bit more about in some detail, as well as a Phase II/III study in which we're comparing nirsevimab to Synagis. We move now to Slide 16, please. I will focus on the safety data. Here, I'm very pleased to report that the overall safety profile was similar to the placebo group. The incidence of adverse events were similar between the 2 groups, and there were no notable hypersensitivity or anaphylaxis reactions, and in addition, the antidrug antibody rate was very low and was not correlated with any effect on either safety or efficacy over the entire safety readout. Of course, we'll need larger number of subjects to fully address the safety profile of this molecule, and we are looking at that in the Phase III and Phase II/III studies now. Next, on the next slide, I want to point out something that's critically important. Here, I want to compare the possible uses of maternal immunization, like some of our competitors are developing, versus an active immunization in infants, and a passive antibody transfer like we are using with nirsevimab. The bubble that has been drawn on this figure highlights the fact that maternal immunization typically provides protection to infants for a period of time that's about 3 to 4 months following the delivery of that infant. Whereas because we can deliver nirsevimab just prior to the RSV season, we can time that antibody and give a consistent dose that will protect those infants for an entire 5-month season. And this is really the message that we want to share behind the idea that Nirsevimab is appropriate for use in all infants. Maternal immunization brings a number of challenges. First of all, antibody titers are highly dependent on the timing of the mother's vaccination. Second, even with the optimal vaccination timing of the mother, antibody titers are likely to fall below an effective threshold at month 3 or earlier. Now this is critically important if an infant is born out of the RSV season, which remember, is 5 months long. Now active immunization in infant is not appropriate either. Because an infant's immune response is not fully developed at the time of birth, it's not possible to immunize infants at their most vulnerable period of time. Furthermore, even if you were to immunize these infants, you could -- you would have to wait for weeks to months for an antibody response to develop. Therefore, we fully believe that passive immunization with a monoclonal antibody is the optimal way to prevent RSV disease in these infants. The reason for that is because you can give a controlled dose of antibody, and you can time that antibody to occur just prior to the RSV season, and the antibody can provide instant protection to those infants. So therefore, we're developing nirsevimab for the treatment and prevention of RSV disease in all infants prior to their first RSV season, and for infants with congenital lung and heart disease problems prior to both their first and second RSV seasons. If we can move then to the next slide, please. This is a rather complicated slide, and I want to walk you through it a little bit slowly. Here, we're comparing the effect of maternal immunization, where we've modeled a 4-month protective window on the right-hand side, with the use of a monoclonal antibody like nirsevimab with a 5-month window as shown on the left. Now if we focus on the right-hand side, the first thing to notice is the red bands on the graph. Those are the RSV seasons. For an infant born, for example, in the month of September, at the bottom of this figure, they would have a maximal circulating antibody titer that would wane and essentially not provide protection after about December. That means that for a fully half the RSV season, those infants would have suboptimal protection following maternal immunization. Similarly, an infant born in June would gather -- would gain no benefit from maternal immunization because the antibodies would have fallen below the protective level by the time an RSV season even begins. Conversely, on the left-hand side of the figure, you can see that regardless of when an infant is born, a maternal -- a monoclonal antibody like nirsevimab would be able to be given just prior to the season or during a season, if the infant's born during the season, and provide protection for the entire RSV season. Okay. If we move then to Slide '19, I want to get back to a little bit of the data from the Phase IIb study. I mentioned before that we monitored efficacy through the entire RSV season or 150 days. The data from the pharmacokinetic analysis of serum concentrations of nirsevimab demonstrate that the antibody level is above what we determined to be the effective threshold in animal models, which is the dotted line shown on this graph, for about 240 days. Therefore, it is possible that nirsevimab provides protection for a period of time that's longer than 5 months, and this may be important in regions of the world where the RSV season is unpredictable or stretches beyond the 5-month period. Of course, after 360 days, the antibody level has decayed to well below the protective threshold, and that's where we feel a vaccine for RSV can be effective. And John will talk to you a little bit about our vaccine data in a few moments. However, in Phase III -- in our Phase III design, we'll be following respiratory interact infectious beyond 5 months post dosing. Potential for -- to extend this protection beyond 5 months would be very important, as I mentioned, for regions of the world that have longer RSV seasons. Now if we move to Slide 20, please. On my final slide, I want to compare the licensed product, palivizumab or Synagis, with our monoclonal antibody, nirsevimab, and maternal vaccination. If we start with applicability to the annual birth cohort, as Su told you before, palivizumab is restricted because it's dosed on a monthly basis and because of its high cost to a very small subset of infant population. That is about 2% or less, depending on the recommendations in the country. Now that means that, that restriction is to infants that are severely premature, less than 29 weeks gestational age, or have chronic lung disease or congenital heart disease associated with prematurity. Nirsevimab, we hope, will be applicable to the entire birth population. Therefore, protecting the 98% of infants that are not currently afforded either a protective vaccine or antibody and have no treatment options. Maternal immunization is really only applicable to those kids that are born as full-term births or near-full-term births. And ideally those that are born in the season or just prior to the RSV season. If we turn next to the achievable immunization rates -- sorry, Nirsevimab immunization, we believe, could be achieved about 90% to 100% of cases, if added to pediatric schedules. Maternal vaccination really depends upon a variety of factors, including the health status of the mother, and would be expected to be achieved in only about 20% to 40% of women. If we next compare the observed efficacy, we, of course, do not have yet any data showing efficacy of maternal immunization approaches for RSV. However, we do have historical data with palivizumab from 2 studies, which were conducted several decades ago, to indicate that, that antibody provides protection of between 45% and 55% against hospitalization. As you have seen in the Phase IIb data shown to you today and published in the New England Journal, nirsevimab achieved 78% reduction in RSV-confirmed hospitalization. Finally, treatment burden. We've talked a little bit about this before, Palivizumab requires 5 monthly injections and is therefore a burden to parents and to the infants that receive the injections. Unlike palivizumab, nirsevimab will be given as a single intramuscular injection, providing coverage for the entire RSV season. So we at Sanofi Pasteur are absolutely convinced that the immediate controlled protection offered by nirsevimab has the potential to make it the new standard of care for all infants in their first RSV season as well as for high-risk infants in their first and second seasons. And we believe this is a revolutionary solution, providing sustainable RSV coverage for the entire first season for all infants and will provide great value for all of these kids. I hope that the Phase IIb results and the additional discussion I've provided have convinced you of this. And with that, it's my pleasure to hand you back to my colleague, John Shiver.

