Sanofi (SAN) Earnings Call Transcript & Summary

To kick off. So welcome to the next session. I'm very pleased to be able to have from Sanofi with us today. Two different areas to talk about. So we'll probably try and split the timing roughly equally between the two. So we have Naimish Patel, who's the Therapeutic Area Head, for Immunology and Inflammation. And then François Sandre, who is the Head of Vaccines in Europe, so probably two the core pieces of Sanofi that we can get to discuss here. So welcome. Thanks for the time today.

And I might kick off on the Immunology side with you, Naimish. So obviously, one of the biggest and best drivers of Sanofi at the moment is Dupixent across multiple different indications. So quite a tough act to follow if you're looking at developments. But perhaps you can just run through where you see where, particularly in atopic dermatitis to start off with the level of unmet need and where the gaps in the market that you're looking to address to Sanofi development.

Yes. Sure. Absolutely. Great question. So atopic dermatitis is maybe the easiest way to contextualize a parallel to psoriasis where there's 7, 8 mechanisms in that space and atopic dermatitis is actually more common than psoriasis. The number I remember off the top of my head is 1.9 million moderate-to-severe patients in the U.S. alone. So it's extremely common disease. And Dupixent, obviously is a fantastic product. The mechanism of dupilumab is targeting the IL-4 receptor, which is very specific and potent for type 2 inflammation but in terms of comparison psoriasis, atopic dermatitis is a more heterogeneous disease in terms of the underlying biology. Some patients have a mix of inflammation, type 2 plus type K17 some people have described as almost psoriasis like in terms of the way the rashes. And then it really depends on subpopulations, different ethnicities, different age groups have different driving biology. So dupilumab, of course, is fantastic efficacy. The IgA-01, the patients of clear -- almost clear skin is around 30%, 35%, but that leaves us a large swath of a population that has responded partially or incompletely. And we think maybe different underlying biologic drivers are in part, responsible for explaining this. So a mechanism like amlitelimab, which targets both type 2 inflammatory pathways, but also type 17 inflammatory pathways. So the potential to be complementary and address slightly different populations because unlike psoriasis, we're the same population we're just building on the next biologic that's even more effective. I see atopic dermatitis having a variety of mechanisms that probably address different subpopulations. And they might not be identified necessarily by biomarker strategy. It might just be a little bit more trial and error going across. But I think that is one area of unmet need. The other one, if you look at psoriasis, what really opened up that market for advanced or better penetration where it's 30%, 40%, where today in AD is around 12% is the available of safe oral. So a lot of patients with moderate disease either are unwilling to go on to biologics or maybe aren't even eligible for a biologic. And so an oral drug is very impactful in pulling more patients into the advanced therapy market, and then they might go on to a biologic after that if they get it in complete response. So we see a definite need for a safe oral in atopic dermatitis. We have a couple of things there with rilzabrutinib and also our Kymera IRAK4 going into that space. So I would summarize the unmet needs in atopic dermatitis. There's still plenty of room to grow, plenty of mechanisms to increase penetration, the need for differentiated mechanisms, better efficacy and also something for more moderate patients.

Got it. And a few assets essential we'll get on to. And I think quite an invest focus there is also competition in the atopic dermatitis market as well. We've seen the launch of JAK inhibitors, we will see the launch of lebrikizumab, so we've also got to bring in the market so perhaps you just run through where you see the differentiation for the competitors or where you think Dupixent perhaps has the best profile in the market.

Yes. No, absolutely. I think if you look at across the indications, IL-13 blockade enough probably doesn't sufficiently or potently block type 2 inflammation. So you've seen the efficacy of dupilumab in multiple diseases where the IL-13 have shown some efficacy, but not enough to even get to market. So beyond AD, its asthma, it's EoE where IL-13 have tried but incomplete. And then that really speaks to the need for the dual targeting to get the most potent effect in terms of efficacy. The numbers for IL-13 look pretty good in terms of atopic dermatitis, but it's -- at this point, it's hard to do exact cross-study comparisons because they're coming so many years after dupilumab being on market. When dupilumab Phase III studies were done, there were no advanced therapies beyond broad immunosuppressive. So you have the sickest of sickest patients participating in those trials and us getting really great efficacy, where now you see many of those sick patients are already on dupilumab, so that are not coming into clinical trials. It's generally a milder population. And so not easy to do cross-trial comparisons. But if you ask prescribers today, there's dupilumab still is the go-to in terms of both efficacy and safety in the AD market.

