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I'm Sachin Jain here from the European team at Bank of America. My pleasure to kick off with the next company, which is Sanofi. We have Mike Quigley, Chief Scientific Officer. I think many of you may be less familiar with Mike. So I'd ask Mike to perhaps give a minute or so background on himself and then I'll get into questions. So with that, Mike, over to you. Thanks for your time.

Thanks, Sachin, for having me, and good morning, everyone. A pleasure to be here. Mike Quigley, Chief Scientific Officer, Global Head of Research at Sanofi. I joined Sanofi coming up in about 2 years ago. Remit within the organization is everything from early discovery through handoffs at Phase I both internal and external innovation. And really, I came to Sanofi 2 years ago, and I'm sure we'll get into some of this today with the goal of sustaining a high-quality output pipeline from the research organization in a way that's much more efficient and effective than has hopefully been done historically within the organization. And I think, even more important as we think about where Sanofi is going in the future, that stability and long-term output and durability thereof is going to be increasingly important.

Thank you very much. So I'll kick off big picture, and then we'll drill into some of the later stage, may be less close to and then we'll do sort of circle back to research. So I mean, the biggest picture question on everyone's mind is new CEO, new Head of R&D, what's filtering down to you as the mandate and objectives. That's a super broad question take it as you will.

I'll run with it. Belen enroll, obviously, since April. Paulo has joined us now 3 weeks ago as the Head of R&D. And I'd say starting with the CEO mandate, it's clear coming in that Belen had a purview enterprise-wide assessment around R&D, but also the group level, sort of where we are, where we should be going. Through that process, it's reaffirmed key core areas of focus going forward, I&I, rare diseases and vaccines and an ongoing effort around thinking through what additional spaces, both therapeutic areas and white spaces, if you will, that the company should move into based on our internal expertise, opportunity, strategic fit, et cetera. So that effort is underway.

You would have seen, obviously, in the context of Paulo's remit coming in with Belen now again, just 3 weeks ago. Prior to his arrival, we made some critical decisions in our late-stage pipeline, terminating amlitelimab, itepekimab and balinatunfib. What I would say is Paulo, even 3 weeks in, is already leading the effort on an additional rigorous assessment of the late-stage development portfolio, the initial focus thereof. I would imagine Paulo coming in, he's a rigorous scientist, experienced in sort of broadly global organizations, late-stage development, that will be the immediate focus as we think about not only expanding into areas as I articulated, but making critical and rigorous decisions on our current pipeline going forward.

I think the criticality of sort of where we are within the organization, you should expect for us, but even more so going forward, quicker decision-making, transparency, more of an underpromise, overdeliver mindset as we think about how we approach scientific excellence within Sanofi going forward.

Can I just touch on the parallel piece? So does that mean we should expect more, sort of pruning of Phase II, Phase III as we sort of enter the back end of this year, whether that be 3Q or full year?

What I'd say is the outcomes have not been determined. I think what we're going through and what Paulo is driving is sort of deep assessment of 2 things in particular. I mentioned scientific rigor. I think an honest assessment of where we are from a risk balance portfolio. Historically, we've been first-in-class or best-in-class driven mantra. I think what you'll go into -- in our, both the end of this year, but also in a future-looking statement, where we're much clearer about articulating what the risks are in our programs. And being measured in how we deploy capital for those programs. So whether or not there's a pruning or a reassessment of the relative capital allocation for some of these portfolio programs, I think that will play out. And obviously, we'll announce more information when it becomes available.

And then I don't know whether this is correct, but I sort of heard the pending [ Paulo ] starting sort of proof of concept or Phase III starts were all put on hold. Is that still the case? Or are you sort of still stuff flowing through?

What I would say is it's generally business as usual, key strategic decisions around Phase III starts, obviously, the capital required for those. We're not necessarily put on hold, but they certainly were given the chance for Paulo to weigh in, and that's occurring as of last week for many of our programs that net in the mid- to late-stage start. I think it's prudent as we think about any new leaders coming in. But again, back to that introduction of more rigor as we think about risk assessment and balance of our portfolio.

Okay. And then as investors are very squarely focused on what you're going to do externally to bolster pipeline, and we'll hear that in due course. But just again, organizationally, I don't know whether it fits within your area, do you get involved in that? Sort of screening of targets you involved from a team perspective, what's the mandate? Just any color there.

Yes. Happy to comment on that. I'd say from a sort of BD perspective, R&D front center, the core of everything we do in BD. I think R&D helps assess with the broader group strategy around 3 key areas: so strategic fit, obviously, scientific merit and unmet need as we think about where any particular asset would be positioned and then obviously, financial -- potential financial return on that investment. Within the deep diligence that occurs, R&D diligence comes first. So once R&D has signed off on that scientific merit, the molecules, the development path, the unmet need and making sure that we meet that TVP target value proposition in the context of that asset then comes the commercial and financial sign-off. That's been the case, will continue to be the case. And that rigor, I'd say, in relative risk assessment even being sharpened in the context of that approach.

So how much time are you now spending on BD or your organization? How much time is Paolo spending on that? And sort of what areas of you been pushed to look at early, late therapy areas, new therapy areas? Just any sort of color would be very helpful.

Happy to. Yes. So I referenced it already, the commitment from a strategic mandate perspective. So clearly, I&I vaccines, rare focus in there. It's balancing our internal portfolio where we are from an expertise perspective where we can capitalize on our footprint. Both from a commercial but working backwards from a development perspective, you can imagine that's all in scope. And there, obviously, our internal portfolio is a bit harder, for lack of a better term. So then it becomes puzzle piece fitting and what makes sense and complementary in nature. Those white space areas, I have particular increased breadth in research. We have efforts in oncology, neurology, ophthalmology. So you can start to sort of see that shape.

You ask me how much time. I'll answer in the context of what I think a healthy research and early development portfolio consists of, and that's a nominally 50-50 split of internal versus external innovation. I think there's -- we should not kid ourselves that the innovation solely occurs within our own walls, but rather use various levers we have to sample that external environment. So quite a bit of time -- of my time is spent. Paulo , obviously, not surprisingly top of mind as we're thinking about what that development pipeline bolstering could look like as he's getting into the organization.

I don't really understand how BD processes where I've been involved, but just how involved do you get in sort of even later-stage assets in doing the sort of background, preclinical validation, whatever. And is that going up as well as your typical early-stage deals?

Both. And I think the -- back to the rigor and the quality in late-stage opportunities, if you don't have a deep understanding of the mechanism and even as we think about market access, the differentiation that might go all the way back to the molecule behavior and hitting that TPP and TVP, I think all bias aside, research is actually very well positioned to really dig into those and we do currently for anything we brought in. I referenced even recent Blueprint deal as having the entire value chain on deck from a diligence perspective.

So you just give me a sense of who the key people are within Sanofi now that would be at the table on BD from early, late financial, commercial? Is that a new team? Is it the same team? How much has that changed?

Absolutely. So structurally, and I think it's because it's -- I think it's a benefit, which is why I'm starting with that. BD now sits along with M&A under the CFO. So that's close connectivity, including ventures and Sanofi capital investments. So all the various levers we have to expand our portfolio in one unit. And that doesn't mean they're not in close collaboration as always, with R&D. Actually, we've been strengthened through that sort of organizational move to make sure R&D, as I said earlier, is front and center in the context of those BD and more broad conversations.

Key people, obviously, Paulo coming in, Head of R&D, signs off from an R&D perspective, just like Francois in the financials and depending on where it sits within our GBUs up through Manuela, for instance, in specialty. So you do have some new players at the ExCom level, some same, some new. And I'd say what we've done over the last 2 years has brought in and will continue to do so, the right lens of expertise in our development TA heads. So those have largely all been new. Certainly, since I've joined the vast majority of them. And the same is true of the research organization. Many of my leaders are largely new over the last couple of years. They're bringing in that scientific rigor and expertise.

So any sense you can give of how much time that sort of BDXCo is spending on early stage stuff, which has been what Sanofi legacy has done? How much there's a renewed focus from your time and the BDXCo, I'll just frame it as that, are now screening this breadth of $15 million to, I don't know, $25 billion, $30 billion deals, I think, has been roughly referenced. So like how is that? Is there a shift and you've been given a mandate of like we need to get XYZ done by XYZ time? Just trying to get a sense of urgency and shift in focus.

Maybe twofold. One is we will never move simply because of time and sense of urgency, right? We move for the right opportunity, the right assets, strategic fit, scientific unmet need, and it makes sense financially. So that is the guiding principle regardless of any arbitrary for lack of a better word, time line. I think it's an honest assessment to say that if I were up here even a year to 18 months ago, when I first joined, the focus was squarely on bolt-on Phase I/II assets. And you would have seen that in the deal flow that we brought about.

I think fast forward where we are today, there's obviously been some headwinds, some of which we came out with Q2 in terms of terminations in our late-stage development portfolio. So I think there's a healthy balance of looking at what could complement the sort of mid- to late-stage development, not without or at the exception of any of the early stuff. So I'd say today, we're certainly phase agnostic as long as it fits both strategic sort of pillar with respect to therapeutic areas, but also the right scientific fit and the right financials for us.

But given the breadth has increased and slightly broader therapeutic focus you sort of mentioned on [indiscernible] being added. Do you have the expertise to do that? And is there any sort of particular area you're focused on initially?

That's a good question. So I'd say, I'd anchor back to the core areas in terms of initial focus. And maybe just to draw the distinction you referenced in other therapeutic areas. Those are active efforts within research. I think to varying degrees, you'll see early clinical development opportunities coming out of the internal pipeline. In the oncology, I'll reference a mid-stage PD-1 IL-15 asset, for instance, we'll have additional ones coming up in neurology. That's not a commitment per se to those therapeutic areas in earnest, but rather we will, as always, find strategic ways to assess and progress any of promising medicines as they emerge. So just to draw a distinction between my research TAs and the 3 core development TAs I referenced, I&I vaccines and rare.

That being said, in terms of areas, I think the near-term opportunity is really those that are opportunities that are adjacent to the expertise we've built, in particular, in the development and commercial organizations. So back to the rare franchises. Clearly, the expansion of that could be complementary to what we're doing internally. Same is true within the I&I diseases. Obviously, we're most prominent in the context of dupilumab, but more broadly in the dermatologic and respiratory space. I'd sort of expand that to say that, that's something we know what good looks like from a diligence perspective back to the rigor. And so those are areas that, obviously, as we constantly survey, what might be an opportunity out there.

Okay. Spend a lot of time on BD, but there's a lot of investigator. Thank you for indulging I'm going to just shift on which is slightly adjacent, but any comments you can make on how you're feeling with your [ Tarrytown ] colleagues. So anything going on? I know Belen's referenced a conversation ongoing, there's been some hurdles. Just any perspective you can give there?

Sure. Happy to. Early conversations with our partners at Regeneron in terms of the alliance and what could, should go into the alliance to maximize the opportunity there, both with them, particularly dermatology, respiratory, may be a slight opportunity to expanding gastroenterology in terms of where that Dupixent footprint resides. I'd say, a prototypical assets that could be brought in from the Sanofi portfolio in lunsekimig, obviously, TSLP IL-13 nanobody and respiratory diseases. It's not been decided that, that will enter in, but that gets the sort of flavor in the shape that would come in from the Sanofi portfolio under discussion, and we'll continue to sort of evolve those conversations and obviously, when decisions are made communicate appropriately on how best to maximize that.

Does brivekimig sit within that debate as well?

Today, brivekimig does not sit within that conversation, in particular, as we think about the evolution of TNF OX40 ligands with 2 distinct targets, and the prosecution within the Sanofi portfolio in that case in the hidradenitis suppurativa.

Okay. And then how much time are you spending due diligencing the pipeline that Regeneron has talked to? So [ super dupi, ] the extended duration assets, is that now being looked at as your perspective? Would we want those to go into the alliance? And I think there's still some confusion as to what is in or out of the alliance, particularly the IL-4 receptor debate.

Happy to expand. And again, ongoing conversations. We certainly -- I would say the team collaboration is strong with respect to our partners at Regeneron and Sanofi. We are digging into the long-acting IL-13 as we think about complementaring and maximizing the alliance. You have lunsekimig on the respiratory side, for instance, in that example around COPD and asthma. And obviously, the long-acting IL-13 monotherapy IL-13 playing out per se in the respiratory space, but obviously, would have a role in the dermatology space.

So you can start to think about or see how we might shape, again, all ongoing active negotiations but how we might shape the complementarity of those 2 assets, for example in that. And there's continuing, whether it's the super dupi or anything else that they might have, we're ongoing in terms of conversations.

Could you clarify for me then where -- I mean is it still uncertain whether IL-4 receptor is in or out of the alliance? I know you say it's in, they say it's out. shouldn't be that complicated. I just -- is that sort of topic of conversation?

It's all related to the ongoing negotiations and clarifications, I guess, more appropriately. What I would say from our perspective is what makes the most sense scientifically. We know the type 2 access is incredibly important in type 2 driven diseases and respiratory and dermatology. And so for us, that's how we're framing maximizing that allowance and the types of assets that would be brought into it or could be brought in to it.

Okay. That's very clear. And then the last question, is the discussion with your colleagues advanced enough yet to be collaboratively investigating external assets?

Certainly in scope.

Absolutely.