Thanks, John, and thank you all for taking the time to listen in. I want to make some concluding remarks before we turn the call over to Q&A. On Slide 22, Nirsevimab is a culmination of around 60 years of research and development into RSV. The road here has been especially a long one since the virus was first identified in the 1950s. In the intervening years, multiple preventative approaches have been pursued without success, including investigational vaccines and immunization strategies based around inactivated viruses, viral subunits and monoclonal antibodies. Today, the only commercial available immunization against RSV is palivizumab. This was approved 22 years ago and, as you heard from my colleagues, is restricted to use in a small minority of infants at the highest risk of RSV-related sequelae. So it's been a long wait, but in nirsevimab, we think we finally have the potential for a new standard of care in RSV prophylaxis. The Phase IIb results, as described, met our highest expectations and have provided us with a great deal of confidence in the upcoming pivotal studies. And I can tell you, the excitement surrounding this asset extends to very top of Sanofi. If you listened in to our Capital Markets Day in December, you will have heard our CEO, Paul Hudson, highlighting nirsevimab as 1 of the 6 potentially transformational assets in Sanofi's pipeline. For Sanofi Pasteur, we won't stop there. We want to build a portfolio of approaches towards RSV that additionally covers infants prior to their second and third RSV seasons. To this end, we're investigating next-generation live-attenuated subunit vaccines, which could be delivered intranasally. These are currently in Phase I/II as they're still some years away. Nonetheless, we think they could represent a complementary and comprehensive approach to limiting the impact of RSV alongside Nirsevimab. On Slide 23. So let's move ahead now to our forward plans for nirsevimab. Slide 23 sets out our 3 pivotal studies. The goal of our pivotal program is to generate data across the entire birth cohort for all gestational ages. Our pivotal Phase IIb study discussed today covers the gestational age group that sits in between in the middle of our 3 target populations. 2 large studies are ongoing. The MELODY study is a placebo-controlled study IN approximately 3,000 full-term infants, which is on track for planned completion in 2023. This study will determine the degree to which nirsevimab is able to prevent medically-attended RSV-confirmed lower respiratory tract infections, and it will also confirm the safety profile. The MEDLEY study is a descriptive efficacy study with primary endpoint on safety versus palivizumab in approximately 1,500 palivizumab eligible infants, specifically preterm infants in their first RSV season and children under 24 months with congenital heart disease or chronic lung disease in their first and second RSV seasons. This study, which is on track for completion planned in 2022, will examine the safety profile, pharmacokinetics and anti-drug antibody response as well as efficacy in these high-risk infants. The 3 studies will form the basis for regulatory submissions, which we are targeting for 2023. As I mentioned during the vaccines outbreak at our CMD, this will potentially set the scene for a growth contribution to Sanofi's Pasteur from around 2025. Slide 24 gives you some more detail on our earlier-stage live-attenuated RSV vaccine programs. Here, as John mentioned, the concept is to provide active immunization to infants in their second and third RSV seasons, complementing the use of nirsevimab in the first season. For competitive reasons, we cannot disclose too much information on the construct and planned positioning of these vaccines. However, you can see the graphic on the right side. Demonstrated both safety and immunogenicity in seropositive and seronegative infants as young as 6 months of age. Preliminary data from a study conducted by the National Institutes of Health and Johns Hopkins University suggest that our approach to those antibody activity likely to correlate with protection. So the early signals are promising, and we look forward to additional readouts from the Phase I/II study. Together with nirsevimab, we believe this would comprise an industry-leading portfolio of immunization approaches for the control of RSV for all infants. On my closing slide, I just want to reiterate the key take-home messages on nirsevimab. We're aiming for the cost-effective RSV prophylaxis in all infants irrespective of whether they're pre- or full-term. The data published today from the first of 3 pivotal studies supports our ambition of an approach that aims for 70% to 80% relative risk reduction of RSV complications. This compelling clinical profile will be possible as a single injection for all infants for their entire first RSV season. As Su said, if we meet this target profile across our pivotal clinical program, then we are confident nirsevimab has the potential to become the new standard of care in RSV prophylaxis with broad adoption into pediatric immunization schedules. This, in turn, would finally allow health care systems to address the leading cost of lower respiratory tract infections and respiratory hospitalizations in infants and the resultant infant mortality. With that, I would like to hand over to Eva to start the Q&A. Thank you.