And I think one of the things is the potential to have 4 weekly rather than 2 weekly administration label. When you're looking at development, how important do you think it is to have different or less frequent administration with the auto-injectors?

I think less frequent administration is something that could make an impact and it is important. But I think the difference between 2 and 4 weeks isn't really a huge difference. I mean going to something much less frequent is potentially more impactful but I don't see that as being a huge differentiator, 2 to 4 weeks. It's not that different.

Got it. So you touched on amlitelimab and the potential to have a broader mechanism of action. Perhaps you just dig into that a little bit more. So what's the evidence for broader mechanism of action, both from a biomarker point of view, but also from any kind of clinical efficacy point of view.

Yes, great question. So it gets back to the fundamental mechanism of amlitelimab which is blocking OX40-Ligand. This is an inducible ligand on antigen-presenting cells at the sites of inflammation that will activate both T effector and T memory cells. And I was in like the analogy of immune response to like an emergency response team like firefighters and say you have this a town atopic dermatitis, where you have a bunch of firefighters and there's fire alarms going on at houses all over the place, and they go to these places. They spray the house down, they cause all kinds of damage because they think there's a fire there. But there's no real fire. In the case of atopic dermatitis as a body being fooled into activating an immune response that is supposed to be directed toward parasites. But in that case, cytokine blockers, what they do is cut the alarm and so the firefighters are still sitting in their -- the firehouse, but they're not necessarily going to put out a fire. But the problem or the problem could be there is that if you stop the drug temporarily or you have some stress or response, you can have breakthrough and then all these firefighters suddenly activate, and you get the whole disease coming back very quickly if you ever stop the drug or try to less frequently dose. What OX40-Ligand does is actually downsize the fire department to be much more fit for purpose for what's going on. So immuno modulation, essentially. So if you do get a trigger, or if you infrequently dose the drug, there's way fewer firefighters and they're not -- the whole disease is not going to come back so quickly. And the evidence for this clinically was in the Phase II study of amlitelimab, where when patients were moderate-to-severe AD patients were dosed with 12 weeks, you got a greater than 40% production in IgA or IgA response or IgA-01, at the end, so greater than 40% of patients were -- had a clear or almost clear skin by the end of the trial. The interesting thing for that trial is we also follow those patients off drug for up to 6 months, and 70% of those patients off drug still had a durable response. So the disease does not come back. So very well supporting evidence that they're really resetting the immune system. And so I think this is a potential real differentiating factor for amlitelimab, both in terms of what I mentioned before about getting different types of inflammatory responsibles type 2 and non-type 2 but also resetting the immuno response that you can dose quite infrequently. If you contrast that mechanism with the other biologics targeting the receptor, it's really a different approach in the sense that a T cell that's away from the site of inflammation, it's -- the antibody only gets an antigen-presenting cell expressing ligand. It doesn't affect that T cell. So in contrast, the ones targeting the receptor will actually deplete by standard T cells and also deplete regulatory T cells that might be one important for fighting infection, but the regulatory T cell is also important for maintaining efficacy we think the ligand targeting strategy is a better way to target this pathway. And one of the examples of this is that when you have a cell depleting agent, you often get cytokine release-type reactions, fevers, chills, and you see this in some of the studies with the receptor targeting biologic and you don't really see it with amlitelimab.

