Good afternoon, and good evening to Asia. I'm is being recorded. Of Sanofi Investor Relations. Welcome to this event. This is the fifth in a series of five r and d events highlighting the accelerating pipeline momentum building within Sanofi R and D.
Today, we will focus on the phase 2b results of nerzumab, 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'Orchestrament Universelle for a description of these factors.
Next slide, please. So I would like to introduce you to our speakers today. We have here Thomas Trionf, Global Head of Sanofi Pasteur. We have Su Ping An, global head of medical, Sanofi Pasteur. Also, John Heinrichs, global project head nilsverimab from Sanofi Pasteur, and John Scheiber, senior vice president r and d, Sanofi Pasteur.
Thomas will make some introductory remarks and then Soo Ping will describe the major public health burden of RSV, after which Sean Heinrichs will discuss the details of the Phase 2b results. Sean Scheiber will then wrap up with concluding comments, including an update on the Phase III program. We will be joined then for a Q and 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.
It's 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 two b results that you have probably seen in the New England Journal of Medicine. This trial is the first of three pivotal studies for nirsenumab, 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 today the leading cause of hospitalizations in infant in The US and in fact, in many countries around the world. Actually in developing countries, in particular RSV is there a 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 might 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 two categories do account for about two thirds of our cells. 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're going to receive the expected regulatory approvals. Our experience is based on the deep knowledge of respiratory disease and development of vaccines.
Our insights into the operating model for pediatric vaccines. Our ability to plan and provide effective season immunization and our commercial leadership that has resulted in Sanofi Pasteur building multiple blockbuster vaccine franchise. And we do believe with nislelumab, we have such an opportunity again. With that, I now hand over to Sue 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.
Hi. I'm Dina, and this is my RSV story. Winnie was my second daughter, and I had never heard of RSV the whole time that Dylan, my older daughter, was growing up. My doctor described RSV as a cold on steroids. Looking back on it, I would not have described it that way.
I would have described it as a horrible virus that causes your baby not to be able to breathe. They cannot eat because they cannot breathe. You're watching them twenty four hours a day, holding on for dear life until they take that next breath. What I learned from this experience is just how vulnerable babies are. If there is anything that we can do to take this one virus and this one sickness off of a new parent's plate, it's worth it.
Here on slide seven, 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 two, 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. Infants. Slide eight looks at The US birth cohort of nearly four million by gestational age.
Less than two percent of infants are eligible to receive the only approved RSV preventative, palavizumab, also known as Synagis. In The US, only infants with a gestational age below 29 or those with congenital heart disease or chronic lung disease are eligible to receive palavizumab. These restricted recommendations followed systematic evidence review by the American Academy of Pediatrics. Palivizumab also has a burdensome regimen that requires five injections over five 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 hospitalizations and cost related to RSV hospitalizations for the three segments I've just introduced, full term infants, healthy preterms, high risk infants eligible for palabizumab.
Both the number of hospitalizations and the costs related to hospitalizations are dominated by the RSV burden in healthy infants with up to eighty percent 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 ninety eight percent of infants who are ineligible to receive the only approved prophylactic account for the vast majority of hospitalizations and associated costs. On slide nine, hospitalizations are clearly an important part of the overall cost of the disease, but they are 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, lost parental income, cost of outpatient treatment, and so on, the total cost of RSV in The US runs to something on the order of $2,000,000,000 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 US where RSV disease is better documented. With current global estimates, industrialized countries face almost three hundred thousand hospitalizations each year and developing countries approximately 10 times that number. When we consider the likely underestimation of the true disease burden due to lack of routine RNC 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 nosivemab, assuming our ongoing phase three trial successfully replicate excellent outcomes of our first pivotal phase two b 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 seventy percent relative risk reduction of RSV related hospitalizations consistent with the phase two b 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 vaccines.
To together, we believe this target profile for nosivimab 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 are 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 US. 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 John.
John, you might be on mute.
He's locked his connection. He lost his connection. Maybe
John Shiver can take can take it.