Yes. I think the internal ones obviously have more data at hand from either side to be able to dig into, but there's always a possibility to bring in external assets into the collaboration.

So can I just check the timing of that? So the assumption has been that you probably need to fix the collaboration before you do something externally, but it sounds like they're sort of parallel tracks and it could all happen together. Is that fair or incorrect?

I think first things first is understanding in context of negotiations, the current assets at hand. At the same time, I think it's prudent to understand what else could be brought in to maximize that alliance, both from a development perspective but also a commercial innovation perspective. I would just frame that respiratory dermatology and a bit of gastroenterology in terms of what might be in scope and makes the most sense as we shape that collective portfolio.

Okay. So I was going to ask this. So gastro, I hadn't really appreciated. Could you just touch on that?

Just the EoE indication.

That's okay, fine. Okay. Sorry, one question on the side there, feel free.

Okay. I just have a question. Several years ago, you acquired Translate Bio, which is mRNA technology. You have a vaccine franchise, strong franchise. Why don't you launch neoantigens individualized vaccine using mRNA in oncology?

Certainly, I would broaden it back to your question, translate. We're making use quite effectively of that platform broadly within the vaccines, pharma collaboration internally at Sanofi. I'll reference and you'll see it emerge in our early clinical development pipeline in vivo CAR T efforts using that platform combined with some other lipid nanoparticle platforms that we brought in, and as well as our nanobody technology. So that's an example where we're maximizing that in the context of that pharma vaccine design.

I think in the recent data, as we think about early-stage, Stage I, Stage II cancers where a vaccine with a combination of checkpoint could make sense. I think that context and example is under a broader discussion that I referenced earlier as we think about what the right therapeutic area, in particular, in development and the commitment makes sense for Sanofi going forward. But it's not lost on us, in particular, the PD-1 IL-15 assets that we have in Phase II could be complementary. So those discussions are active and ongoing. And obviously, we'll communicate when we make decisions.

Anymore? This might be a question more for Thomas. But one other question I get is, should we be expecting an update on these -- on the strategy by year-end? There's been a debate of is there a CMD, is there not a CMD? Where is the current thought process?

Maybe Thomas can complement. I think we're committed to an evolving communication as we make strategic decisions and prioritizations as opposed to a single snapshot in time. I think it's on us to make sure we communicate. I'd point to Q3 earnings in October as the next opportunity to give an update on the decisions we made, and sort of future-looking ambitions for the organization.

Okay. I think -- so that's similar to what we sort of saw in 1Q, Q2, where we sort of saw a couple of slides here. This is the evolution of thought process. We should expect something similar 3Q rather than a big flash event which has had mixed success with peers in recent days.

Perfect. All right. I'm going to move on to perhaps an area of your -- closer to your expertise. So just interested as to in your 2 years that you've -- 18 months, you've been, what have you changed? And where do you think you are on the journey of improving the early-stage research and asset flow into development?

Yes, happy to. Maybe a couple of reflections, and I think it should be consistent with what I've articulated in a go-forward fashion. Sanofi over the last 8 or 9 years as I came in and sort of looked at the data set, it won't be a surprise to any of you, have had a lot of leadership changes, in particular, R&D, heads of R&D. And with that comes a necessarily reassessment of the strategy. The knock-on effect that has in the context of the cycle times that I operate under. So anything I start today in research doesn't show up to the clinic for an average 4-plus years. The cycle time and a success scenario of anything we start shows up on the market in 14 years.

So the knock-on effect of those heads of R&D and head of strategy changes have a significant impact on the perceived productivity of a research organization. So my goal over the last 2 years is actually to create a more resilient research organization with the ultimate goal of sustained high-quality output over time. You will have seen in our Phase I pipeline, a significant gap. The first in-human starts over the last couple of years have been quite honestly, abysmal, and then 1 out of 3. You'll start to see that build back and that's -- we've done some things internally. We've set up some collaborations and accelerated those starting this year in 2026, from a first in-human start and continuing on '27 and '28. That will be the first proof points. Quality of those decisions and productivity is always a lagging indicator. So you'll bear with me as we come through Phase II transitions with the rigor that we already discussed.

And the last thing I'd say is, historically, Sanofi, to an extent, has been good at partnerships, particularly in the development stage assets. But from a research perspective, has had more of a non-invented tier status, right? We brought in Ablynx and platforms and those have proven fruit. But I've moved the organization to being much more nimble and making sure we can source effectively external innovation. And you'll start to see more of that in terms of announced partnerships coming up that are more platform-size deals, meaning larger portions of a portfolio that make a lot of sense to prosecute with a partner, for instance. So more to come what I think that's been my focus.

The last thing I'll say is decision-making, whether it's AI-enabled or just frank decision-making is probably where the most value gets destroyed in the research and early development space. So that's been a big focus of ours and how we view our pipeline and how we make decisions. There's rigor included, but there's also timeliness of decisions and opportunity cost and dynamic capital allocation components of all of that, that we've looked to significantly strengthen over the last 2 years.

Within the context, going back to BD, is there a review from who's coming in that, yes, there's been a progression, but we actually need to bolster the R&D platform. Whatever may we look at is not only the assets commercial, but also coming with a research platform.

In some cases, that is a lens depending on the opportunities we're looking at. Independently with that same movement that we already referenced with respect to BD and M&A, our ventures arm and additional capital leverage that we have to bolster maybe early riskier stage investments are something that we've strengthened from a strategic lens perspective.

So we've had the corporate venture arm. I think that's a real asset within Sanofi. Others have it as well, but making sure we can understand areas of emerging biology that might not be ripe today, of course, and therefore, we shouldn't sort of take on internally, but a thoughtful risk assessment and in that case, investment for the longer term. So we're doing both at the same time. So it's a bit of everything, everywhere all at once. But I think important to land that in a way that has an eye to future sustained output on a quality organization.

Okay. I might move to the last -- just some asset question, which is probably less close, but if perhaps you can touch on that. So I'm going to start with a really big picture question. You mentioned lunsekimig, I sort of mentioned brivekimig. One of the questions I get , is it clear from the data we've seen, the bispecific mechanism is adding anything to single. So one of the questions I get is brivekimig HS data looks like the TNF. The lunsekimig data, we've just seen ERS doesn't look that different to the TEZSPIRE data. How would you contest that if you're debating lunsekimig with the context of the alliance, there must be a view that it's differentiated, I guess. So just big picture.

Sure, let's talk with lunsekimig and the Phase IIb data, where to look at it and what Phase II could look like from that potential perspective. So in that all-comer population will come back to the population versus the ITT that could roll into a Phase III statistically significant achievement of endpoints associated with exacerbation in FEV1. I think in that context, because necessarily the Phase IIb data set or patient population was broad, so 1 plus or more exacerbations, only 40% of those patients had high eosinophils. When you start in a predefined subset basis start to look more at the ITT population, call it, 2 more exacerbations, for instance. You start to see more significantly meaningful improvement on those endpoints and our Herald modeling would suggest that we should expect significant improvement across all 3 registrational endpoints in the context of the Phase III.

So it's the data set we have at hand and projecting forward in the context of that Phase III. And in particular, the efficacy differentiation. I'd say equally importantly, as we think about where IL-13 biology, we think is playing a role in the context of asthma is small airway remodeling and mucus plugging. And I would point to the PROs where we think we see a significant improvement over standard of care that might be manifesting with that IL-13 biology will show up. And so that's the sort of aggregate data that we have, and confidence around why it's the TSLP and IL-13 combination that might be lending itself and the relative regulatory end points were associated with that in a projected Phase III approach.

So just to summarize, if we looked at the data in the correct subpopulation, you do think it's showing cross-trial superiority to TEZSPIRE on excess patients and some of the PROs?

So it's tough to do cross trial as always, of course. And we looked at 48 weeks, the [indiscernible] study at 52 weeks. Obviously, Dupi at 12 weeks with FEV, so it's different endpoints. So I would cautioned against as always, the cross-trial comparison. But I think we're confident, again, in that all-comers population, the data we saw there and then the prespecified subpopulation that would look closer to that Phase III population.

And then similar question on HS, and we got the, I guess, Phase IIb coming next year.

Correct. And that obviously, that will be the data that we use to make the decision around the [indiscernible] Phase III. I think from the Phase IIa data, the placebo-controlled HiSCR50 going to 90, in the 30% to sort of 23% range, placebo-controlled. I think, gives us confidence in the context of, in that case, severe to moderate or moderate to severe patients, biologically naive.

I think that will bear out if that continues in the Phase IIb. I think for us, the contribution of components of OX40-Ligand and durability, sustainability of T cell subset inhibition beyond just TNF sort of cytokine inhibition seems to be playing out the data will tell us in the context of the IIb.

So just for the IIb, you just what target profile would you need relative to what's becoming a branded based, [indiscernible] Phase II for not only the IL-17s, but we've got the TL1A s, potentially there. You've got an asset there. BTKs will see what they show. So just like what would you need to see?

I mean there's still an efficacy ceiling in the context of the high scores. I look at HiSCR and I'd look at tunnels and really where the unmet need is going within hidradenitis suppurativa. So -- and that's what we'll be looking in the context of the IIb and making the call on to your point, differentiation what that means for patients downstream.

Okay. Can I shift to perhaps some of the Phase III assets? I know it's a bit less in your purview, but as an organization, you want to put it this way, investors basically, I think, have given up on the Phase III reads next year, whether that be frexa, or [indiscernible] or PCV. So actually just a couple of hits on each as to whether you still believe why? And I think in the case of frexa there's been some changes in trial design or endpoints.

So maybe we'll start there. So with frexa ongoing conversations globally with regulators to adjust the primary readout from superiority and non-inferiority. The --

but still ARR?

Still ARR as a primary. And the rationale there is with an active teriflumide sort of comparator with even with a superiority hypothesis that activity sort of makes it difficult to power. And so that's the rationale for the conversation. Equally importantly is the key secondary endpoint, which is disability progression. So I would say from a Sanofi lens, that's -- those are the 2 data points, in particular, the disability progression that we're using to judge the potential for frexalimab and RMS going forward. And I think that's the key aspect.

Why is that important? Frexa is a nondepleting CD40 ligand antibody covers both adaptive immunity inhibition thereof driving a lot of those acute inflammatory aspects of the disease. The chronic smoldering inflammation driving presumably in large part, more disability progression is more innate in nature. Frexa also inhibits that access. So mechanistically, that's the reason why we're making sure that both the primary ARR as well as disability progression of 6 months equally important as we wait the promise of that drug.

So can I just check because I don't spend a lot of time on this. So the target profile relative to CD20, we've seen on BTK, we'll see the second shortly. Is ARR comparable to CD20s and better progression? Is that the target profile?

Correct.

And so can you just run over in Phase II, what gives you the confidence in that? Because some of the stuff we get back is this MRI data is super hard to extrapolate to one or both of those end points.

I think that's the data we have at hand to sort of assess the disability progression. And obviously, we're bolstered by the approach that we took with tolebrutinib capitalizing on that in the context of disability progression. So that's data at hand, but the 6-month disability progression data set in the context of the ongoing study will be important for us.

So how much better than CD20 do you think you need to be? So CD20 are sort of -- I think kesimpta has a study versus a [ badger, ] which is like 34%. Do you have in mind the target profile or have you disclosed how the study is powered for what sort of CDP you're looking for?

We've not disclosed that.

But you have -- is there a target profile?

I think the critical would be, you need to at least meet that bar from an ARR perspective. And the benefit would be disability progression to patients.

Okay. And then could you touch on infection risk? Because I think the non-CD20 mechanism of having better infection, which was also a putative advantage, but the Phase II had elevated infection.

I think we'll continue to play out with more sort of patient years in terms of the infection risk where that really looks different from a CD20. Obviously, that's part of the TPP and how we think about it.

So on a scale of 0 to 10, and investors are like 1 or 2, where are you on the excitement scale of frexa with the organization like you?

I think we have no favorite children on the scale of 1 to 10 No. I think it's -- look, back to the rigor in all honesty. I think we'll see the data at hand, and we'll make a call on frexa both in RMS, SPMS, obviously, the following year, but more broadly, including in transplant and the efforts we have with frexalimab.

Okay. If I move on to riliprubart, one failed study has driven investors to sort of much more cautious on the second. They are different settings. That's critical. One could argue different biology, but I'm just interested in your thoughts.

Absolutely. So maybe including the conversation we had in Q2, but I'll just carry on from that. So IDMC obviously reviewed importantly, both MOBILIZE and VITALIZE. To your point, MOBILIZE, a much more difficult-to-treat patient population, more heterogeneous, obviously, refractory IVIg starts in that case, the IDMC recommended not on safety. No safety findings, but on futility, unlikely to meet the primary endpoint from an efficacy perspective.

At the same time, they also reviewed both safety and efficacy of the VITALIZE study and recommended progressing forward. So that's point one. we're still on track to read out in 2027. As we think about the VITALIZE study, these are now a more homogeneous patient population, dependent on IVIg, 70% of those patients upon withdrawal will progress. And so this now biologically and from a patient population perspective, I don't know that, that gives us confidence, but at least that the IDMC sort of assessment could told us to go.

Can you just touch on what the IDMC looks at when that second study having stopped the first? Is it futility look, is it a no harm look? Is it -- this is going to get placed to what our putative profile is? I'm not quite sure how the IDMC process works.