So some of the push probably you've had on the idea that this is differentiated or broader pathway coming from KOLs is that if that was the case, then you'd expect it to have a better, easy response rate or IGA response rate. But actually when you sort of try and compare cross-trial amlitelimab similar to DP but just with a much longer duration of action, which sort of speaks to potential disease modification. So -- and is that -- how would you counter that argument? So why wouldn't you -- why didn't you see in that Phase IIa, just a better response rate, more patients responding if you have a broader mechanism.

Couple of things. I think because of the nature of the mechanism, you will actually keep seeing improved response over time because you're not directly hitting the alarm, but you're actually downsizing the fireman and that takes some time. And I also think, I mean, dupilumab for those patients that are largely purely type 2 is still the most potent type 2 agent. So it's not surprising that within a segment it's still highly effective and amlitelimab is just moving over to a different segment that's also quite effective. So I think for a certain segment of patients, dupilumab will still be probably the best drug for them, but I think a different segment for frame amlitelimab.

Got it. And so you've got the Phase IIb data in-house, which is subcutaneous dosing. Perhaps you can just help us understand the difference in the trial design for that Phase IIb versus the Phase IIa other than just the administration and so what do you think that was intended to yield in terms of differentiation on results versus the Phase IIa?

Absolutely, great question. So it's a Phase IIb study, so it was a dose range finding studies, so we have multiple arms with different doses. And also it's a longer-duration study. So the Phase IIa only dosed 12 weeks and then had a readout of 16. This is actually a readout at 24 weeks, getting to that point I mentioned where we might continue seeing improved efficacy over time. And also, within that study, we had a -- after the 24 weeks, the patients who are responders, we randomize them to continue their regimen or withdraw or stop the drug. And that's a way of us understanding much more in a randomized way what the duration of response will be off drug compared to patients who are continuing it. So much more sort of a controlled way of actually saying, yes, out to 24 weeks compared to patients who are continuing drug, this is what the response in patients who are off drug. And that will really inform both in terms of if we either have a maintenance induction regimen, what the -- how might we dose in a maintenance regimen, but also can we fundamentally start with a different dosing regimen upfront. These are sort of the questions we're considering. We don't have answers for them yet still data coming in, but we intend to start the Phase III by Q1 of 2024. So we'll have much more definite answers on what kind of dosing or the frequency dosing, things like this by that point.

Got it. Okay. And when we think about the -- sort of the dose that you did, I think, in the Phase II was monthly dosing and -- but then -- so on the maintenance period, was that 3-monthly dosing afterwards as the regimen in the maintenance period.

No. In this study, it just withdrawal versus the same dosing. But I think both having different doses at Q4 because you can match exposures to lengthening dosing, but also the withdrawal period. Both of dosing add information about how -- what kind of actual dosing period and dosing intervals we could eventually have.

Got it. And I think you're really an asthma, so where you have gone for a 3 monthly dosing. So what was the rationale behind that versus doing monthly dosing for atopic dermatitis.

Yes. I mean, asthma is -- it's a little bit more of a periodic disease. So we were a little bit more aggressive in saying, "Hey, let's potentially consider Q12 dosing in asthma for maintenance with an upfront Q4 regimen. Because in AD, the disease tends to break through much quicker when you stop, we have two different designs because in asthma, we thought we could even get there sooner. But the potential is that for both will probably potentially land in the same place. We'll see.

Okay. So potentially, up to 3 monthly dosing or on the profile, so you could even be longer than that for Phase III?

We'll have to see. I think from asthma, I think it's clearly a Q12W would be something to think about.

Okay. One of the things when you're bringing a new drug into a space often that you can bring differentiation on this safety Dupixent probably one of the biggest selling points is safety. So how do you see the safety profile of amlitelimab, especially given sort of broad mechanism versus Dupixent?

Yes. So far, I think from what we released in the press release over the summer, the drug has been very well tolerated out to the 24th week duration that we had in that the Phase IIb study. So we're very potentially hopeful that we could have a great safety profile. To contrast that, I think some of the other OX40 receptor agents, not only fever, chills, but also other things that could be indicative of T cell depletion. We haven't seen that with our drug. So hopefully, we have sort of threaded the needle there with something that's efficacious but also more modulatory and potentially well tolerated.