Yeah. 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, Sue. It's my pleasure now to take you through the exciting phase 2b results reported in full today in the New England Journal of Medicine. I want to begin on Slide 12 by explaining the innovative concept of dercevimab and how it facilitates effective and prolonged paths of immunization. Dercevimab 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 pelavizumab, 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 sixty three and seventy three days. Nirsevimab's half life extension is critical for our population based approach. The half life is approximately threefold greater than the nineteen to twenty seven day half life of pelobizumab that requires monthly dosing, as Sue described.
In fact, in the Phase 2b study I will discuss, the summary concentration of the antibody was still above the target levels in most of the infants treated at one hundred and fifty one days or approximately five months after immunization. This time point was deliberately chosen as the average RSV season is approximately five months long. Turning to the activity of the molecule, unlike traditional vaccines that prompt the body to mount the immune response to a foreign antigen, nersevimab 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, nersevimab was granted breakthrough designation by the FDA and prime eligibility by the European Medicine Agency.
Slide 13 sets out the design of the Phase 2b study. This was a large pivotal study in approximately 1,500 preterm infants with a gestational age of 29 to 35. Unlike the majority of the Phase IIb studies, this study has been designated pivotal by regulatory bodies in The US, EU and Japan It will be submitted with our two 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 one hundred and fifty 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, anti drug antibody responses, healthcare resource utilization, and caregiver burden assessment.
You can see from the graph on the right side that the preterm infants were randomized two to one to receive a single dose of nirsevimab by a fifty mg intramuscular injection or placebo prior to the start of the RSV season. They were then followed at various time intervals, including one hundred and fifty one days for the efficacy endpoints. As I mentioned earlier, this duration was chosen to mimic the length of the natural RSV season.
Let's see. John, I'm on I'm on now if you'd like me to take back over.
I would love it, John. Please proceed.
My apologies, everyone, for the 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 2b 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 seventy percent from a high of nine point five percent in the placebo group to a low of two point six percent in the nusivimab group over the entire one hundred and fifty day time point.
This equates to, a p value of zero point zero zero one. 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 four point one percent and in the treatment arm of zero point eight percent. That's a relative risk reduction of seventy eight percent and again a very significant p value of 0.0002. The relative risk reductions for both of these endpoints were consistent throughout the entire one hundred and fifty 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 B strains. Among other RSV complications, overall the rates were very low, but no infants that were given nirzivimab were admitted to the intensive care unit or required ventilation assistant as compared with one percent, rates in the placebo groups. This is critically important as this is an important consideration in treating these vulnerable infants. Finally, only zero point four percent of patients on narsivimab require supplemental oxygen as compared with three percent 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 IIIII studies. If we can now advance to slide 15. Here I want to drill down a little bit deeper. Here we're looking at, two subsets of subjects, both those that were very, early preterm infants that were between 29 and 32 gestational age at the time of birth, as well as infants that were slightly older, between 32 and 35 gestational age. What you can see here is that the results are very consistent across both groups with either a seventy four percent or a seventy percent reduction in these two populations.
Again, the consistency of this data led us to start a phase three study called MELADY, which John will tell you a little bit more about in some detail, as well as a phase twothree study in which we're comparing narsivimab to Synagis. If 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 was similar between the two 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 three and phase two three 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 narsivimab. 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 three to four months following the delivery of that infant. Whereas because we can deliver narsivimab just prior to the RSV season, we can time that antibody and give a consistent dose that will protect those infants for an entire five month season.
And this is really the message that we want to share behind the idea that narsivimab 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 a mother's vaccination. Second, even with an optional vaccination timing of the mother, antibody titers are likely to fall below an effective threshold at month three or earlier. Now this is critically important if an infant is born out of the RSV season, which remember is five 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 narsivimab 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 four month protective window on the right hand side with the use of a monoclonal antibody like narsivimab with a five 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 a monoclonal antibody like nosivemab 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 one hundred and fifty days. The data from the pharmacokinetic analysis of serum concentrations of narsivimab 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 two forty days. Therefore, it is possible that nircivimab provides protection for a period of time that's longer than five months.