It's really the safety, first and foremost from a know-how. And then subsequent to that, do futility analysis in that order.

Okay. And the timing of that data is?

2027.

Okay. If I then moved on to -- actually, I didn't miss this initially, but efdor, where you've had the Phase II data that was presented at a conference recently. Regulatory debates ongoing. My sense has been some sort of safety hurdle if you have enough safety data to an accelerated file or not. Anyway, long-winded question, but like where are you with the regulatory aspects of an accelerated file?

Yes. So with efdoralprin alfa, obviously, the Q3 week regimen hit all primary secondary end points in the context of that study compared to the Q4 week and then plasma-derived AAT. So we are progressing with regulatory conversations with the assumption of accelerated approval and the assumption that we'll continue to track to the end of this year from a filing perspective. I think from the overall structure, that data would obviously be AAT level -- sustained AAT levels compared to the Q weekly plasma derived standard of care.

From our perspective, importantly, the open-label extension rollover from that ELEVATE study, the Phase II study that we presented continues to generate safety data and efficacy data that will complement that conversation.

And of course, we'll have a Phase III study that will be dependent on the accelerated approval or be required under the accelerated approval, if granted, and obviously for European filings. So all of that underway as we speak.

So I might have missed this, but there isn't -- I thought the conversation was we're going to see how the regulatory conversation goes and update back end of the year. But if basically what you're saying, it sounds like it's more advanced that you you're comfortable enough to have that filing go in at the end of the year? Did I get that right?

That we still need to have -- we're having the conversation. So just -- I guess what I'm articulating is we're on track as we've communicated in the context of that conversation from the potential for an accelerated approval as well as what I referenced was just the open-label extension, adding additional safety to your earlier part of your question and efficacy, of course.

And is the gating factor correlation of the biomarker to endpoint or as a gating factor safety?

There's been no safety findings to date in the context of the Phase II. It's really the correlation between biomarkers and clinical outcome and improvement.

And again, I'm not as close to, but Europe and U.S. regulators seem to have had a different view on that historically. Is that still the case?

Correct. That's why the Phase III study will be required for a European filing.

And then I've had a number of questions on safety. So from the detailed data, there was an imbalance in discontinuations and adverse events. So perspective there?

So for efdora, no significant permanent discontinuations based on adverse events. We did have some transient antidrug antibodies, only 2 refinery nonneutralizing in 2 patients in the context of the study. So not material difference in the context of permanent discontinuations on efdora compared to the Q weekly plasma drive to AAT.

Okay. So no real safety debate. Okay. So I've been through the list of pipeline assets, I get asked about just what else would you have us focus on?

I think early days, maybe a few in particular, early days for the STAT6 programs. Obviously, those 2 are in partnership. We have 2 in the clinic now, an SH2 domain inhibitor with our partners at Recludix and a degrader with our partners at Nurix. Maybe I'd highlight upcoming ESMO data for our PD-1 IL-15 asset in solid tumors, colorectal and lung, the furthest along is colorectal data. We will be presenting that data at ESMO.

In particular, I'd point to CRC stratified with and without liver mets as potentially interesting in the context of there. And then I referenced maybe some other therapeutic areas earlier. We have 2 gene therapy programs in ophthalmology. We have a program that's in Phase II in neovascular AMD. And then a second gene therapy program also moving into Phase II in geographic atrophy, targeting 2 key nodes of the complement pathway as we think about that disease.

Okay. And that's the first asset you mentioned, I had on my list. Are we expecting data for the STAT6 at some point by year-end or early next year?

Both early programs. So we have not guided to any material data release between now and 2028, which is how far we project out. Both Phase I assets will continue to present themselves as they emerge.

So no data for either the foreseeable future?

Not today, but we'll obviously update as that data becomes available.

And are those assets -- just again, apologies for the question, where do those assets sit relative to the collaboration?

So currently, our partner Recludix is responsible for the early clinical development, we are responsible for the degrader development to clinical development that is.

I think we're just on time. Are there any questions in the room before I wrap the session? Okay. Mike, thank you so much. Very helpful. Thank you.

Okay. Perfect. So good afternoon, everyone. Thank you for joining this session at the Sanofi fireside chat. For those of you who don't know me, I'm Sarita, European pharma analyst at Morgan Stanley. And I'm very pleased to have Manuela with us today, Head of Specialty Care at Sanofi. Thank you so much for joining us.

Thank you very much for having me.

Thank you. So before we get started, just some housekeeping. So please note that this presentation is for Morgan Stanley institutional clients and employees. For all important disclosures, please see the Morgan Stanley disclosure website.

Okay. With that, so perhaps we can start off kind of more high level. You stepped into the role before the change in the CEO. There's been lots of things in terms of pipeline review, strategy changes. So what are the major changes you've observed now as your time in the seat? And perhaps what is it in the specialty care business that you've changed your mind on where have been, kind of, key areas of strength, things that are perhaps not as good as you wanted them to be moving forward?

No, thank you, Sarita. And very happy to be here. I think overall, when I think about Sanofi in general, we have 2 objectives. On the one hand, we want to make sure that we continue the great performance that we currently have on the business going forward for the remainder of the decade and a big part of that is driven by Specialty Care. So strong commercial performance.

We're one of the fastest-growing companies in the industry at the moment and continuing that growth, both on Dupixent and as well as on the rest of our portfolio is really, really important. And the second priority is to think about how do we sustain the momentum into the next decade, especially with the Dupixent LOE and making sure that we can -- yes, continue that growth trajectory in the future as well. And those are the 2 things that we're working on. I think in general, when I think about addressing those, and we've talked a lot about in the individual meetings here about BD and M&A, that is a big part of our focus at the moment.

We're also looking at how do we increase our R&D productivity after some of the setbacks that we've had. We have a new R&D head that just came in, Paulo Fontoura, who is very excited about working together with us. And I'm very excited to collaborate with him on these opportunities going forward. So those are the key things that we're working on.

We are going through a strategic review with the executive committee to really look at the strategic areas that we want to focus on. We've already made decisions to say, immunology continues to be a core area of focus, rare diseases will be a core area of focus as well as vaccines. But we're also doing an enterprise strategy review to say, do we stick with those 3, do we expand into a fourth? What would that fourth look like? That's ongoing work. We want to be very disciplined and intentional about those choices, and we'll make that decision in the coming months.

Perfect. And you touched on BD M&A focus. Previously, perhaps the focus was more towards Phase I, Phase II assets, now emphasis has shifted more towards a late-stage commercial deal. So perhaps you can outline the priorities for BD M&A moving forward. Are we looking to fill '28 to '31 revenues post '31 revenues when Dupixent goes LOE?

Yes. So I think our priorities from a BD and M&A perspective, first of all, the criteria that we use haven't changed. And I would say we're still looking at early-stage assets but we are now combining them with a focus on later-stage deals, also commercial deals. And the criteria we are using is always to say, is it great science? And is it a strategic fit for us? I just mentioned the 3 core therapeutic areas that we're focused on. And within those areas, looking at opportunities for bringing new science into the fold. Is it differentiated? Is it addressing an unmet need? And then does it make financial sense for us? So yes, we have pivoted slightly more towards commercial and late-stage deals. But as I said, if there's exciting early-stage science that we're interested in, we will also go after that.

Perfect. And I think previously, Sanofi spoke to EUR 15 billion for early-stage deals, EUR 20 billion to EUR 25 billion for later-stage deals. Is that still the right framework? Or is there potential to go above that?

So these numbers were based on maintaining our current credit rating. We -- I'm not going to reiterate the numbers because we're having discussions. We are -- we have a very strong balance sheet at the moment. We're also generating more cash flow as we speak. I said earlier that we're one of the fastest-growing companies from a performance perspective as we speak.

And that, of course, helps us to generate more cash to potentially do bigger deals, whether that is 1 deal or multiple smaller to medium-sized deals, all of that is possible. We're not specifically looking at a particular size or a particular opportunity, but we are looking broadly at these things, yes.

Sure. And just a follow-up on that. So should we think about it as a string of pearls or is one transformative deal on the table?

I think both of it is possible. We are looking at larger deals. We are looking at more small- to medium-sized deals and a combination of those again, based on the same criteria, as I mentioned earlier, is it part of an area that we're strategically interested in? Does it make financial sense, especially when you think about that Dupixent LOE and the earlier part of the next decade. Does it help us address that part of the equation? And then does it make financial sense? We want to be disciplined around those things.

And you touched on the discipline -- and the financial backdrop for BD, I mean, it's tougher. There's a lot of large cap pharma companies looking for assets. So how are you kind of weighing the competition for good assets? And then also, do you think that your BD process is fast enough, particularly given you've just had the new Head of R&D joining the seat, are you ready to move quickly?

Yes. So I think there's definitely -- first of all, with the new executive committee being a smaller team, more focused, more nimble, and Belen has the ambition to really create this 1 team dynamic where we work together in a collective fashion on things. We have been looking at opportunities. Paulo has hit the ground running. Literally speaking, he knows some of the spaces that we're playing in really well. So we're not going to lose time because of that, for sure.

And the other thing that I would say is that the connection with the Board, which is an important part of us being able to move fast is also something that we're investing in, and we're focused on. And I think if the moment is right, the space has always been competitive, right? That hasn't changed. It continues to be competitive. But if the moment is right and if the right opportunity comes around, we will be able to move fast enough.

But again, I will just add something, diligence matters, right? So we're not going to compromise on diligence. We want to move fast, but at the same time, we want to make sure that we do it in the right way.

Perfect. And how should we think about China as a source of innovation. I think Sanofi has previously spoken to in-licensing from China. So will this be within your, kind of, key therapeutic areas that you touched on? Or would you look to China for selective oncology assets, for example?

Yes. So the way I look at China, we look at China is in 2 ways. China is a large commercial market where we have both launched global assets. Dupixent has launched in China. Sarclisa has been launched in China very successfully. Both of those brands are growing. We've recently launched Qfitlia in China as well. But we've also looked and gone after local opportunities that are truly a local opportunity for the China market and sometimes outside of our global core areas of strategic focus cardiology, for example.

So if the opportunity is right, and there is enough -- I mean, given the size of the population, there's enough local market opportunity, we will play with a local asset. So that's the commercial opportunity in China. The one thing that I would always look at from a China perspective is the value of the innovation recognized because, yes, there's a lot of volume in the Chinese market but sometimes prices can be really tough. So that is always something that we weigh whenever we make decisions for China-for-China plays.

The other thing is, China innovation for global. We have an R&D team in China and the opportunity to really accelerate innovation, global innovation, thanks to the China footprint and potentially also looking at partnerships is definitely something that we're interested in, yes.

Perfect. And then I suppose when you mentioned you're evaluating what the fourth therapeutic area could be. Sanofi, of course, operates in neurology, ophthalmology, oncology. Paulo's background is perhaps more neurology weighted, how should we think about what the front runner is for the fourth opportunity?

Yes. And I'll go back to what I mentioned earlier, we're doing a -- we call it enterprise strategy assessment at the moment, where we're really taking a very intentional look at all of those opportunity areas, both the ones that we currently are playing in or have pipeline assets in, but also white space opportunities that may go beyond that, and the intentional focus on, is there enough science in those spaces? Do we have the right capabilities and better capabilities than other players do in the space or can we build them in time with the right investment focus. And if we go there, what are we going to have to give up somewhere else in order to play from a capital allocation and portfolio perspective, the discipline and investing where we can actually win. So I'm not going to say it's going to be this area versus another. Too early to tell, but we are going to make that decision in the next couple of months.

Okay. Great. Looking forward to that. Perhaps we can switch to the Regeneron collaboration, which I'm sure you've been asked about multiple times today. Belen said that you're focused on rebuilding trust with Regeneron, the litigation is still ongoing. And I appreciate we can't get into the specifics of the case, but perhaps you can kind of give us an update as to where we are with the litigation? Is this a precondition, are you resolving it for the relationship to move forward? Or can we work around or you work around the litigation?

So when I think about the litigation, that's a very narrow area [ that is ] focused on, and it's in early stages. To your point, I can't comment much on it. But I've been working with Regeneron for the last 6 years. First in my regional role in Europe very closely at the local level and as the region head. And then the last 3 years, I was responsible for Dupixent globally and for the alliance globally, and I've worked with Regeneron on all kinds of topics.

And I can tell you that the operational ways of working between both companies are really strong. We've always worked strongly together. And the litigation part of it, we keep that completely separate, right? Because both companies have 1 goal to maximize the opportunity behind Dupixent and to try and be successful collectively as a team. So I really look at those things differently. Yes, there is -- there are discussions going on, both at the CEO level as well as at the team level to say, is there a potential to expand the alliance and how would that look like? And I think there's a willingness on both sides to look at that. We are still in active conversations.

So I don't have more to share with you at this point in time. But I think there's an interest on -- in both companies to really say, we've built something really amazing with Dupixent, and it's been a lot of hard work. We have really strong capabilities, we've built strong relationships. We have -- we have great teams, especially the customer-facing teams and an opportunity potentially for follow-on assets in the alliance that could make a lot of sense, and that's what we're currently discussing and working on.

Perfect. And you touched on bringing additional assets into the alliance on both sides. So which assets would Sanofi like to bring to the alliance, and which would you like Regeneron to put in? And how are the discussions progressing? Can we expect an update here, kind of, before the end of the year?