And do you think we'll see the Phase II data ADV?

Not ready to say that yet, but at a medical conference, hopefully, in the second half of this year.

Got it. Okay. I'm going to quickly wrap through a couple of the other immunosuppressants because you want to get on to vaccines as well. So if we look at rilzabrutinib is the other product where we could get some Phase II data fairly soon, you talked about oral being the other sort of part of the segment of the AD market where your -- there's an unmet need. You're also running CSU asthma as well. But obviously, BTKs have a liver issue. So perhaps you can just put us -- put the context of rilzabrutinib into a class that looks like there might be a liver safety issue? And what do you need to show on safety in the oral agent to work in atopic dermatitis?

Absolutely. I mean, the nice thing about rilzabrutinib is it's a different type of molecule in terms of the tailored covalency so there is a in the small molecule, there's an area that binds to the kinase domain that actually inhibit a molecule, but there's another binding domain that gives it a little bit more specificity and less risk for off-target effects. And that second binding domain also increases the residence time on the target without requiring systemic exposure. And so having that specificity and increased residence time potentially will drive safety differentiation in terms of sitting on a BTK, but not sitting on other off-target effects that may drive some of the liver effects we're seeing with -- many of the others are irreversible. And so this when you also stop it, the drug goes away. So we think there's potential for safety differentiation in assets versus other BTKs. We'll have to see where the data lead us. And the interesting thing about the BTK inhibitors and driving very quite diverse diseases, right? We're talking about MS, which is a B-cell driven disease. And other autoimmune diseases, but then also CSU, which is a mast cell-driven disease. And because of the fundamental importance of BTK and not only driving B-cell differentiation signaling but also IgE signaling on mast cells. So allergic and atopic inflammation and that's part of the underlying rationale for studying in not only CSU, but asthma and AD. Obviously, CSU is probably -- has been validated by other BTKs. So we're hoping to see -- we should see positive data on that. Asthma is also partially a mast cell-driven disease. So there's more validation. And if you take Xolair, which has many of the common signaling pathways as a BTK inhibitor, we should see a signal there, but we'll have to see. And AD is probably the one that has less validation. Xolair is not an AD and slightly different signaling pathways. But mast cell, there's a lot of literature suggesting mast cells, especially contribute to itch in AD. So we'll have to see where the readout leads us and it will be in the second half of this year that we're ready to share those data, but we're looking forward to it.

And you've had a failed study in pemphigus. Does that sort of dent your enthusiasm in dermatological setting, here perhaps just compare and contrast study design, indication versus AD.

Yes. No, that's a great question. I think pemphigus the study was something Principia design. And if I were to go back, it should have been a longer study. And the reason is that in that treatment paradigm, we're treating on top of steroids, so even the placebo patients were getting steroids, which that disease pemphigus is very responsive to. And it -- on general, it took about 6 months to withdraw steroids even on the placebo patients. And so it's not long enough to see a difference of the drug if you're -- if it was only a 6-month study, the full duration of the study withdrawing steroids. So I think there are definite biomarker signals that of activity. We saw a decrease in the anti-DR3, the pemphigus auto antibodies in that study that the drug was having effect. And maybe if it was a bit longer, we could have seen. So I think we're still quite confident that the drug is an active drug. And if we designed the right trial in the right diseases, we're going to see efficacy.

Got it. And itepekimab, we just have Roche here talking their SD1 just compare and contrast that what we see with Astra, we see with the Roche SD1 and pathway receptor inhibitor. How you see IL-33 and your IL-33 in particular, competing in those products on profile at least?