And this may be important in regions of the world where the RSV season is unpredictable or stretches beyond a five month period. Of course, after three hundred and sixty 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 our phase three design, we'll be following respiratory and tract infections beyond five months post dosing. The potential to extend this protection beyond five 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, palavizumab or Synagis, with our monoclonal antibody narsivimab and maternal vaccination. If we start with applicability to the annual birth cohort, as Sue told you before, palavizumab is restricted because it's dosed on a monthly basis and because of its high cost to a very small subset of the of infant population. That is about two percent or less, depending on the recommendations in a country. Now, that means that that restriction is to infants that are severely premature, less than 29 gestational age, or have, chronic lung disease or congenital heart disease associated with prematurity.
Nircivimab, we hope, will be applicable to the entire birth population. Therefore, protecting the ninety eight percent 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. Nircivimab immunization, we believe, could be achieved in about ninety to a hundred percent 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 twenty to forty percent 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 palabizumab from two studies which were conducted several decades ago to indicate that that antibody provides protection of between forty five and fifty five percent against hospitalization. As you have seen in the phase 2b data shown to you today and published in the New England Journal, nircivimab achieved a seventy eight percent reduction in RSV con confirmed hospitalization. Finally, treatment burden.
We've talked a little bit about this before. Palobizumab requires five monthly injections and is therefore a burden to parents and and to the infants that receive the injections. Unlike palivizumab, nursivimab would 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 nirsivimab 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 would provide great value for all these kids.
I hope that the phase two b results and the, additional discussion I have 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 and A. On slide 22, nirsevimab is a culmination of around sixty 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 palavizumab. This was approved twenty two 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 the very top of sanity. If you listened in for our Capital Markets Day in December, you will have heard our CEO, Paul Hudson, highlighting nirsevimab as one of the six 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 the 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 onetwo, and so 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 three pivotal studies. The goal of our pivotal program is to generate data across the entire birth cohort for all gestational ages.
Our pivotal Phase 2b study discussed today covers the gestational age group that sits in between, in the middle of our three target populations. Two large studies are ongoing. The MELADY study is a placebo controlled study in approximately 3,000 full term infants, which is on track for a planned completion in 2023. The study will determine the degree to which dirsevimab is able to prevent medically attended RSV confirmed lower respiratory tract infections, and it will also confirm the safety profile. The MEDDLEY study is a descriptive efficacy study with primary endpoint on safety versus palabizumab in approximately fifteen hundred palabizumab eligible infants, specifically preterm infants in their first RSV season and children 24 with congenital heart disease or chronic lung disease in their first and second RSV seasons.
This study was on track for completion planned in 2022. We'll examine the safety profile, pharmacokinetics, and anti drug antibody response, as well as efficacy in these high risk infants. The three 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 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 durcevimab 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, demonstrating both safety and immunogenicity in seropositive and seronegative infants as young as six months of age. Preliminary data from a study conducted by the National Institutes of Health and Johns Hopkins University suggests that our approach shows antibody activity likely to correlate with protection. So the early signals are promising, and we look forward to additional readouts from the Phase III 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 three pivotal studies supports our ambition of an approach that aims for seventy percent to eighty percent relative risk reduction of RSV complications. This compelling clinical profile would be possible in a single injection for all infants for their entire first RSV season.
As Sue said, if we meet this target profile across our pivotal clinical program, then we are confident nersevimab 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 healthcare systems to address the leading cause 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 and A. Thank you.
Thank you, John, and thank you to all presenters. Now for the Q and A session, our presenters will be joined by Paul Hudson, Chief Executive Officer John Reed, our Global Head of R and D and Jean Baptiste De Chatignon, 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.
Thank you, Eva. So you have two options to participate in the Q and A. Option one, if you would like to ask a question, please click the raise hand icon at the bottom of your screen. You will be notified when your line is open to ask your question. And please make sure you unmute your microphone.
We are now ready to take the first question from Graham Parry at Bank of America. Graham, please go ahead.
Great. Thanks for taking my question. So firstly, could just wonder if you could just help us understand the ability to manufacture this antibody at scale under the cost, 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 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.