So I'm not going to comment on either of those 2 questions, unfortunately. So we're looking at different assets to say, do they make sense in the alliance how do they fit with Dupixent life cycle management, the LOE in 2031, which is the earliest time frame as I'm sure you all know, and given our strong patent portfolio that we expect potentially the LOE, we are hoping that we will get a few more years, and we feel pretty confident we're not going to put a time line to it. It's way too premature because we haven't been challenged on our compound of matter of patent as we speak. But there are some assets that we're discussing that could really fit well from a follow-on perspective where we could leverage the existing infrastructure that we have collectively built. We could leverage some of our capabilities as well as the rebates that we have to, accelerate a future asset in the alliance potentially.

And to the extent which you can answer, Regeneron have been perhaps more public with saying they'd like to rethink the economics of the alliance, maybe into ex U.S. geographies. How does Sanofi think about the economics of the current alliance?

I think at the end of the day, it has to -- it has to work for both parties, what is absolutely true is that, when the deal was done, the original deal was done, both companies were in a very different space in terms of their ability to contribute capabilities and to work together, and we're taking that into account. But at the same time, we want to make sure that it's a win-win for both sides. And that's what we're working on, and we're making progress.

Okay. Amazing. And when you think about immunology and it's 1 of your core therapeutic areas as you've outlined, how do you weigh whether an asset fits better in the alliance in terms of buying something together with Regeneron, for example, or, kind of, going at it alone?

So for me, the alliance point is never the starting point. The starting point is always is, is there a strategic opportunity, and it's there exciting science behind an asset firstly. And then the question is, does that fit best in the alliance? Or does it fit best in a nonalliance play. So that's the way we are evaluating opportunities. And there are opportunities that we're considering in a nonalliance context.

And there might be other opportunities, especially in areas where Dupixent already plays, dermatology, respiratory in some of those spaces where we would say, yes, it makes sense in the alliance, but it's never the starting point, and I don't think it should be the starting point. For me, that's a how-to-play question rather than, is it amazing science? Is it an opportunity for us to address an unmet need in a patient population that's currently not being addressed. That's always the starting point.

That's very clear. And perhaps we can move on to Dupixent. You recently raised the guidance to EUR 25 billion of sales by 2030. So help us understand, kind of, where we are on the different indications in terms of what's driving that incremental growth in confidence? Is it a particular disease? Is it geographic expansion? Maybe both, help us frame the building blocks?

Yes. I mean we're really excited about the continued growth of Dupixent. We are growing for the first half of this year, north of 30% as you've seen. We've had our first EUR 5 billion quarter for Dupixent. And it's really driven by all of what you just said, it's existing indications. Atopic dermatitis, for example, which is the first indication that we launched in, we have a 20% bio penetration in atopic dermatitis in spaces like COPD you have a single-digit bio penetration.

And the same is true across all of the different indications, very low biopenetration rate, even asthma, which is a space that was quite mature when we entered it. Even there, you're talking about 30% bio penetration. So there's a lot of room for growth and opportunity because it means a 20% biopen means that out of 10 uncontrolled patients, 8 that should be on a biologic are not yet on a biologic.

So there's a lot of opportunity still to grow that space. And then you think about -- because a lot of these biopen numbers that we are referencing are adult population numbers. But when you look at pediatric population, you're talking about much lower biopenetration rates, even though atopic march is real, right? This is one of the areas that we are looking into from a data generation perspective to say, if you treat earlier, can you avoid kids triggering comorbidities basically for children that start with AD, but then potentially develop allergies or potentially develop asthma, other comorbidities. So there's a lot of opportunity for growth in younger groups -- younger patient groups.

You mentioned geographic expansion as well. And then again, depending on the indication, we're in different life cycles, some of the indications we've just recently -- indications we've just recently launched. Others have been around for a while. And then competition helps, right? It's -- we've always said, with more players coming into fairly immature market spaces and atopic dermatitis is still a very immature market space. COPD is a very immature market space. It helps create the awareness and the education that advanced treatments are available, and it just helps rise all boats. So that's how I think about the opportunity. We feel confident about the EUR 25 billion ambition by 2030, and even though when we think about the next couple of years, some of that growth will slow down, right, because you are anniversarying a year where we've also had some GTN upsides.

We've talked a little bit about that during the Q2 earnings call. And once you have such a large base, that you've created, it is harder and harder to show growth rates of 20% to 30%. But this year, we're still able to deliver that, and we're very excited about that.

Amazing, and you touched on COPD and maybe somewhat preempted where I was going. But it's in the relatively, kind of, nascent stage in terms of market formation. We do have a competitor that just posted very strong data in the eosinophil over 300, where Dupixent play, how are you viewing competition from IL-33?

So I think, as I already mentioned, I think tozorakimab data is strong data. And given the space, the COPD space being so nascent, I really believe it requires more players to help educate both pulmonologists but also patients that there are more treatment options out there for them and that an add-on therapy to what they're currently using is really important. I would encourage everybody to look at not just exacerbation reduction in that space but also look at lung function improvement and quality of life data. We've seen that, especially in the case of Dupixent, where patients especially the lung function improvement that's actually something that they can feel in their everyday life.

For example, 1 of the patients that was treated with Dupixent was -- couldn't actually dress himself anymore. His wife had to dress him because the COPD was so severe after having been on Dupixent for a few months, he was able to dress himself again. So these are the small improvements that might not matter for us that don't suffer from that disease but a really meaningful improvement. And you tend to see that more when you have lung function improvement and you have quality of life improvement. But I really hope that with more options available now in the COPD space, that we can get more biologics usage overall.

Amazing. And you also touched on Q2 having perhaps a nonrecurring gross-to-net component but also recurring -- of which 340B is a component. So how should we think about the 340B benefit moving forward to the extent you can quantify, that would be useful. And then separately, when thinking about 340B and the legislative changes, how impacted is Sanofi by this?

Yes. So I think Q2 and in general for the first half of this year, the vast majority of the growth is driven by demand, and we expect that to continue. And then there was, to your point, there was a recurring GTN component that was driven not only by 340B, but also by operational efficiencies in general, we always think about how do we improve our go-to-market model and how do we drive efficiencies overall in our business. Part of that was 340B.

And while we are aligned with the core principles of the 340B program. There's quite a bit of abuse going on with that program. So we welcome the current discussions. They're still ongoing. It's too premature to say where they will lead but it's definitely helped us to really say, how do we get more control around 340B. We call it 340B scrubbing that we've successfully done. Again, one of the elements that has driven the operational efficiencies and some of that will be recurring, but some of the GTN benefits that we saw in Q2, in particular, was a one-off effect of some accrual releases from prior periods.

So -- and that, of course, won't recur. And then just a plug for 2027 as we anniversary some of the GTN benefits from this year, you won't, of course, see that happening again because you reach a moment especially from a 340B benefit perspective where you can't do more. So I don't expect that to increase significantly over time.

Okay. Very clear. And Sanofi have outlined kind of multiple life cycle management opportunities for Dupixent and whether it be Q4 weekly high dose co-formulation, how should we think about the strategy here? Is this to strengthen IP? Or is it they can be commercially meaningful? And if so, are these upside to the EUR 25 billion target?

It's all included in the EUR 25 billion target, even though like we definitely look at those as opportunities to help drive better patient satisfaction. And there are 2 elements to it. There is a 600-milligram asthma opportunity that we are pursuing, which is specific for asthma, Q4W. And then there is the co-formulation with hyaluronidase that we had talked about in our Q1 earnings call, which is also a Q4W dosing opportunity, and I'm thinking about it more from a -- how can we deliver better experiences for patients in general.

That was always part of our strategy to think about how do we provide more convenience in general for Dupixent. IP, we will always strive to protect it with IP, but it's much more of a patient opportunity play than an IP play, at least for me personally.

Okay. And we're seeing longer acting kind of competitors pursue the AD market, particularly Apogee, AbbVie, for example. So how should we think about some of these longer acting players as we move forward? Is your own Q4 weekly enough of the defense?

I don't -- yes, I don't see it as a defense. First of all, I think when you think about longer-acting drugs, for me, the first thing that any player needs to -- or any asset needs to hit is efficacy and safety, right? Because if you don't have a proper efficacy profile that can compete with the standard of care, and that is true in any of the indications, you need to be good at relieving itch and skin clearance in atopic dermatitis. And as we talked about in COPD, it's not just about exacerbation reduction, it's about function improvement, and it is about quality of life.

So first of all, you need to hit on efficacy properly. And then safety, and I think that's where Dupixent really has just years of safety data that is unmatched in 1.5 million -- more than 1.5 million patients on therapy today but many more patients that we have treated over the years, that matters. It matters especially to dermatologists, but also to many other specialties that we work with. And then to your point, if there's a long-acting opportunity on top of that, that's great. A lot of these programs are in earlier stages, right? We have not seen Phase III pivotal data yet. So that will hopefully come.

And then I really believe that there is opportunities for more players to play in the current context, given what I said earlier about biopenetration rates, et cetera. So let's see where the data goes and how they read out and then we'll be able to talk more about those.

Very clear. And taking a step back, Sanofi have also outlined our EUR 10 billion sales target for your pharma new launches. What are the 1 or 2 assets within this portfolio where you see kind of the biggest upside or you are most excited about versus Street expectations.

I think the -- I'll mention 3 because I feel there's a diverse set of assets that is included there. So on the 1 hand, Ayvakit, from the Blueprint acquisition in systemic mastocytosis. It's a really important drug that is addressing a real unmet need in a space that is underserved today. And there are many patients who are diagnosed on systemic mastocytosis, but they are not yet on the appropriate therapy.

So our ability to put our rare disease capabilities behind Ayvakit and working together with our rare disease teams, especially the customer-facing teams also the knowledge that we have when it comes to, how do you work with advocacy groups, how do you find patients, how do you diagnose them, how do you convert them on therapy, and how do you keep them on therapy, all of these things will really help us continue the growth trajectory and the patient uptake on Ayvakit that we're currently enjoying and there's a lot of opportunity there still.

The second one is ALTUVIIIO. We have reached blockbuster status with ALTUVIIIO in 2025, and we see continued growth for ALTUVIIIO. It's the most switched-to product in the heme A space and really something where we see a lot of opportunity for growth still going forward. And then Sarclisa, where -- in multiple myeloma space, we are getting into earlier lines. We're now -- we've now launched a subcu formulation for Sarclisa with an on-body injector, which we believe from a physician experience, but also from a patient experience perspective can really help differentiate us from Darzalex. So those are the ones that I'm excited about that hopefully will drive continued growth in the future.

Okay. Amazing and Belen has spoken a lot about the, kind of, Phase II to Phase III gate when we think about R&D and more rigor and being driven by the science. So how early can commercial be involved in the decision-making, lets say, it make sense scientifically but the commercial hurdle, it doesn't meet it or it may not be attractive in your view. What role is commercial now playing at the Phase II to Phase III gate?

Yes. So Paulo and I really believe that this is a partnership between commercial and R&D. And that's the way we want to work. We co-own the TPPs, the target product profiles, and we're working really on this together because there needs to be great science, but the science needs to really -- by the time it launches, address an unmet need, be differentiated, as you said, versus the competitive set that you will likely encounter and then have sustainability to it over the time frame that you have when you commercialize it. So that's how we look at things.

There is definitely a desire for more rigor and more discipline around how we make those decisions to go from one phase to another. And that's what Paulo is very focused on, I'm very focused on, and Belen as well. And that's what we're continuing to work in partnership to get on.

Okay. And perhaps in the last few minutes or just to finish. So we've talked a lot about M&A, Regeneron collaboration. What do you think the market is missing or misunderstanding about the Sanofi equity story from here? And is there 1 asset or program that you're particularly excited about that you would like us to focus on?

So when I think about the story, our story, it's -- I think about the fact that we don't have any meaningful LOEs in this decade. It's going to happen in the earlier part of the next decade. So we have runway. We definitely -- our story is all about increasing R&D productivity so that we can drive internal innovation, and we will complement that with external innovation.

We talked about the desire to go for a later stage and commercial deals potentially to help with that. And from that perspective, I really believe that we don't get maybe enough credit for our pipeline because we have 60 assets -- 60 programs in the pipeline, but I understand why. I understand that we've had some setbacks, and we've had -- we've also made some decisions on not moving forward with some of our assets. I believe those were the right decisions. I'm very convinced about that because if you don't bring meaningful innovation to a market, then you shouldn't move forward with it.

But now it's up to us to actually let -- actions speak louder than words, so we can talk about intentions, and we're very focused on moving forward with some of the things we talked about. And hopefully, next time we meet, we can talk about some of the actions we've been exercising and implementing and that's what we're focused on, making sure that we can deliver on some of the things, some of the plans we have so that you can see that we are literally moving on the things that are key priorities for us.

Okay. Amazing. Thank you so much, Manuela.

Thank you.

Great. Thank you.

Thank you.

Hello, everyone. This is Thomas Larsen from the Sanofi IR team. Welcome to the Second Quarter 2026 Conference Call for investors and analysts. Slides can be found on sanofi.com.