Yes. I mean the -- so we're -- of course, dupilumab will get the type 2 we're seeing it as getting the type 2 COPD population, which is about 1/3 of COPD, but the majority of COPD is non-type 2 COPD, low eosinophil count and with itepekimab the only one to have this large study in Phase II in COPD, what we saw in that study in patients who are already on inhaled therapy. A greater than 40% reduction in exacerbations, which is a fantastic, a huge number in patients that are already frequently exacerbating despite inhaled therapy. And that gave us a lot of confidence where unlike dupilumab when we staggered the 2 Phase III studies and had an interim analysis, we started both Phase III studies concurrently. And today, it's the only IL-33 with data in COPD. Roche with anti-SD2 does have data, but significantly 80-patient trial, much smaller than 300-odd patients we had for itepekimab. And this -- earlier this year, we also had similar type of futility interim analysis, and we announced that we passed that. And so we're really excited about the potential here, and we have the best data to be even able to look at subgroups where the Roche study could not really do that. And we think we have the right population of patients or former smokers, irrespective of baseline eosinophil status. And that, together with dupilumab, potentially get greater than 80% of COPD patients were today, third leading cause of death. There's really no new advanced therapies in years and years and years.

And there's lots more assets for itepekimab, so I'm just going to ask one more because I get asked to ask that, is the oral TNF. Just rationale for going oral in a market that is very well served in going biosimilar.

Yes. So I think, first of all, being in science, I have to start with the mechanism, which is really interesting. And this was a difficult compound to develop many failures because of preclinical toxicities and off-target side effects but we finally got to a compound that -- what it does is it actually -- TNF exists in the blood as a trimer that binds to TNFR1, and TNFR1 is a receptor that generally causes most of the inflammatory effects of TNF. And what this compound does is bind that trimer and change the 3D confirmation, so it no longer can signal through TNFR1, but it leaves TNFR2 intact, which binds to membrane-bound TNF. And the beauty of that is that we demonstrated this in preclinical models where you can get efficacy equal to an anti-TNF in an arthritis model and equipment to a biologic. But if you look at a model of bacterial infection to see the effect on immunosuppression that this molecule because it leads R2 intact, actually does not affect immunity to this specific bacterial model where the biologic caused 50% mortality in mice, and we have this in one of our previous slide sets that we've shared at one of our immunology days. And so not only do we have efficacy at least as good as TNF, but a potential safety differentiation and lay that on top of that, if you look at both in RA and IBD, especially TNF often lose activity over time. And part of that is likely due to -- for some reason, TNF biologics tends to have a high-level immunogenicity and being a small molecule, there's no immunogenicity to worry about. And so we could actually have better long-term efficacy with a small molecule approach than the biologic plus overlaid better safety. And plus as a small molecule, it doesn't need to be priced necessarily at biologic levels that can be price, so it's competitive versus even generics that may come into biologic because the market is so huge. We're talking about RA. We're talking about psoriasis. We're talking about IBD, for psoriatic arthritis such a huge swath of patients with TNF we don't necessarily need to price it at maybe a biologic level. So differentiation and efficacy safety plus competitive pricing we think it's a really potentially huge opportunity across a number of therapeutic areas.

Great. Okay, I'll give Naimish a break. And now Chief of Vaccines. So I guess most common question at the moment on Vaccines is the flu market. So we've obviously seen a slowdown post COVID. Just help us understand the dynamics there. Is that just vaccine fatigue going to slow down? And do you expect that to recover again?

Yes. Thanks for having me here. Yes, for those who were following 2009 pandemic, we saw that what we call the flu [indiscernible] as well. So -- and it took us 3 to 4 years to go back -- to this year, we had before. This being said, these are a couple of percentage here and there depending on [indiscernible] that is partly offset by the demographic of the population. Of course, year after year, we have more elderly in those very mature market. So that's where we are. The interest of the flu portfolio of Sanofi is the differentiated flu. This being said, our intent is to increase the value behind flu vaccination, and we are making huge progress with [ Efluelda ] in Europe. And of course, also in the international area, where we are switching from trivalent to [ quadrivalent ]. So yes, slowdown in some vaccine coverage in mature market, but increase of value through product differentiation and switch towards QIV in international areas. So that's the dynamic at play.