Thank you very much, Graham. So just to recap, maybe, some of the questions will go to, John Heinrich. Especially maybe, John, I know you're not the manufacturing specialist, but you can say a couple of words maybe on manufacturing and most importantly, how we move on from preterms to full terms, and a little bit about the the IP space. And if you want, I can complete with 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 premium like vaccine price manner. The second question is how does the phase 2B data translate into healthy infants? What I would point out here is that the phase 2B population, although premature, were healthy premature, and not synagis population.
So they were twenty nine to thirty five 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 it is a good predictor of what will happen in the MELDY study in the full term healthy infants.
And maybe I can I can complement that on the you had an additional question on the on the financial part of the Deepgram, if I understood correctly? So so as you understood from John, basically, this is a profit share, cost share deal. Sanofi will lead the commercialization and therefore will book the sales. And and in terms of the initial deal that was done, I think that was communicated that there was a €120,000,000 upfront payment and up to close to, €500,000,000 in terms of achievement of different milestones. Next question.
The next question is from Laura Subcliffe at UBS. Laura?
Hi. Thanks for taking my questions. Do you have any thoughts on the characterization of evidence of anti drug antibodies here? I think your phase two b 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 three to four 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 a price that low might call into question the price points of antibody used in other areas of medicine? Thank you.
So maybe I can take the the pricing question first, and then, John, I will return to John h. Sorry. We have many Johns. I will return to you on the on the questions on the first two two 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 gonna take out the burden of disease of RSV. And this is only possible if you take out the burden of disease of 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 one injection.
So basically, it's the one injection, which is the equivalent of a full course, I would say, of PCV vaccine if you wish or full course of HPV. That's the order of magnitude that I consider being a premium price vaccines. And just maybe to complement that because I think that I've seen some some elements recently in the financial publication about this. I will consider that I've seen some comparison, for example, to to rotavirus vaccines. And for me, it's very interesting to see some comparison with rotavirus vaccines in the sense that it's seasonal.
It's 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 for rotavirus infections. So again, I think there are some commonalities, but if you think about the 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 full course of HPV vaccine. That's how we think about pricing.
John, you want to tackle the the other questions?
Yeah. Sure, Thomas. I'm happy to. The first question related to the data that we saw in the phase 2b publication on antidrug antibodies. You are correct to say that some earlier studies suggested, one 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 three to four RSV seasons to, complete the study. I would say that we're doing everything we can to accelerate this program right 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 this study. And that's really because of two 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 timelines that we've talked about today, and and we'll continue to do everything possible to accelerate those timelines because we believe this is critically important to get this antibody out there, to begin preventing RSV.
Thank you, John. Next question?
The next question comes from Shimiz Fernandez at Guggenheim. Shimiz? Shimiz, you may be on mute.
No. Okay. Sorry. Yeah. Please go ahead, Joyce.
Okay,
great. Can you hear me now?
We can hear you.
Perfect. Thanks so much. 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, you know, 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 nersevimab 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. Thanks.
John H, I think you might be here again for for the story. How nirsevimab is going to to prevent both types a and c, And and then about let's see if this is active and the perceptions of the regulators.
Yeah. So so, on the first question, clearly, the data in the phase two b study that we released today indicates that narsivimab is, efficacious 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, narsivimab 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. You know, 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 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, John, you know, 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 other outcomes that are that are also meaningful.
Thank you, Sue and Joan. Next question?
Next question is from Mark Purcell at Morgan Stanley. Mark, please go ahead.
Yes. Thank you very much for taking the question. Just a couple. Firstly, RSV mutations an issue here. So is this a theoretical sort of concerns around mutations in the f protein, the target of this product?
Secondly, just in terms of theoretical safety concerns, both with the 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, John John H, Sue or John S. John H, maybe staff. And then, any other projects, maybe this one would be for John S.
Yeah. So so yeah. Great question. So in terms of, mutations in the f protein, so that that remains a theoretical risk and one that we have to follow. As you know, that epitope that nirsivimab 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 nirsivimab neutralizes in vitro, both, a and b strains that are circulating to date. What happens once widespread distribution of nirsivimab 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, you know, safety is critically important in all of our studies. We monitor that. We have not seen any evidence either, with narsivimab 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've published today in the New England Journal. And maybe John wants to comment on the utility of antibodies, for other indications.