Please turn to Slide #3. Here are the forward-looking statements. We would like to remind you that information presented in this call contains forward-looking statements, which are subject to substantial risks and uncertainties that may cause actual results to differ materially. We encourage you to read the disclaimer in the presentation. We also refer you to our Form 20-F on file with the U.S. SEC and our French universal registration document. You're going to make comments on our performance using constant exchange rates and other non-IFRS measures. Numbers used are in millions of euros and for the second quarter unless we stated otherwise.

Please turn to Slide #4. The agenda for today, we are welcoming Belen for the first quarterly conference call since joining Sanofi. Belen will cover our business and the first reflections as a new CEO. You will also hear from our CFO, François; and our Head of Research, Mike on the pipeline. We've expanded to 1 hour and 15 minutes to allow for the new CEO update and plenty of Q&A. For the Q&A, we also have the support of Manuela, Olivier and Thomas to cover our global business as well as our General Counsel. [Operator Instructions].

And with this, I now hand over to Belen.

Thank you, Thomas. Welcome, everybody, also from my side. As you can imagine, I'm excited to return to Sanofi ready to drive the necessary improvement and lead the organization in its next phase of growth. I'm also looking forward to reconnecting with all of you on these calls and through our wider Investor Relations engagement with transparency and trust. Over the past 12 weeks, I have listened. I have learned and I have completed the critical phase of my diagnosis. We have already started translating those conclusions into decisions and importantly, on near-term priorities. Our teams continue to deliver quarter-over-quarter, as seen by the results. At the same time, I have to fully recognize the challenges confronting us and the need to build strategy that delivers on mid- and long-term growth. And I can assure you that this is going to be our focus, and we will do it with the right sense of urgency.

At the end of the presentation, I will further share my reflections since rejoining Sanofi. And now I will focus on our Q2 headlines. Number one, we delivered strong performance with a double-digit sales increase supported by disciplined cost management, leading to double-digit EPS growth. Based on our strong performance in H1 and as we plan further sales and EPS growth in H2, albeit with a lower level of growth, we are upgrading our guidance for full year 2026, and François will provide additional detail around this transitioning to Slide #6 to go through our quarterly results.

In Q2, we continued to deliver very strong growth with a double-digit sales increase and this is driven by both pharma launches and the continued strength of 2 Sales from our pharma launches were up by nearly 50%, led by Ayvakit, ALTUVIIIO and Sarclisa. Established medicines were stable in the quarter. Dupixent continued its very strong growth at 37% in Q2, and that was driven largely by volume, that means more patients receiving it. Vaccines declined slightly, mainly impacted by a high comparable from last year's influenza sales and that was offset by solid Beyfortus and HEPLISAV-B performance. Overall, we saw good momentum across our portfolio, and we are confident in our growth trajectory.

Turning to recent launches on Slide #7. Our launch portfolio is a key growth driver. These medicines represent already 13% of our sales and grew over 60% in Q2. Let me walk you through the key contributors. ALTUVIIIO continued its strong momentum in hemophilia A and remains the top choice for patient switches in the U.S. Ayvakit continues to expand in systemic mastocytosis, driven by continued growth in the number of patients treated and duration of treatment. Sarclisa is performing well in multiple myeloma, and we are pleased with the recent subcutaneous regulatory approval that is providing greater convenience for patients. We saw a significant contribution from the HEPLISAV-B vaccine, one of our latest additions and the recently launched rare disease medicines, WAYRILZ and Qfitlia are starting to show momentum.

What is particularly encouraging is the breadth of this performance coming from multiple disease areas and the continued growth of both early and new launches. Looking ahead, we have additional launches for these medicines and vaccines in new geographies and thus, we expect this portfolio to continue driving meaningful growth.

Turning to immunology on Slide #8. Dupixent has more than 15 million patients currently under treatment globally and sales exceeded EUR 5 billion in the quarter for the first time. Growth was driven by robust demand across indications and geographies. The U.S. also benefited from a favorable adjustment of gross to net deductions in the quarter that François will also detail. As shared previously, we anticipate the growth rate to moderate in the second half of the year as newly launched indications annualized and comparables become tone.

In the U.S., Dupixent remains the #1 prescribed biologic across important prescriber groups with the recent U.S. approval in chronic spontaneous urticaria for children, we continue to expand the depth of indications. Therefore, we have upgraded our 2030 ambition for Dupixent to around EUR 25 billion sales, a reflection of the continued strong momentum.

Turning to rare diseases on Slide #9. This is an area where I see potential for greater opportunity in the future. Rare diseases seek at the heart of the Sanofi's priorities. Sales in rare reached nearly EUR 1.9 billion, up by 24%, and this is driven by Ayvakit and ALTUVIIIO. Most medicines across the franchise grew in volume meaning that more patients are being treated for their rare disease conditions. We recognize that some conditions are more prevalent in specific communities, and this is why we have tailored our portfolio for China and recently launched to innovative medicines there. MYQORZO, a cardiac myosin inhibitor for obstructive hypertrophic cardiomyopathy and rovadicitinib, the first ROC/JAK dual-active inhibitor for myelofibrosis hydrates. We will continue to partner with the rare disease communities, communities that we serve, and continue to bring transformative medicines to patients worldwide.

Moving to Vaccines on Slide #10. On vaccine sales reached EUR 1.15 billion in the second quarter, 5% lower than last year, and this reflects the high 2025 comparison base in influenza. Influenza vaccine sales declined as anticipated due to the 2025 one-offs and a lower southern hemisphere season. But this was offset by the solid growth of our launches. First, Beyfortus grew by 50% to EUR 108 million, driven by a late U.S. season and continued geographic expansion. Second, except grew by 43% on a pro forma basis to EUR 113 million, offsetting the expected impact of birth cohort dynamics of the pediatric franchise. Overall, the performance of Beyfortus and HEPLISAV-B shows the resilience of our vaccines franchise.

Moving to Slide #11. Let me speak about our Sanofi Global 5 units. As you know, around the world, millions of people stick lack access to the medicines they need the most. And Sanofi's global health unit is changing that. Through impact, our non-for-profit brand of WHO Essential Medicines. Our medicines are now available in 30 underserved countries. This is a major milestone on our journey to reach 2 million patients suffering from noncommunicable diseases by 2030. But access to medicines is only part of the story because the unit is also building a stronger health care systems across 40 countries with the highest unmet medical need.

Through a strategic partnership, we have reached 6.6 million beneficiaries. 6.5 million people have been screened, 1.1 and nearly 0.5 million linked to care and we have trained over 40,000 health care professionals and supported more than 1,000 pharmacies and clinics, stronger systems, sustained care. This is our commitment.

I will now hand over to François, our CFO, for more details on our financials.

Thank you, Belen, and hello, everyone. Starting with Slide 13, which is illustrating our strong growth Q2 net sales grew 17.8% to EUR 11.6 billion. This growth was primarily volume-driven and included as well a couple of hundred millions of positive adjustments in gross to net. Dupixent strong and continued patient adoptions and our launches continue to experience solid momentum. Restating for Dynavax and Blueprint sales last year, sales growth would have been around 15%. Our gross margin increased by 3.7 percentage points. This improvement benefited from the reversal of inventory provisions following Sarclisa subcu regulatory approval.

Excluding this item, the increase of our underlying gross margin was around 1.7 percentage points, driven by favorable product mix and efficiency. Operating expenses increased by 13.1%, primarily driven by the blueprint and Dynavax acquisitions. Excluding the impact of this acquisition and one-off costs, OpEx grew at a moderate single-digit rate. As a percentage of sales, OpEx declined by 1.5 percentage points, demonstrating the strength of our cost discipline. OI increased by 35.8% with BOI margin expanding by 3.8 percentage points, driven by growth leverage of discipline and some favorable phasing of capital gains which were roughly EUR 80 million higher this quarter compared to last year. Underlying BOI growth was around 20%.

Finally, business EPS grew strongly at 33.3%. Excluding share buyback and one-off items, the underlying business EPS growth, which supported by solid operational leverage. Now turning to H1. Sales growth was 15.7% and business EPS was 22.7%, partly driven by the impact of acquisitions as far as sales growth is concerned and by positive one-offs for EPS. Underlying sales growth was around 13%. We will face tougher comps in H2, and we anticipate some deceleration of our sales growth. Indeed, we will lap in H2 against a strong sales momentum last year from Dupixent's new indication as well as the consolidation of Ayvakit, which began in July 2025.

Looking further down the P&L. In H2, we expect fewer one-off benefits to gross margin. We don't expect any further Regeneron development balance reimbursement, and we will have reduced benefits from share buyback.

Turning to our 2026 business dynamics on Slide 15. We expect vaccine sales growth to be slightly negative in 2026, mainly crystallizing in H2 due to the usual seasonality of this business. For Q3 specifically, we expect a low to mid-teens sales decrease, reflecting a different distribution between Q3 and Q4 of our respiratory vaccine sales compared to last year. We now anticipate for the full year 2026, a tax rate of around 21%, reflecting the nondeductibility of certain impairment losses on intangible assets linked to recent pipeline decisions. Q2 marked the end of the Regeneron development balance reimbursement. For the full year 2026, the increase of Amvuttra royalties will fully offset this negative BOI impact. Next year, in '27, we will see a negative EUR 200 million BOI gap between these 2 items.

Indeed, we expect a final negative impact from the general reimbursement of about EUR 600 million year-on-year from '26 to '27, while Amvuttra royalties income is expected to increase at the same time by about EUR 400 million year-on-year as well. We are also introducing on the right side of the slide, the Amvuttra royalty projections until 2030 based on Vara consensus. We take note of recent competitor data, which supports our confidence in the long-term potential of this medicine.

Slide 17. We are upgrading our 2026 guidance to reflect a strong business momentum to date. We now expect sales growth of around 10% at constant exchange rates with business EPS growing slightly faster than sales. Before concluding, I also want to update our 2020 -- our 2030 ambition originally provided in 2023. Before reviewing the details, a quick word on foreign exchange. When we set this ambition 3 years ago, we used the euro-dollar rate at that time as a constant currency base line. Today, we are presenting these updated ambitions still at constant exchange rates, but with 2 days rate, which is less favorable than it was in 2023.

With that context in mind, I'm pleased to confirm that we are upgrading our sales ambition for the 3 items combined by almost 10% on a like-for-like basis at constant exchange rates. We raised our Dupixent sales ambition for 2030, which is now expected to reach about EUR 25 billion, driven by growth across all indications. Our ambitions for pharmaceutical launches remains unchanged and should generate about EUR 10 billion in sales, reflecting the strength and diversity of our launch portfolio. And finally, our vaccine business is expected to reach about EUR 9 billion in sales, thanks to our differentiated portfolio and innovation. The EUR 1 billion reduction is split equally between a currency impact and market dynamics. These ambitions reflect our strong commercial capabilities.

Let me now hand over to Mike to cover the pipeline section.

Thank you, François, and hello, everyone. I'm Mike Quigley, Head of Research, and I'm here today representing the R&D organization. We're thankful for the work Human has done in the past 3 years and wish him all the best. We're looking forward to welcoming Paulo in September.

On Slide 19, the status of recent pipeline news. Beginning with regulatory approvals, we received a U.S. label expansion for Dupixent in chronic spontaneous [ unicardia ] in children. A U.S. label expansion for Tzield and Stage III type 1 diabetes and Wayrilz in Japan for immune thrombocytopenia. Sarclisa also became the first anticancer medicine proved in the U.S., EU and Japan to be given either subcutaneously or via an on-body injector. In addition, Cenrifki received EU approval in the treatment of secondary progressive multiple sclerosis in patients without relapses, representing an important advancement by addressing disability progression.

Turning to our pipeline. Several Phase III studies did not achieve the outcomes we had expected, including 2 studies of Dupixent [indiscernible], second venglustat study in Fabry disease, [indiscernible] was stopped early in refractory CIDP based on an IDMC recommendation while the Phase III in IVIG treated patients remains on track. Amlitelimab showed sustained response in the ESTYUARY long-term study, although we subsequently decided not to progress to regulatory submission as part of an ongoing strategic assessment of the pipeline. Finally, Nexviazyme met all study endpoints in infantile onset Pompe disease.

In addition, we received 4 regulatory designations, further reflecting the breadth of our commitment to providing more treatment benefits to patients. With that overview, let's take a closer look at some of those developments over the next few slides.

Now turning to Slide 20. I'll highlight the latest updates from our immunology pipeline. Aligned with Belen's strategic review, which he will discuss in more detail later. In dermatology, the ESTUARY Phase III study of amlitelimab in atopic dermatitis, sustained maintenance of clinical response without relapse for up to 72 weeks with no new cases with Kaposi's sarcoma. However, we have decided not to progress to global regulatory submission as part of an ongoing strategic assessment of the pipeline.

Turning now to divakitug. We plan to initiate 2 Phase II studies in hidradenitis suppurativa and fibrostenotic

Crohn s disease, complementing our focus in inflammatory bowel disease. We have discontinued itepekimab programs across COPD and chronic rhinosinusitis and [indiscernible] programs after Phase II studies in Crohn's disease and [indiscernible], did not meet our internal efficacy expectations.