If you look at the split of flu sales for Sanofi, it's very big in the U.S. compared to [indiscernible]. Is that just the mix of those high dose just less adopted ex U.S.? And is that still there for big potential revenue and value driver for the flu business.

It's a very good question. So we need to step back and [indiscernible] history. So Fluzone High-Dose has been launched 2010 in the U.S. And for duration for the first few years, we've been limited by capacity. That's the vaccine story. So you basically had no Fluzone High-Dose capacity to export and to start launching outside the U.S., we are also very successful in the U.S. So we have invested, we are catching up, and now we are capital of expanding. So we launched Efluelda, which is Fluzone High-Dose in Europe 3 years ago. And we've been growing that franchise very significantly in 3 years. We are about -- if you compare to the U.S. right now, we are realizing 2/3 of their volume markets. Of course, with the difference on price Europe and in the U.S., but we're getting there when it comes to the Fluzone High-Dose market share in Europe as well. With that 10 years lead time due to capacity.

Got it. As you think ahead towards mRNA vaccines, if you're contracted with the European government, do you think that the ability to do better strain selection speed and manufacturing session will be a differentiator with European governments in particular? Or is it just a straight price negotiation with Europe?

Okay. Let me -- first, flu is super serious. Flu is a devastating disease. I think we lose sight of that. We all went through that COVID pandemic, and we saw what it was to face a respiratory disease with no infection. The value of immunization is you don't see what you prevent, right? So flu is a devastating disease. If you get flu days after that, the risk you have to get cardiovascular and pulmonary complication is extremely high. So my point is you need prevention and you need solid prevention. So what government out there, especially in Europe are asking is outcome-based proof that the investment will end up preventing flu complication because these are the flu complication that's going to yield, I would say, the budget impact, if you wish, of flu. Right? More hospitalization, more spending, direct and indirect at [indiscernible]. So the value of Efluelda is that we've demonstrated that differential outcome-based approach on the flu complications. So what matters out there is first science behind -- we talked a lot about science [indiscernible], science behind the prevention. And then yes, then safety is also very important because it's a yearly immunization. And the least we can say is that we need to improve the mRNA for generation we had on COVID. So we are also quite [indiscernible] working on that. mRNA new generation needs to be safer, and they need to be thermostable, and they need probably to offer protection that is of bigger duration. So I would say, clinical proof safety, for sure, value for money. And then you have all the pragmatic, I would say, points that are important as well. I mean they want their fridge filled as early as possible for sure. But I think there is an order in the conversation we're having with [indiscernible] there in Europe.

Got it. Okay. I'm going to move to pneumococcal vaccine. This is a question on flu. And so -- again we see in pneumococcal vaccine, the obvious gap in Sanofi's portfolio but recently published Phase II data on PCV21 and perhaps you can just explain how that's differentiated from Prevnar 20 which is clearly the dominant player in the pediatric market in pneumococcal vaccines.

I can see that time running. So let me try to do the executive somewhere here. Very excited by the Phase II data, by the way. We presented extensively on June 29. I think the progress we're making on the portfolio. So I'm sure you guys have the time to catch up. PCV21, we're adding 9N, which is one serotype that is providing 5% to 7% extra protection compared to standard of care. So we think we have a window of opportunity to differentiate that offer. We've chosen to go pediatric simply because pediatric is 80% of the served market in pneumo conjugate, 80% of this served market in '22 were the pediatric sales. And of course, because also we see synergy with our current portfolio. We are far the #1 hexavalent provider in the world. So we do promote pediatric vaccination. We have also a contractual synergy there. So we also see a value having a pneumo conjugate portfolio, completing our current offer. So yes, so exciting. We're going to start Phase III next year, and we plan to submit by '27, so that we can fill the gap in our portfolio, as we said. Yes.

You didn't mention serotype 3, but that seems to be certainly it comes up and if I pull the chart, it's a lot better on serotype 3, as far is that important?