Yeah. Thank you, John. So, I mean, I think this is an important proof of concept for antibody prophylaxis for prevention of infectious disease, you know, certainly pulmonary, but possibly broader. So, you know, it certainly does open the door for additional diseases, and we're evaluating that because there is a, you know, a certain number of conditions that can restrict where this would be truly applicable. I mean, I think perhaps related viruses here to the RSV family is certainly an obvious place to explore further.
In terms of age group, given and I know there were some questions about moving to older populations like adults. Actually, dose of antibody would be so much in an adult population as to preclude the ability to use an antibody in that population. So, you know, it certainly opens some doors, we think, in certain respects, as I said. Yeah. And
and, not just from a 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?
Next question comes from Geoff Porges at Leerink. Geoff?
Unmute? Okay. I think I'm unmuted now. Yes. First of all, congratulations on the data.
Seventy percent reduction in in hospitalizations and symptomatic cases is is very impressive. Now RSV has been a holy grail for the pediatric world, and I'm not sure I would be generous enough to say this is truly a vaccine, but regardless, pre exposure treatment is is very positive. Several questions. First, could you clarify how you will explore the question of what effect this has on the later epidemiology of the disease and exposure? How, for example, do you know that school age infants and young children won't get more severe disease after they've they've been treated with with this antibody?
Secondly, do you have any data on whether this could be used in treatment when you've got a confirmed case? Obviously, you might need a higher dose, but but it would seem sensible that you could treat an infant who developed symptomatic disease. And then lastly, are any of your prophylactic vaccines, your active immunization vaccines being studied in school aged children or the elderly? Thanks.
So maybe for the first one on the the expected effect on little AP or exposure, maybe Sue, you can take this one, and then John for the the treatment options. Yeah. So John H. Sorry.
So so so for sure,
we know that the RSV the natural history of RSV is that, actually, we don't expect lifelong immunity. I mean, we can get infected with RSV several times through our life. But what we do know is that it's actually, as we saw from the data, that u shaped curve with the extreme ends of the of the age spectrum where the severity occurs in the very young and the very old. So even if you felt that if we if we believe the hypothesis that perhaps you delay an infection into the into an older child, we know that older children are going to their respiratory systems are already going to be more mature, and they are less susceptible to a more severe disease. Of course, we will be monitoring that, but we certainly also that was one of the reasons that we have the full program that is anticipated to help bridge them from the first year of life to the second and third year of life with vaccine options.
And, of course, related to the the older age range, we we also wanna make sure we can actually help address quite a sizable burden there as well in the seniors in together with flu, RSV, and, of course, now with with COVID, these are all RNA viruses that can cause considerable disease at that end of the of the age spectrum.
Yeah. And I I think the next part of the question was about treatment, and we don't currently have any plans to study nircivimab for treatment. I think there's two avenues to argue against that. One is the biology of the virus and targeting the fusion protein, which as you remember, causes the fusion of the viral membrane to the host cell membrane. It's unlikely that once an infection is established that you'd be able to access that fusion protein because most of the transmission, of the virus from cell to cell occurs across the cell membranes.
So unlikely that treatment would work. The second piece is that that's been studied with other RSV antibodies and has not shown to be efficacious for treatment. And I think maybe John Shriver wants to speak a little bit about, active immunization for older kids and the elderly.
Yeah. So, you know, we do, as we showed, have a live attenuated actually intranasally delivery candidate for, you know, second season and beyond for children. And that's what they do in gender active immunity. They're developed better immunologically. They should respond better to the vaccine.
And as we showed, there's, you know, data that's anecdotal at this point that the versions of the vaccine that we're working with that came from the NIH can be looked like they can be quite effective and safe in that population. Now, so that's the reason for how we're covering the pediatric population. In the elderly, it probably takes a different kind of vaccine approach than the ones that we're talking about for children. If you put a live attenuated vaccine into an older adult that has sub preimmunity, you'll probably neutralize that vaccine immediately, and it won't be effective. Now that's an important population to target.