Now with rare diseases on Slide 21. At ATS, we presented new Phase II data for efdoralprin alfa in AATD amplezema, demonstrating superiority over standard of care in achieving and maintaining normalized functional AAT levels. Dosed every 3 weeks, efdoralprin alfa achieved mean functional AAT trough levels, more than 3x higher than those observed with weekly plasma-derived AAT at week 32. And and was detected in every lung lobe of each participant at week 24. The safety profile was comparable to the current standard of care. These data will support our discussions with the FDA on a potential regulatory submission already in the second half. We also presented highly encouraging Phase III results for Nexviazyme, an infantile onset Pompe disease with 94% of infants alive and free from invasive ventilation at week 52.

Additionally, improvements were observed across all key secondary endpoints with safety consistent with the established profile. These data will support our discussions with the FDA on a potential label expansion, specifically in the U.S. as approvals were already secured elsewhere. And finally, as mentioned earlier, we are pleased that venglustat received U.S. priority review for type 3 Gaucher disease with a target action date of November 25.

Moving to oncology on Slide 22. Sarclisa subcutaneous formulation, including an on-body injector is now approved in major markets across different lines of treatment in multiple myeloma. The Sarclisa CirCLIQ on-body injector, is a compact battery-free device with a hidden needle that automatically delivers the medicine with no manual push and no bioactive excipients. It was designed to enable potential at home administration, either by a health care professional or by the patients themselves were approved and potentially supported by telemedicine. We are pleased with the regulatory approvals in major markets and expect a regulatory decision in China next year.

On Slide 23, let me share the status of our key mid- and late-stage development portfolio. Despite the prioritizations announced earlier, there is a pipeline of important medicines and vaccines for patients, where we continue to advance our portfolio with several upcoming important data readouts.

Let me now turn to Slide 24 and review our expected news flow through the remainder of 2026 and into 2027 and 2028. For the remainder of this year, we expect the final Phase III readout for Sarclisa in transplant-eligible multiple myeloma that will result in another U.S. label expansion. Next year, we expect Phase IIb results for brivekimig and hidradenitis suppurativa, followed by Phase III readouts, including frexalimab in relapsing multiple sclerosis, riliprubart, ECITB compared to IVIg and our pneumococcal and yellow fever vaccines. In 2028, we expect multiple Phase III readouts for Wayrilz and IgG4-related disease, and warm autoimmune hemolytic anemia as well as frexalimab in secondary progressive multiple sclerosis, Sarclisa and smoldering multiple myeloma.

Beyond these clinical milestones, we also anticipate multiple regulatory submissions based on data generated over the coming years, together with regulatory decisions for medicines and vaccines already under review. In representing the research team in Sanofi, we are more focused than ever on starting to deliver meaningful science and patient benefits into the pipeline from our research portfolio. Two external opportunities entered Phase I in the second quarter, with internal projects to follow in due force. This year alone, we plan approximately 1 new Phase I start every 2 months, a meaningful step-up as the changes in research take flight.

Finally, on Slide 25, I'd like to highlight our updated epidemiology data book, which provides the latest estimates across many indications represented in Sanofi's portfolio and pipeline. It is now available on our website. Before I conclude, I'd like to thank all our colleagues in Sanofi R&D with our ongoing commitment in this time of change, and for their unwavering focus on creating new medicines and vaccines for patients.

With that, I'll hand the call back to Belen.

Thank you so much, Mike. So let me briefly -- here are now my first reflection since I joined Sanofi. To start with, let me reiterate my overarching comment that I mentioned at the beginning of the call. I have to fully acknowledge the challenges confronting us and the need to act with a sense of urgency in order to deliver strategy that improves the perspective of the mid- and long-term growth. So I have spent my first 12 weeks on the ground, close to our people, our science, and our stakeholders, the stakeholders will shape some office future.

I am on Slide 27. On people, through either town halls or country visits, I engage with company leaders, and I took these opportunities to take the temperature of the organization as well as to share my own expectations. In this chapter, I have seen firsthand the strong commitment of our employees to Sanofi as well as the deep expertise that we have in the company. Going forward, I plan to build on this commitment to foster a performance-driven culture, greater accountability an ecosystem where people are empowered to make more agile decisions. On science, I also visited R&D sites in France and in the U.S., interacting with our scientists. And importantly, I also spent time in China, a market that is evolving rapidly into an impressive ecosystem that we must further leverage.

When it comes to R&D and the pipeline, it is very clear to me that we need greater scientific rigor, fact-based decision-making, a stronger, even if leaner governance and more effective operations. We also need to strike the right balance between internal and external innovation in order to improve our productivity. That is why I launched very early a comprehensive outside-in portfolio review, which will inform decisions on our pipeline. Now focused on the late-stage pipeline, some of which we shared last week and earlier today. And when it comes to business, our ability to deliver commercial results in the U.S. and Europe, as demonstrated by this strong Q2 performance is a key strength.

We can also capitalize on our local footprint in a deep globalizing market, one with greater accountability and empower country leadership, which will contribute to decomplexify the organization and eventually allow us to move with more agility. Overall, what is clear to me is that Sanofi has core strengths. And it will now be the disciplined choices that we make that will define our net chapter. We are actively developing a comprehensive enterprise strategy versus what has been done before, focus exclusively on the business unit to be able to identify and unlock opportunities.

On Slide #28, I want to highlights some of the early decisions that we have already made as well as some of the key priorities for the months ahead, laying the foundation for our mid- and long-term road map. First of all, on people, we have appointed Paulo Fontoura and accomplished physician scientist and highly respectively to Head of R&D. Paulo is scientifically rigorous and has a proven track record of leading large global organizations and advancing innovative pipeline. Paulo joins a more focused executive committee that was announced last week. Going forward, we will build on Sanofi's employees' commitment to drive the culture of greater accountability high performance and once again, faster, more agile, pack-based decision-making.

On science, we have moved fast making decisions on amlitelimab, as we communicated a few days ago, itekimab and [indiscernible] as Mike mentioned as well as duvakitug where, together with our partners, we have already defined the next 2 indications. The priority now is to fast-track our wider R&D transformation and Paulo's leadership. We are not going to wait for a minute and we are already engaging into the early phases of the R&D transformation, starting, as I mentioned, with the R&D with the late-stage pipeline and strategic review. More rigor,more diligence, better returns and always greater patient centricity.

Our portfolio review is ongoing, and we will share our progress in the quarters to come. It is also absolutely imperative that we intensify our business development and M&A activity in a disciplined way, to enhance our mid- and long-term growth prospects, as I already mentioned before. On the business, we remain committed to immunology, rare diseases and vaccines, and we are evaluating as part of the strategic exercise additional growth opportunities. On rare diseases, I am convinced there is a greater opportunity for us ahead when our strong capabilities and our leadership position in this attractive market segment. In terms of priorities, we will further build on our strong capabilities in the U.S. and Europe.

We will continue to develop in Japan and we intend to expand our presence in China. And you may have seen we have nominated Thomas Triomphe, Head of Vaccines to lead China and our expansion there. Given the vibrant ecosystem and rapidly advancing science, combining decision-making with speed and agility, grow innovation policies and exceptional talent.

Let me talk about something which is very close to my heart. The alliance with Regeneron is of strategic importance for Sanofi. Our discussions to identify opportunities for further collaboration has been active. These conversations are only and will continue in order to determine the best path forward for both Sanofi and Regeneron. And finally, on financials. François has presented the upgraded 2026 guidance as well as the 2030 ambition, reflecting our strong business momentum. We will continue to focus on sustainable profitable growth with a strong focus on cash generation. I see also an opportunity to operate with greater financial discipline and to focus our resources on the top growth drivers. Yet, we are confirming our capital allocation principles, and that includes our commitment to the dividend and our dividend policy.

Moving to Slide #29. Last but not least, from September 1, to deliver on the priorities I outlined, we will have a more focused executive team. The members of the Comex are experienced professionals who will work together will stand behind the strategic decisions of the company in order to shape our future direction. We will have to make disciplined choices and execute those choices with focus in order to create value for our shareholders. Together, we will continue to deliver for our patients our people and all our stakeholders.

Let me close with this. I'm leading an office by delivering complete actions today already after 11 weeks since rejoining while actively working on an enterprise level strategy to strengthen our growth trajectory in the mid and the long term. We aim to engage with you on our strategic direction over the coming months and latest by the end of the year. In the meantime, you can continue to expect that we will operate in a disciplined, agile manner while being decisive and transparent. Sanofi has strength opportunities and also challenges. What we need is focused decision-making, discipline and executing with a sense of urgency and this is exactly what we aim to deliver.

I want to take this opportunity to thank all the Sanofi colleagues I have met today and those who will meet because the openness, genuine feedback, passion and commitment are absolutely invaluable. At closing, I want to thank you for your time before we come to the Q&A. And now over to Thomas.

Thank you, Belen, and I will now open the call to all of your questions. [Operator Instructions] And then with that, I'll hand over to Marie who'll take the first question.

Yes. The first question is from James Quigley from Goldman Sachs.

I've got 2, please. Firstly, Belen, on the Regeneron alliance, you've got the benefit of being external to the history of the alliance and a fresh perspective. So -- and can you give us an idea of, from your point of view, what are the key factors that may be blocking faster progress here in terms of adding assets into the collaboration? And you say you're in early stages of the discussions. But what should we think in terms of time lines? Could we see an update here in 2026? Or is that too early? And then second, on R&D strategy. You highlighted accelerating the R&D transformation is key. What are the key priorities that you have for parallel as it comes into the seat. And similarly, does -- will we have additional resources here, Sanofi's R&D to sales ratio is still at the bottom end of the sector. So is it a case of how much you spend versus where you spend it? Any thoughts there would be great.

James, thank you very much for your question. So look, my impression on the alliance is that, first of all, we have been extremely successful in driving Dupixent and as I mentioned, it is of strategic importance to Sanofi and to Regeneron that we identify the path forward for future collaboration. To be honest, my fresh impression is that as for any partnership, trust is absolutely essential and for different reasons that I'm not going to judge I didn't have the feeling that, that was, at this time, one of the environment in which we have been operating.

So my main objective together with Manuela, who is the Head of Specialty Care here with me has been to rebuild fast, to be able to be transparent to one another, to be able to create a path forward for this conversation. I mean, we speak quite often and while I will refrain myself from making any commitment on timing. As I mentioned, the conversations, I feel are productive and we will further disclose to you whenever an agreement is weak in the future. Manuela, do you want to add anything?

Perfect. No.

So on the R&D spend and where to spend. Look, as you -- as we have mentioned several times, we are right now in the process of reprioritizing our pipeline in order to focus on the strongest science, the highest unmet medical need and where we can create long-term sustainable value for patients and shareholders. And in that context, we are going to in coming months. And in the short term, let's put it away. We are expecting to have moderate increases on our R&D spend. And obviously, as we move forward, our R&D spend will move in parallel to any potential BD or M&A that we may that we may add in the future. So I don't know, François, do you want to add anything to the question? .

No. I think our investments are driven by contribution to growth and returns over time. So I mean this is what will drive our choices be it in R&D or in the commercial side and the industrial side as well.

Next question is from Sachin Jain from BofA.

So just a couple of questions. So first on M&A, you referenced disciplined licensing in BD. So wondering if you could talk about size of deals you're thinking about within your diagnosis is a conclusion of a larger single deal if required on multiple small. Just trying to get a sense of in your early days, how it should change from Sanofi's recent BD strategy. And then areas of initial focus, you called out both rare in China. Is that fair for us to think about as the initial focus? Or could it be broader? I just had a clarification to the prior answers.

So Regeneron, you collapse, which is interesting given the litigation ongoing between the 2 companies on Dupixent on the rebate, which is in early stages. Does resolution of that influence the timing of any progress? And then on R&D, when you say moderate, can I just clarify, is that in line or could R&D grow faster than sales?

So let me start by your first question, which is size of the deals, and I will put François during of our conversations today. So traditionally, Sanofi has been on smaller deals, bolt-ons to eventually increase innovation of buildups. I think our appetite for bigger deals is an option. But obviously, this is something that will be subject to opportunity feasibility and really ticking the boxes of 3 pillars, our strategic fit, the science and the potential to deliver innovation and of course, our financial carats. I guess, today, we are open to eventually consider bigger deals.

Riyadh and China, not exclusively. We are looking at our disease area strategy. So forget about looking at this as immunology and inflammation. We are looking at the disease area level. So where are we strong? We are strong in dermatology, right? And respiratory. So anything that is going to help us and in rare, of course, anything that is going to be helping us move faster and accelerate our mid- and long-term growth will be an option that we can consider, right? China is a priority for us. I mentioned that already.

My own impression is that we have lost a bit of momentum in China. And now we have to catch up and benefit from the wave of innovation that is emerging in China, but we will do that in parallel. We will do that in parallel because our strategy in China may not be completely mirroring the strategy that we are going to have globally because the Chinese market can be served in many different ways. On the Regeneron litigation, let me make only an initial comment. Our current focus is Dupixent, one. Two, Dupixent. Three, Dupixent. And of course, identifying opportunities to work better together, right? This is something that requires is a dynamic conversation. And of course, as being the commercial lead and then being the development need May, after many years, requires some small refinements and this is the focus that we have today. But if you specifically want anything on the litigation, Manuela, please?