Thank you, John, and thank you to all presenters. Now for the Q&A session, our presenters will be joined by Paul Hudson, Chief Executive Officer; John Reed, our Global Head of R&D; and Jean-Batiste de Chantillon, Chief Financial Officer. Now we would like to ask you for today's call to focus your questions on RSV-related topics. All other questions, we are happy to take on in Investor Relations after the call. So now I would like to hand over to Natalie to remind us how to ask questions.

[Operator Instructions] We are now ready to take the first question from Graham Parry at Bank of America. Graham, please go ahead.

So firstly, I just wonder if you could just help us understand the ability to manufacture this antibody at scale and other costs, which would allow you to come up with a pharmacoeconomically favorable offering to health care systems. Secondly, any data to support the idea that the protective effects in preterm births are translatable to full-term infants? And then thirdly, if you could just remind us of the economics and control of development and sales and marketing between yourselves and AstraZeneca, and any intellectual property on the antibody as well?

Thank you very much, Graham. So just to recap, maybe some of the questions, we'll go to Jon Heinrichs. Especially, maybe, Jon, I know you are not a manufacturing specialist, but you can say a couple of words maybe on manufacturing. And most importantly, on how we move on from preterms to full terms, and a little bit about the IP space. And if you want, I can complete with some elements on the financials of the deal.

No, very happy to. Thank you for the opportunity. The first thing to note is that we are the commercial lead on this product. AstraZeneca remains the development and manufacturing lead. So I would refer questions and specifics about the manufacturing of the product to AstraZeneca. The one thing I would say on that is that we maintain our commitment to making this product available in a cost-effective manner to all infants. So clearly, we anticipate that it will be priced in a way to do so such as in a vaccine, a premium-like vaccine price manner. The second question is, how does the Phase IIb data translate into healthy infants? What I would point out here is that the Phase IIb population, although premature, were healthy, premature and not Synagis population. So they were 29 to 35 weeks gestational age. We believe this is a strong indicator of the efficacy of the molecule for both the Synagis-like population, those very premature infants, as well as is a good predictor of what will happen in the MELODY study in the full-term healthy infants.