We are working in that area as well. And, you know, we hope ultimately to be able to have a comprehensive strategy for RSV disease across these populations with these several products or product candidates.
Thank you. Do we have a last question maybe?
So we can take a question from Peter Verdult at Citi. Pete? Pete, make sure you're on mute you're on mute your phone. Okay. So let's try Luisa Hector at Berenberg.
Luisa?
Hello. Thank you for taking the question. I just wondered whether you had approached the regulators about filing on the phase two b data. And then maybe just to to check because obviously there are some maternal vaccines maternal vaccine studies that are ramping up as well. So does that add an additional challenge in terms of your recruitment, or are there enough patients to go round?
And do you think the antibody could could yet be used in infants from mothers who had been vaccinated?
John H. And with the support of John H. Do you want to take those questions?
Yeah. I think, maybe I can start in in reverse order. The question about do we think that the antibody could be used in the infants that are delivered to mothers that have been vaccinated? We do not expect that that antibody would be interfered with by maternal vaccination. That, of course, would have to be established, clinically.
We are ahead. Right? So I think the burden will be on them to show that there's no interference there. But the second question was about have we considered approaching the regulators with the Phase IIb data for licensure? We could do that.
The study would support most more than likely licensure. The safety database would likely not be sufficient. We'd have to do some additional safety analysis. The real problem is that this study was conducted in a very small subset of the infants. So the indication that we would likely receive would match that which was studied, which is infants that are between 29 and 35 gestational age, thereby leaving out the majority of infants that need to be treated.
And there was one more part to that question, I think, Tamar.
Recruitment challenge. Recruitment is Recruitment fine.
Know, so far, to date, we found that parents and providers are enthusiastic about volunteering for the phase three MELEDY study. We don't foresee a problem there. You you know, we, before COVID hit, at least, we didn't anticipate issues for recruitment. So we don't know what'll happen when the maternal vaccine comes into the clinical studies, but we'll have to wait and see.
Mike, remember, very few you know, there there are no real options other than palliative for treatment. And this is an extremely common disease in this infant, you know, young child population. So, you know, without an alternative, it be it does and the commonality of the disease and the severity of it, it makes it much easier to recruit under normal circumstances. You know, we'll see how we're gonna deal with COVID. Sue, I'm sorry.
Go ahead.
No. I think, you know, I've previous experience with maternal immunization trials. It's actually very difficult to enroll pregnant women into those studies. And and, you know, of course, we have the timing considerations that John highlighted as well. On the other hand, you know, when you see the parent stories that that were was shown earlier, you know, people are very enthusiastic about enrolling for for study with the monoclonal antibody approach.
So so I think, of course, it remains to be seen if if we end up in the same sites or the same countries, but I I I would not anticipate recruitment challenges.
We do have the sample, you know, efficacy study already, which does not exist, as John highlighted, and Sue did as well for the maternal.
Yeah, and the other point to make there is that between the MELDY and MEDLI studies that are ongoing, we have somewhere around 300 sites enrolled across both the Northern and Southern Hemispheres and I forget how many countries in total. So we have broad representation which allows us to kind of flip between countries, and sites, if we have a recruitment problems on on one site.
Thank
you. Next question. I realized there are many more questions. So so we'll go we'll get through all of them. No worries.
Thank you, Thomas. So the next question is from Vimal Kapadia at Bernstein. Vimal?
Oh, great. Thank you very much for taking my questions. So just just coming back to you mentioned the premium pediatric pricing structure. I So guess I just wanted to hear any feedback you've had from governments and purchases from such a strategy given, you know, that's the complete opposite of what we saw with Synagis, which was priced much more like a like a drug. And then tied to that, can we really expect to see penetration rates similar to other essential pediatric vaccines of greater than 90% assuming that price point?
You know, how far can nisemumab actually go in these high income countries? And then how much of an opportunity is is it in lower income countries? You know, should we thinking should we be thinking similar volume value mix across countries as other vaccine markets? And then just a final clarification question from an earlier comment. You suggested PCV and HPV as a good benchmark.
Should we think be thinking similar price per dose or or should we be comparing against the full dosing schedule for those indications? Thank you.