Yes. So just briefly, first of all, the litigation focuses on a narrow issue concerning information sharing. And as Belen said, the most important thing and the focus of the alliance is maximizing the opportunity with Dupixent, which we're already doing, as you can see in our Q2 results, continuing to do that. And in the meantime, we're having really productive discussions, frequent discussions, as Belen has shared, and we will continue those discussions. And that's what we are really focusing on delivering on the business collectively as an alliance I believe it's one of the most successful alliances in the industry and then really continuing our productive conversations. This is what we're focusing on, and this is where we put our energy.

And Sachin, just to complete -- to complement what Belen said earlier on BD and M&A. We need to address, obviously, the lessons and learnings from our pipeline lately and the weaknesses that we have. So we need to make our M&A and BD strategy evolve a little bit. So we talked, as Belen said, a few minutes ago in the part of essentially focusing on early-stage assets. We will continue working on that because we need them as well. But we will probably make it even a little bit more interest for net stage assets and potentially commercial assets.

It's not one single deal you talked about. It could be a different structure and where we need to adapt as well to is available but we are certainly BD and M&A will be a way to address the challenge that we are facing with our pipeline, even that the pipeline will not be able to address it with an immediate impact on our financials in the short term. It's less a matter of -- it's more a matter of relevance, as Belen said earlier, in terms of fit with our strategy in terms of scientific presence and financial returns.

So we are not focusing on a given amount, for example, but more on the strategic scientific and financial relevance of what we do. You asked a question about the R&D as well. Is it going to grow faster or in line with our sales in the short term anyway, given the challenges that we have in decision that we have made lately, it will grow to a moderate level of R&D, which means at a lower level than sales. But as we grow over time and as we gain confidence in our capabilities as well, it will certainly increase.

Next question is from Pete Verdult from BNP Paribas. Peter, we don't hear you. Maybe we try the next one for now. [indiscernible]

Sorry, guys. User error, sorry. Peter Verdult here at BNP Paribas. Belen, welcome back. Just 2 questions. Firstly, for Belen, do you remind us how much of the EUR 10 billion R&D budget is discovery versus development? And would there be any appetite perhaps from a strategic point of view to become more search and development going forward than research development at some -- at Sanofi? And also interested how you're thinking about immunology in light of the numerous pipeline failures and your ability to transact outside of the collaboration? And then secondly and more quickly, just for François or Manuela, it's very rare that on Dupixent, there's a 10% miss from consensus between consensus and reported numbers. You've talked about the true-up. We can see volume growth is robust, but it does seem that the 10% to 15% positive impact from either price or channel mix? So maybe François, Manuela, whether could you just give us a bit more detail about what's going on there to sort of give us the bridge from volumes to the report growth?

Peter, I give you a high-level answer to the R&D budget. So the majority of the R&D budget is clinical development. Mike?

Correct. Thanks, Pete, for the question. Belen, you're absolutely correct. That being said, I think there's an absolute commitment to research as a long-term pipeline sustainability and cornerstone of that effort that we have that's been relevant to Belen's statement and strategic review. Another thing I'd add for the benefit is there's not a linear relation between spend and outcome. And so as we think about making the most use of the budget we have to deploy within R&D is critically right decisions go strategically and rigorous, as Bill mentioned earlier, around what we continue to progress versus what we make sure we dynamically allocate away from those medicines that aren't promising. So the key for that is really how we use the capital allocation within the R&D organization.

Pete, on the -- on your second question, my immunology thoughts related to the pipeline failures. I don't think it has to do with immunology, right? I mean we have significant capabilities in that area, context, advisers. I think this goes back to what I said before, we need to be rigorous, right? When you make a decision to go from Phase II to Phase III and engage a significant and get ready to engage a significant amount of capital, you really need to challenge whether or not your data in Phase II are justifying the move to Phase III, right? And you're going to start by dreaming on a target product profile that is not based on rigorous assumption.

So that's basically where we are going to change. And this is nobody's fault. From time to time, my feeling is that there has been a period in which making decisions on these topics on these critical topics for the company, we're not very clearly place where those belong, right? So I am expecting the scientists to make scientific decisions. And I am expecting the scientist to make a judgment call whether the data that we have in Phase II, and I am using this as an example, qualify the asset to go to Phase III. So scientific rigor diligence focus on fact-based decision-making. I repeat, this is where I believe may have contributed or contributed to some of the studies setbacks that we have seen lately and we are going to pay a very significant attention to the way we make these decisions and where do we make these decisions.

And Pete, on the question on Dupixent. So first of all, we don't disclose the breakdown between volume and price. But the growth of Dupixent, which is really, really strong in Q2 as it has been in the case since the beginning of the year, by the way, which is remarkable because we are 9 years after the launch, is essentially volume-led, so this is a very vast majority of the growth. As we said, there was a little bit of tailwind in the quarter due to some pricing adjustment, the traditional gross to net, which did help a bit in the quarter, which is not something that we will see later in the year. But once again, I mean, the growth was largely volume led, which is reflecting what has been said earlier as well, which is the penetration of biologics across indication is review. Maybe Manuela, you want to give some additional color on that.

And just a little bit of a brief add to what François has already said, really driven by underlying demand. And remember, Pete, that when you look at TRx figures from IQVIA, for example, that script data that doesn't fully reflect total demand. The total demand is higher than the script data. And yes, there's fluctuation in the GTA. We have seen -- we have actually focused also on operational effectiveness in the area of GTN to really make sure that -- all of our actions have the right intention get to patients in the right way. That has also contributed and then the one-off GTN topic that François mentioned. But it was really the vast majority was demand driven, and we expect that demand-driven growth to continue at a more moderate growth rate for the second half of the year.

The next question is from Luisa Hector from Berenberg.

I have a couple of questions. Another one on capital allocation. Could you confirm whether the lack of sort of conclusion on the Regeneron collaboration is a barrier to moving forward on any business development and M&A. And then on the 2030, the various components of guidance there, just your levels of confidence, in particular, the pharma launch is now at EUR 10 billion. Could you tell us anything more on the split there? It sounds like that is majority in-market products, but for any pipeline contribution? What is the average risk adjustment applied? And any color on the profitability of that EUR 10 billion versus the prior guidance?

Thank you, Luisa, I'm going to take the first question, which is very straightforward to answer. So we have, at this time, no barriers to related to Regeneron to moving forward on M&A. On the pharma launches, François?

Yes. On the pharma launches is the scope that we disclosed does not include vaccines, by the way, but if we look at it because we don't duplicate we have it as a separate guidance. If we look at it on the scope of the new launches, we will probably reach EUR 5.2 billion, EUR 5.3 billion already in the full year 2026, you can see it with what we have achieved already in H1. If you look at the like-for-like growth, which means restating for our products like [indiscernible] last year. We were growing in H1 at about 27%. To get to the EUR 10 billion by 2030, we need to move to grow on average CAGR by 15%, given that we are on the trend of 27% today.

I'm not worried at all about our capacity to reach the EUR 10 billion and we are just talking of -- by the way, the market -- most -- all of these products are already in the market. So it's essentially a commercial risk. So I'm not worried about it. You asked a question on the profitability of this business. it is already positive in terms of BI, which is quite remarkable due to the fact that we are really in an investment position behind these products to support the growth, but they are already profitable and attractive from a profitability point of view as well.

The next question will be from Graham Parry from Citi.

So just going back to the Regeneron Alliance and BD. When you're looking to acquire immunology assets, can you just talk us through the decision-making process between putting an asset into the alliance versus going into the loan? And in particular, if you were to go with the loan, can you talk about the dynamics of sales force allocation between the alliance and Sanofi stand-alone and would that be a barrier to being able to do immunology assets alone. And then secondly, on R&D, Sanofi's been through many iterations of attempting to improve the pipeline. This is, I think, the third CEO sort of my coverage seen come in with a new plan that sounds suspiciously like the old plan. So perhaps could you just talk us through what you think is systemically wrong in the organization and if and how quickly that can change?

So let me reply very briefly to question number one. So yes, when we go for BD, eventually M&A is -- and of course, our internal respective internal pipelines we consider whether the asset can be better performing within the alliance. Manuela, do you want to add?

I would just add, Graham, that as Belen said earlier, immunology is a large space. And even dermatology and respiratory, we are looking at opportunities within the alliance. We're looking at opportunities outside of the alliance. And if we identify an opportunity outside of the alliance, given the commercial capabilities we have, we are confident that we can build the right structure and then launch these products as we are already doing successfully in that context. So both are options that we are currently actively reviewing as part of the strategic review that's ongoing.

So Graham, I am not exactly sure what you mean the pipeline plan sounds old. I mean I assume that you mean that the R&D productivity issues of Sanofi have gone on for quite a while, right? And be totally frank, we are looking at this as if this -- we are looking at this to take potential learnings from the past. But what is driving us is actually to improve our R&D productivity. And I have repeatedly mentioned what are the focus areas in which we are going to emphasize frequently, as you know, the R&D turning around R&D productivity takes a bit of time.

So we are absolutely convinced that while we reignited our R&D engine, we will have to also accelerate our BD plans and M&A, as I mentioned before. I don't think there is a systemically grown issue in the organization. I think you have to pull the levers, right, be consistent and never complacent and managing risk and the risk profile of the pipeline is going to be something that will be very much at the top of our priorities. Not always aiming for first-in-class and best-in-class, but rather differentiated innovation that can help us move forward.

The next question is from Simon Baker from Redburn.

Welcome back, Belen. It really follows on from Graham's question, and you alluded to it in your response, that you're targeting a fast track R&D transformation. And as you said, transforming R&D is not particularly quick. The fastest I can think of in my time is probably AstraZeneca, which was 4 to 5 years. So what sort of time frame would you put on this? I'm assuming that how [indiscernible] is not a year 0 event. There was a lot of restructuring under humans. So where are we in that transformation journey?

And then a second quick question. All of this, of course, is focused around the loss of exclusivity of Dupixent. And one of the simplest ways of dealing with that is to move the LOE out. Now we know you have a lot of IP beyond March '31 out to 2045, I think. I'd be interested to get your early perspectives on what you think as a fresh pair of eyes on this is what you think the strength of the IP beyond '31 is for Dupixent. And therefore, the more realistic possibilities on when we will face biosimilar competition for that asset?

Thank you, Simon. Look, I can only repeat what I have said before. My feeling is that we have a good understanding of the science and some of the setbacks not A significant number of setbacks are operational risk. Fixing operations is a bit faster than cut recruiting capability -- expert capabilities to the organization. So as Mike mentioned, our research efforts are already paying back. So I am not saying that this is going to be passed, right? But starting by managing operational risk actually would be a variable start. And this is where we are going to do by prioritizing acting and deciding on scientific prefer.

Having the right or the decisions at the right level and managing our clinical operations entirely from an ML perspective, from a study design to conclusion of the trial. And once again, we are not counting that this is going to be fast, so media and M&A together and in parallel to the R&D transformation. On the LOE of Dupi, I want to hand it over to Roy.

Thanks, Simon. First of all, you mentioned [indiscernible] going to '45. Actually, this quarter, we can say it's partner expiration dates going up to 2046. We have a very strong patent portfolio around the many years of R&D, multiple innovations, indications to date. And of course, we intend to be grossly defending. You will appreciate, it's too early to speculate on specific dates for biosimilar entry. I think what I can say based on our experience is that we do not expect. We do expect Dupixent to be protected beyond March 2031, how long were which patterns will hold very early days to be able to speculate, even the typical pattern fights comment be able to give you more details of what is being challenged and keep up the speed of us. But rest assured that we have done our best to make sure that the years of innovation are being protected and we intend to really fight it out.

What I can tell you, Simon, is that we are taking a base case that is associated to the patent to the loss of the product pattern.

The next question from David Risinger from Leerink.

And congratulations, Belen, in on your new role, and thank you for your comments today. So beyond Dupixent target increases longer term, could you please discuss what investors may be underappreciating about Sanofi's future prospects? And then just turning to R&D. There have been a lot of questions. It seems to me that you're simply focused on improving judgments and empowering better decision-making from the ground up. Is that the right way to interpret your comments today?

Thank you, David. So first of all, I believe during my conversation with investors -- what I learned is that perhaps -- we have, for a period of time, over promise and under deliver. That's the bottom line. And this basically keep our credibility tremendously. And despite the results of today for me as a newcomer is really shocking that the strong performance of this company is really not recognized by investors. And that is the only reason that I can fine and that I have been able to delucidate during my conversations with investors. Any other comments in this respect?

Maybe let me add something then that if you look at value in our industry, it's actually driven by to others. One of them is growth. Belen just said it. I mean, we take the box fully on that because we have one of the highest level of growth in our industry. The other one is pipeline, which, I mean, we know and we met disclosure lately on our pipeline. We are aware of the challenges there as well. I think that there is an understanding as well that the market is waiting for not only talks and but actions, and this is what we are working upon. And I think that we are all working in this organization in order to not only [indiscernible] but execute and act, which we will see certainly in the coming months.

On the R&D transformation, yes, I think your interpretation is right, David. Amongst other things, improving decision-making. I gave an example to [indiscernible] on transition between Phase II and Phase III, which is a very critical decision. So you are absolutely right that we want to improve decision-making based on facts, scientific rigor and clear accountability at the science level and at the commercial level.

The next question will be from Seamus Fernandez from Guggenheim.