And maybe I can complement that on the -- you had an additional question on the financial part of the diagram, if I understood correctly. So as you understood from Jon, basically, this is a profit share, cost share deal. Sanofi will lead the commercialization and, therefore, will book the sales. And in terms of the initial deal that was done, I think, that was communicated that there was a EUR 120 million upfront payment and up to close to EUR 500 million in terms of achievement of different milestones. Next question.

The next question is from Laura Sutcliffe at UBS. Laura?

Do you have any thoughts on the characterization of evidence of antidrug antibodies here? I think your Phase IIb data look quite a lot better than some of your earlier data. And secondly, do you think there's any room to compress the trial timelines here? Do you really need 3 to 4 whole RSV seasons, which I think is what you would have if you took into account both the Northern Hemisphere and the Southern Hemisphere, to get the MELODY trial done? And then maybe lastly, if you do go for a premium vaccine type price, do you worry that a price that low might call into question the price points of antibody used in other areas of medicine?

So maybe I can take the pricing question first and then Jon, I will return to Jon H. -- sorry, we have many Johns. I will return to you on the questions -- on the first 2 parts of the questions. So regarding pricing, great questions. Just to be very clear again, we are 100% committed to make sure that we're going to tackle the burden of disease of RSV. And this is only possible if you take out the burden of disease RSV in all infants. And that's why we are clearly going for a premium price vaccine strategy for all infants. And I think there was a question about, okay, can you be a bit more explicit about what that means? Well, personally, when we think about premium-priced vaccines, I'm thinking about here, it's 1 injection. So basically, it's one injection, which is the equivalent of a full course, I would say, of a PCV vaccine, if you wish, or a full course of HPV. That's the order of magnitude that I consider being a premium priced vaccines. And just maybe to complement that because I think that I've seen some elements recently in the financial publication about this. I will consider that -- I've seen some comparison, for example, to rotavirus vaccines. And for me, it's very interesting to see some comparison with rotavirus vaccines in the sense that it's seasonal. In the sense that in the infant population also. But if you could take a step back and look at the burden of disease, that's very different. The level of hospitalization and the associated cost to this hospitalization for RSV is multiple fold times what it is for rotavirus infections. So again, I think there are some commonalities, but if you think about the benefits this product will bring in terms of really having a huge impact on RSV disease, that's really thinking about a full course of PCV vaccine or a full course of HPV vaccines. That's how we think about the pricing. Jon, you want to tackle the other questions?

Yes, sure, Tom. I'm happy to. The first question related to the data that we saw on the Phase IIb publication on antidrug antibodies, you are correct to say that some earlier studies suggested -- 1 study, in particular, a higher antidrug antibody rate than what we saw here. Here, the rate was very low. I think it's much more in line with expectations that have been seen with Synagis and with other antibody products. What's important to remember is that even when we saw antidrug antibody, it did not correlate with either efficacy or safety. In other words, there were no untoward effects of antidrug antibody here. So we're very convinced that, that's a good signal and a real signal, and that it will remain low in the future. Second question was about time lines. And whether we need 3 to 4 RSV seasons to complete the study. I would say that we're doing everything we can to accelerate this program now. We're considering all possible ways to do that. It's very difficult to predict right now in the face of a COVID pandemic when we can complete the study. And that's really because of 2 reasons: One, it's difficult to recruit and retain patients, and we have to be concerned, first of all, with the safety of these infants and their parents. And second, that circulating COVID and the population response to that really is impacting the spread of RSV throughout the world. So to have a full efficacy readout in this study, we really need to be able to study how the antibody prevents RSV. And if RSV is not circulating in the population, it's very difficult to do that. So right now, we're maintaining the time lines that we've talked about today, and we'll continue to do everything possible to accelerate those time lines because we believe this is critically important to get this antibody out there to begin preventing RSV.

Thank you, Jon. Next question?

The next question comes from Seamus Fernandez at Guggenheim. Seamus? Seamus, you may be on mute. No. Okay. Yes? Please go ahead, Seamus.