Thank you, Vimal. Clearly, for a full course of of those comparisons as examples of what are premium price vaccines. So so here we found out that nirsevimab is so great, but you need only one shot to to get prevention. But but the idea is to get prevention. So so so so we are comparing it for for the full course, of course.
To your questions, of course, it's it's it's it's clearly and we are just publishing a phase two b results to to have in-depth discussions about pricing with the so these are still early indications. But I do believe when you look at the impact of the disease, and we've had some mention of that before in the presentation from Sue, but there is a significant burden of disease. And again, you can think of very, very significantly higher in terms of number of hospitalization, for example, than rotavirus, and and that gives you an idea. And you see very high vaccination rate against all that virus. So so remember, this is the number one cause of hospitalization for infants in The US.
And you've seen before the rates of hospitalization for this disease, especially in the 11 years of age. So so we we do believe that is a very important burden of disease. We do believe that not all procedures will be equal and this one in a one shot molecular antibody that is precisely giving you the protection at the time you needed with immediate onset is the right way to tackle this problem. So therefore, we do expect a significantly high vaccination coverage rate or immunization rate, if you wish, especially in high income markets. And and to have an idea, if you think about just Japan, EU 5, and and The US, we're taking about eight million newborns per year.
So so so we we do believe there is significant potential there.
Right. And and I think there was a comment earlier. This is considered as a holy grail, and as Thomas highlighted, this has been long anticipated and and much needed. When we've been interacting with some of the stakeholders like the, you know, the ACIP equivalents in in in these countries, they've been extremely enthusiastic, wanting to know the data, really highlighting they know their own data. They have a huge amount of respect for the burden that this RSV causes in the very young infant population and are very, very much looking forward to seeing the data coming from from our development.
And of course, the anticipation of the value is is is is in line with the very nice phase to be results that you have seen. Again, the the huge impact on the specialization or infection is is very, important. And and and these recognitions we believe is also established by the fact that we have the breakthrough designation from FDA or the prime status at the amenable.
Thank you so much.
Thank you. Next question.
So the next question is from Peter Dutt at Citi. Pete?
Second time, Lucky. Can you hear me?
I can hear you.
Alright. Good. Good. Just two. There's been so many, but just a clarification and and an invitation.
Just to confirm, are you is the antibody hitting the F protein in the the pre or post fusion confirmation? And then when we look at some of the, you know, competing approaches out there, you got companies like Bavarian Nordic doing a multiple protein approach, GSK talking up their RSV vaccine candidate. Any observations or compare and contrasts you'd be willing to share with the audience? I'd be interested in to interested to hear. Thank you.
John H, do you want to take this one, pre fusion or not? And and
That's the easy that's the easiest question so far, Tom. I'm glad to take it. The, antibody narsivimab is specific for pre fusion f.
The second part of the question was about the if I understood correctly, Pete, about the comparison with your approaches from the competition. Correct?
Yeah. Any any observations you're willing to share? I realize, you know, probably don't wanna say much, but anything you're willing to share?
For me for me, I I I don't know if we with projecting the slides, if we go back to slide 20, and I take that occasion. Sorry. As mentioned before, we are very, very, very excited today because RSV has been for a long time the next big target in vaccines. And we do believe that those results that have been have been published today in New England Journal of Medicine are pivotal and critical because it's gonna be a huge change in the way we prevent this disease. We have we have no way to do it except for the one point six or two percent instance that we are in the indication of bivizumab.
Here, we have now a way to do it for everyone. And I think that's the very, very important part. So so, of course, if I were you, I will look at the recent news and say, okay. Yes. It's the next best best target in vaccines.
Yes. It's coming soon, but there are many players down the road. So you've heard about all the phase one, phase two, phase three candidates that have been announced. You have Merck, you have Pfizer, you have g s GSK, you have J and J, and and probably some others. But I'd like to highlight one thing is that not all approaches are the same.
And we do believe this slide that you have here in front of your eyes is very important to mention that. We do believe that the the benefits of nirsevimab that you see in the middle is unprecedented when you compare to the other approaches. And maternal immunization, which a few of our competitors are pursuing for the same indication, protecting the early infants is very, very different. Methanol immunization is not new in terms of procedure. You know very well that we know methanomization extremely well because we we do it.