Yes. Well, every detail will matter. So it's a Phase II, let's see what Phase III will matter. But yes, if we can have -- if you take as a parallel or may not go quite as we speak, I mean quite few, we have a superior response on C of the 4, and we know that's a differentiating factor, especially for a country doing C only. So you're right as well. There is a number of serotypes and your performance per serotype that will be looked at by regulator. So we'll see what we have in the label, but that can be another differentiation for sure.

Okay. RSV is another hot topic at the moment. So you've got two vaccines. Obviously, we've got Beyfortus [indiscernible]. Just in terms of the toddler space, there was also something on which we saw some data on at the vaccines. Can you just talk through the perceived unmet need there because I think that's where we get the most pushback on. Is there actually a market for a toddler vaccine?

Let me start by Beyfortus, to answer that question, Graham, but we are so excited to launch that first and best-in-class. You also know there's also, I mean the reduction of hospitalization by 80%. This is mind blowing. So we're getting ready to -- and so I'm sure the ACIP third recommendation that are very positive for the intervention. So we are ready to launch in [ H '23 ] both in Europe and the U.S. and very excited about it. So that will protect the infant in their first year of life on where most of the burden ease, but I'll come back on that. So Beyfortus is an important prevention tool for the production of those baby. And also, by the way, to avoid the jamming of the pediatric infrastructure. We're discussing with a lot of the European government as we speak. And if you follow the news the past 2 years has been very, very difficult. In South of Europe, in particular, when it comes to emergency reanimation, so that will help alleviate some of those overwhelming number of patients coming every year. The toddler approach is a complement. The area is the burden -- when you develop a vaccine, developed vaccine against a burden, against so that you met a need that will bring a collective benefit most often for first stage. So first year is not enough. You also need to prevent in the second year of a [indiscernible] toddler, 12 to 24 months. And we are extremely excited by the data we shared in June 29. On the kind of the efficacy that we see with [indiscernible] vaccine capable of controlling the [ second year of life ]. So in short, baby will be immunized first years with or protected with Beyfortus and then after the season, you will protect them second year of life with the vaccine. So we see a complement here to really protect the full [indiscernible] position of our infant and toddler.

And then I was going to wrap actually on Beyfortus, so obviously, you've got the -- as you referred to the impressive data on approvable ACIP in the U.S. convened ad hoc meeting to recommended. So it looks like the U.S. launch is going to be in full effect. And just perhaps give us an update on ex U.S. markets? And where do you expect to be in this season or a lot of them are going to be delayed until next year to get reimbursement?

No, we will launch in Europe as well. So I talk to you through a lot. 10 years delay. The beauty of Beyfortus is that we've been capable and of launching in Europe at the same time of the U.S. So that's -- we're very pleased about it. Of course, the U.S. will be the #1 market for us. There is no question about it. But we're having very positive conversation with both Spain and France that will certainly launch what we call public program towards all infant protection. So really trying to protect the -- most of the [ core ] in the first year of launch, which is a good signal that Europe is out of the innovation a bit quicker than in the past. So we're very good about it.

Spain and France, I knew -- or is there any option that you could see a public program in any other countries?

We'll launch in Europe. It's a European legislation, but the public conversation we're having are mainly in France and Spain, as we speak.

So for a country where you don't have a public program that would be a private market?

Yes, that would be private market on both...

Okay. And then last question on manufacturing. So big launch everywhere. And presumably the plants have been working very hard, any kind of manufacturing bottlenecks or issues or...

Less than what we've seen in vaccines. So it's a mAbs. So first, it's an alliance that we have with AstraZeneca. So AstraZeneca is the manufacturer here. But compared to our experience in vaccine, we see less bottleneck to your point, what we see on other compounds. And we took very early I would say, bets on volume available for that launch, knowing the product profile. So we will not launch everywhere to your point, but where we think we have an interest, we are gearing up so that we can meet the demand.

Great. Okay. I think we've just about on time. So yes, thanks very much Naimish and François, great to see you today, and enjoy the rest of the conference.

Thank you very much.

Thank you.