Okay. Great. Can you hear me now?

We can hear you.

Perfect. So just one question. It's our understanding that -- can you just help us understand your coverage of both RSV Type A and B with regard to the current antibody formulation? And then secondarily, in terms of some of the older vaccines that we've seen attempted in the past, can you just help us understand whether or not the agency has demonstrated greater flexibility with regard to the types of endpoints. I know it's possible that maybe we see with an active vaccination rather than the nirsevimab passive vaccination that, again, some have shown a reduction in disease burden, but not necessarily hitting the endpoints of disease avoidance or event avoidance. So just love to know where you see active vaccination evolving.

Jon H., I think you might be here again for the story. How nirsevimab is going to prevent both types A and B, and then perceived as active and the perceptions that we target.

Yes. So on the first question, clearly, the data in the Phase IIb study that we released today indicates that nirsevimab is efficacious both -- against both A and B serotype strains. And this is consistent with all the surveillance data that we've looked at preclinically with our collaborators where nirsevimab neutralizes the vast majority of A and B strains that are circulating worldwide. So we know the epitope is highly conserved, and we have no expectation that it will not protect against both A and B strains. The second question, I think, is more about the regulatory environment. And do we expect that there will be some leeway for either vaccines or antibodies that maybe missed their primary endpoints but are close. We don't see that as the case. And we're very happy to say that we have met both our primary and secondary endpoints in this study and that we stand by that data. What the agencies decide to do for other companies that maybe have missed their primary endpoints, I'm not really ready to comment on.

I think if I can add, Jon, whether it's for influenza, pertussis or any of the other respiratory infections, agencies typically want to see lab-confirmed infection rates as well as the prevention of hospitalizations or other outcomes that are also meaningful.

Thank you, Su and Jon. Next question?

The next question is from Mark Purcell at Morgan Stanley. Mark, please go ahead.

Just a couple. Firstly, RSV mutation is an issue here. So this is a theoretical sort of concerns around some of mutations in the F protein, the target of this product. Secondly, just in terms of theoretical safety concerns, both with a vaccine as well as a passive approach, are there any risks on the vaccine side of AED, for example? Just any comments there would be great. And then thirdly and lastly, are there any other diseases where a passive immunization approach would be applicable? And do you have any projects that you could discuss at this stage?

Thank you very much, Mark. Mutations and safety, Jon H., Su or John S. Jon H., maybe start. And then any other project, maybe this one would be for John S.

Yes. So yes, great question. So in terms of mutations in the F protein, so that remains theoretical risk and one that we have to follow. As you know, the epitope that nirsevimab targets is a very conserved epitope. Our colleagues and others are doing surveillance globally looking at strains that are circulating today. And so far, we have a lot of data to demonstrate that nirsevimab neutralizes in vitro, both A and B strains that are circulating to date. What happens once widespread distribution of nirsevimab occurs is -- remains to be seen. But we believe that this epitope is very important to the function of the virus, and therefore, is likely to be highly conserved. The second question related to safety, I think, particularly related to ADE. All I can say is safety is critically important in all of our studies. We monitor that. We have not seen any evidence, either with nirsevimab to date with the vaccine that we're studying, or I think historically, there's no evidence that Synagis induced an ADE response either. So we're very comfortable with the safety profile that we published today in the New England Journal. And maybe John wants to comment on the utility of antibodies for other indications?

Yes. Thank you, Jon. So I mean, I think this is an important of concept for antibody prophylaxis for prevention of infectious disease, certainly pulmonary, but possibly broader. And so it certainly does open the door for additional diseases, and we're evaluating that. Because there is a certain -- a number of conditions that can restrict where this would be truly applicable. And I think perhaps related virus is here to the RSV family is certainly an obvious place to explore it further. In terms of age group, given -- and I know there were some questions about moving to older populations like adults. Actually, the dose of antibody would be so much in an adult population as to preclude the ability to use an antibody in that population. So certainly, open some doors, we think, in certain respects, as I said.

Yes. And not just from a delivery point of view in older adults. But from a cost of goods point of view, I think, would be prohibitively expensive to try and use something like an antibody for prevention of disease in the elderly.

Thank you both. Next question?