We have a vaccines. We have influenza vaccines that are both in various countries recommended for our maternal mutations. But even the highest rates in those countries for maternalization are actually low rate and nowhere comparable to classical VCRs that you get into injecting into a young infant. So so when you want to be tackling the burden of disease of RSV, I I think it's very important to look at how you do it best. And then you look at these numbers and see the ways the impact can add is very different from one approach to the other.
So so you multiply that by the fact that it's a seasonal disease. And therefore, if you think about it, you would not give a flu shot to your to your parent in the month of April if you're in the Northern Hemisphere season. So same thing here. You don't control when pregnancies will happen during the year. So so really, I think that the impact you can seriously get into meta normalization for this disease is highly questionable.
Nirsenumab is able to with a proven now phase two b demonstrated efficacy to really tackle this disease in a way that no doc can do. Thank you. Next question.
And so we will end the q and a with Simon Baker at Redburn. Simon?
Thank you. Thank you very much for squeezing me in. Two questions. Firstly, I wonder if you could share any of the health economic data that you have. As you say, the the the prevalence and and cost of of hospitalization in this in this setting is is pretty high.
So I would have thought that the at the price point that you're talking about, the health economics are overwhelmingly favorable for the product. So any details you could share there would be would be much appreciated. And then secondly, do you perceive any logistical challenges in the real world setting with folding nasevimab passive immunization into existing vaccination strategies, which are typically quite well defined time points, whereas this won't be because of the seasonality of the disease. Associated with that, can you give us a reminder of the typical time from approval to inclusion in vaccination schedules in the major markets? Thanks a lot.
Thank you, Simon. Sue, do you want to take those first about the implementation in the real world setting and how do you see it and and maybe some elements about health economics?
Right. I I think it depends, of course, on on which countries we're speaking to. But, you know, countries generally have very, very good access to infants throughout the year. Right? There are time points for vaccination in the first six months of life.
There are also well baby visits. So, of course, there's a timing aspect with respect to the season, but given the the numerous time points that a mother and the child will be accessing their physician or or health care provider, I believe that as long as the the programmatic aspects are well explained to the providers, and the public health system is rolling it out, then there should be a a lot of clarity in terms of how and when to deliver the dose of pasugamab. So I think, you know, from a real world standpoint, there are enough time points for access to address this issue.
Thank you very much. Any other question or was this the last one?
It was the last one, Thomas.
Okay. Again, just to conclude, maybe a few words. First of all, thank you very, very much to everybody for attending. We do believe again, as I said at the intuition, that this publication is really a landmark in making sure that now we have a way to tackle RSV disease for all infants and not just a few selected part of the newborn population. I think it's a huge padding shift and it's gonna be able to do it in one single injection that can be even at the time it's most required.
And again, if you look at it from a programmatic perspective, logistic perspective, efficacy perspective, safety perspective, this is a very, very promising asset and we're highly excited by it. You probably understood that today. That that's the first point. Second point, I would encourage you to discuss about RSV or bronchiolitis with whomever you're encountering around the room in every single setting during the vacations because you're gonna see that it's highly highly frequent disease into the all newborn population. And my my daughter, now turning 15, has been immunized when she was just turning three month of age for three nights in the hospital here in Lyon, and I don't wish it to anybody as you've seen in the video.
This is a real problem. It's the a bit the holy grail of vaccination has been discussed for many decades, and now we are touching from from our finger points the way we're gonna be able to tackle this disease. So so very, very exciting news. We do believe it's a great asset. They are still, as mentioned by the team, two more pivotal studies to come that are running and and the results are expecting come to come soon.
It gives us also a bit more time to keep explaining the importance of nercimumab and the burden of disease of RSV to make sure that as soon as we are licensed, we are in a position to make sure that as many kids as possible, all newborns, all population are protecting against this severe disease. Thank you very much. We're looking forward to further exchanges with all of you about RSV disease and nirsevimab in in particular. Thank you.