Congrats, Belen, on the coming-out event here. I guess the 2 questions from my side. You mentioned -- 2 areas that haven't quite been a major focus of the prior sort of management, rare disease. And then also, I think your comments on China are interesting. So I just wanted to clarify 2 things. First, as it relates to rare disease, is this an area that you see for accelerated business development in the context of Sanofi really leveraging the Genzyme history to a greater degree. We've seen very strong development across the board in rare metabolic disorders across the industry, and it's not an area where Sanofi has really participated in some of those new growth opportunities from our perspective.

AAT is a very interesting incremental opportunity, but just interested to understand how you're thinking about staying concentrated in those areas or perhaps broadening? And then on China, I just wanted to clarify, are you specifically talking about accessing the innovation in China? It is something that the industry is chasing quite aggressively, and we're hearing that the bids have maybe gone beyond what would be characterized as value opportunities in the industry? Or are you talking about the market itself and the opportunity to reinvest in the market to drive growth?

So rare, yes. In rare, I believe we have an opportunity, first because the scope is broad. So we are not going to focus exclusively on rare genetic disorders. We are going to further expand to leverage our capabilities and our volume position because we have a top 2 or 3 position in the rare disease market. And I believe this presents an opportunity and is giving us and given our business a significant resilience, I think on China is both. The market is attractive simply because the population is extremely big. So even if the pricing environment is very different than in other countries, the volumes that you can draw from China specific indications or diseases is attractive, right? So that is one element of it. And obviously, take into partnering with companies that are now highly innovative and intend to outlicense that innovation for global commercialization is also [indiscernible] which we are going to be doubling down.

The next question is from Michael Leuchten from Jefferies.

Two questions, please, around the ex comp changes, Belen. One obviously, you're kind of an outsider with prior experience, and you've brought in Paulo as an outsider, but the rest of the Excom change is really internal candidates. Can you talk about sort of pluses and minuses of not having more new blood in that excom to really affect the change. You made a very strong point about this being a big drop and requiring really drastic changes?

And then a similar question, not so, but a question to François on your role now also including BD. What changes does that make for you? Does that just increase the speed of action you can perform at? Does it increase flexibility? Just talk about the sort of options you have now that previously were not open to you?

Michael, thank you for your questions. So on the comment changes, look, I go [indiscernible] when I believe that is necessary to search for a more transformative position, right? And this is what we have done in R&D. However, when you look at the Comex, there are 3 new members, 2 -- the 3 of them from our internal talent pipeline. Manuela, who came a bit earlier than I joined, but she has been in the job for months and came from our internal talent pool. Jamie, who was grouped by Roy and was absolutely ready to take the job and a leader in vaccines who is now going to take general medicine, and that makes a lot of sense because general medicine is a Sanofi specific business.

So over the years, I have learned that you always take less risk when you go -- when you source from internal talent and going outside, but having the optimal blend between external eye and external expertise and internal talent is a very good option, and this is what I have tried to do with Comex. I mean there is a significant percentage of the comments. So now we are 8. Three are new Comex members. So it's a significant percentage with new eyes. And with this, I hand it over of new blood, as you call it.

So on my call, on BD, first and foremost, I'm what the responsibility that comes with it. I think second, we have been very successful in BD and in M&A, just to give you some perspective. Globally, between BD and M&A, we invested EUR 47 billion over the last 8 years. And we have lost EUR 7 billion -- sorry, for the EUR 7 billion. But if we have not lost anything, we would not probably have taken the right level of risk. But we have created the substantial value historically with the remaining EUR 40 billion. And I'm sure we'll have the occasion to discuss a little bit more in details what I'm just sharing with you. So we have a good track core both in BD and M&A. I'm honored as well to take over this responsibility because we know that, as we discussed earlier, BDM&A is part of the challenge that we have in order to address some of the weakness that we have within the organization.

So it will allow the fact that we have it under one roof will allow certainly a better coordination, although it existed before. But I insist upon as well that BD is not necessarily naturally within finance in any organization in pharma, but it can be successful only with a very close coordination and very cross proximity to R&D. This will be my main priority is to make sure that even if it sits within my scope of responsibility, and especially for BD, less obviously for M&A, it has to -- it will work only if we are super, super close to the R&D organization.

The next question is from Richard Vosser from JPMorgan.

Just a couple, please. Belen, you've cut a few pipeline programs. Should we think that the review is now complete? Or should we think about further discontinuations when Paulo joins? And on that remaining pipeline, there are a couple of Phase III assets that read out in the coming 12 months for [indiscernible] part, apologies for the pronounciation, never going to get it. There's some discussion around the chances of success on both. So on frexalimab, there's been discussion on the primary endpoint in Phase III and the ability to be [indiscernible] interested in your thoughts and Michael's thoughts there? And then on [indiscernible] part, the mobilize trial failed, obviously. What are the learnings for that for the VITALIZE trial? Are you comfortable that the patient population enrolled will be responsive to the drug? .

Thank you, Richard. So the pipeline review is ongoing. So I'm not excluding that we continue some additional assets. But we don't have a target number to discontinue, right? We are going to continue to be operating on the basis of scientific merits and risk, as I mentioned, and potential and some other elements. So at the end, after a thorough review of our pipeline, we will be once again concentrating our resources, and this is the bottom line. We will be concentrating our resources in those with highest scientific merit, highest unmet medical need and highest potential. On frexa, do you want to comment, Mike?

Thank you for the question, Richard. On frexa, in the context of the Phase III, we're on track to read out RMS in 2027 in SPMS in 2028. As you referenced, we've been actively working with global regulators to refine our statistical analysis plan really with an eye to testing realistic endpoints of interest for patients given the recent performance of comparators and RMS studies. And rest assured that, that will continue to be a focus. The primary doesn't change in the context of anal relapse rates, but we're focused also on key secondary endpoints, including a 6-month disability progression in the context of the frexalimab readouts that you'll see. With respect to mobilize versus VITALIZE, that's a key question. What I'd say and what we put out was that the IDMC recommended not moving forward in the context of mobilize study because you're unlikely to meet the primary endpoint.

What I can say is that the 2 patient populations between the 2 studies are very different. So in a refractory patient population in the MOBILIZE study, very hard to treat. These patients don't have, unfortunately, anything available to them. I contrast that to the VITALIZE study, either patients that are on IVIG but still are progressing despite a treatment paradigm. And so that comparison versus IgG in that kitchen population is where we're looking at it VITALIZE. Importantly, what I'd also add is that the IDMC looked also at VITALIZE and recommended progressing VITALIZE forward. And so we have hope and we're on track to continue to read that out in the latter half of 2026.

The next question is from Matthew Weston from UBS.

Belen, a warm welcome back. My first question is for Manuela, and it comes back to Pete's question on DP gross to net. Can I push you on your operational effectiveness comment? Has the alliance changed its policy on 340B claims for to reduce access to heavily discounted drug. And I ask that because that's the only thing I can think of that's the really sign improvement in GTN over the first half of the year. And I guess if that is the case, why won't that trend continue? And why shouldn't DP be able to deliver stronger than is suggested by the 10% total revenue guide that we've increased to. And then my second question is about the long-term guidance for vaccines. You bought Dynavax, but you cut the 2030 vaccine guide by 10% to EUR 9 billion. I know that some of that -- but is it because you're meaningfully more cautious on Beyfortus? Or is it the flu franchise? Or is it something else?

Yes. So thank you, Matt, for that question. So when we talk about operational improvements, operational effectiveness, fully agree that it is linked to 340B partially. So as I said, is a portion that is recurring. There's a portion that is nonrecurring. The nonrecurring portion a couple of hundred million. The recurring portion exactly, as you say, is linked to us really looking at how do we ensure patient benefits that reached intended recipients. 340B, enhanced 340B control is a part of that. It's not the only part, but it's a part of that -- a large part of it. And there, we've been thanks to the team successful. And you're right, some of that will continue to occur also in the second half.

The reason why we're talking about a more moderate growth in the second half versus the first half is simply the second half last year was a higher comparison. So we now have a higher base that you're comparing us to. And we are also annualizing some of the indication launches and those 2 contribute to a slight moderation of that growth versus the first half of this year.

Regarding the second question, Thomas speaking. So thanks for the questions. For the 2030 vaccines ambition, you've noticed the change. Indeed, when you look at the trends between the 2 numbers, and you remember, first of all, that this ambition was put in 2023, if I recall correctly. So way before the change of administration. When we look at the drivers of this, this EUR 1 billion difference for 2030 is coming on half of it on a U.S. exchange rate, so U.S. to euro, it's pure financial extent rate.

The second half is driven mostly by U.S. VC, so U.S. VCI evolution, which has turned out to be weaker than expected following the new U.S. administration. And indeed, it's mostly into the respiratory area. So classical flu and RSV. But also, you've seen that CDC and other revenues have shown that there has been a decrease on the vaccination coverage rate of U.S. pediatric vaccines. So if you put both together, that explains the difference. It doesn't change anything on our long-term ambition for vaccines. The fundamentals are very strong. in terms of growing elderly population, our focus on the pipeline on the elderly segment. But indeed, we wanted to recalibrate what has changed with the latest both exchange rate and U.S. overall, I would say, obviously.

The next question is from Florent Cespedes from ODDO.

Two quick ones, please. First, for Belen, you announced that you have discontinued some of the projects, some products in the pipeline. I understand that the portfolio reduced ongoing, but do you have some projects remain in the pipeline where you have strong confidence and would be my first question. My second question for Thomas. On China, maybe could you elaborate a bit on your strategy there? And how do you see the dynamic of this market going forward, which is a little bit soft details.

So listen, of course, as we prioritize our assets, confronting stage of development versus potential, understanding of the biology versus base of development, et cetera, et cetera. You get a picture that classifies those assets into most promising less promising and in the middle of it, right? But I think it's too soon to tell you where are we going to land with a strategic review? I think my -- as highlighted some of the successes on the quarter and also has spoken a bit of the outlook towards next year. So I will remain very prudent until I see data, more data. And obviously, once we have those solid data that we need to see.

We will come back to you to tell you. And as I mentioned during my introductory remarks, we are aiming to give you some kind of perspective in the coming quarters. And obviously, before the year-end, we are expecting to give you a more -- a broader perspective on where we on the strategy and the pipeline. On China, the question for Thomas.

To say a few words. Thanks, Laurent. Don't expect today a big new review of a new strategy for China, as I'm starting September 1. However, I think a couple of things I'd like to highlight. As previously mentioned by Belen. Obviously, China has revealed to be over the past few years, an extraordinary source of innovation with the speed and the ecosystem associated to it being really, really interesting. We want to double down on our efforts there. We started some and we want to accelerate on this. But indeed, alternatively, if you look also at the China local pharmaceutical marketplace, it's also a very interesting marketplace.

First and foremost, because it's a very competitive one. And I'm pretty sure we can learn a lot of things from China that will also be very important in the long term for this organizer moving forward. So excited by both aspects. What I want to highlight, of course, is that this can only be done in extremely close collaboration first with R&D when it comes to innovation. So extremely looking forward to work further with Paulo and Mike on this journey. And of course, for the competitiveness of the overall market, it's going to be effort with all [indiscernible] to be able in China to be as competitive as we can.

The last question will be from James Gordon from Barclays.

Two questions, please. One was on M&A and BD. When you're thinking about which therapy areas to focus on, do you need to have existing strength in the area? So would you still think about doing a deal that in somewhere like oncology where you don't have a big business on urology or it has to be an area where you've got significant scale? And if you're not going to acquire more in those areas, might you even say, hey, we're not going to do those areas and we'll even divest the assets? And on M&A, how much urgency is there to complete a meaningful deal this year? Would you like to have a deal that you could talk to us about by the end of the year? Or might we need to be a bit more patient?

The second question was just about spend. So we've heard that you think you might need to do a bit more R&D. But is there any way that you might not need to spend quite so much. So are you looking to reallocate as if you might be able to take some spend, save from SG&A and reallocate it to R&D or not. So is there an opportunity there? And then just squeezing in the clarification, please. On the Regeneron partnership, is it just about communication and trust or could you -- are you actually looking at the structure of the partnership at all? Is that off the table? Or is that also under consideration?

Let me start with the Regeneron question. So as I mentioned, it's a combination of looking at options to eventually expand the alliance with assets from both sides, right? And in parallel, looking at potential improvements to the collaboration to be more agile and to bring more transparency to the way we operate. And of course, as for any other partnership, as I mentioned before, an ongoing development of trust. So this is exactly what I have repeatedly said during the call of today. Regeneron is of state importance to us. And therefore, we will continue the already initiated conversations to be able to land what is best for both companies.

On M&A, to be honest, it's a matter of opportunity, but you can count that we will -- it will be a combination of a strategic fit. So we will likely focus on our pillars on our main pillars on our core pillars. And BD is directly related to our R&D strategy and focus. So we may, after combine M&A with BD. BD to support platforms and research whenever it's more later stage, it will be complementing what we can generate in side. With those businesses that may not become at the end, a priority growth platform for the company, we will have to evaluate options and this is not [indiscernible]. It can be partnering. It can be offering those business to other companies. So any potential option that will create value for our shareholders. Reallocation of spend to R&D?

Yes, I can take that one, James. But first, I confirm there is no urgency -- dramatic urgency in terms of the M&A. We are not driven by timing objective were driven by returns and contribution to growth. And the same applies to reallocation of resources and resource allocation Obviously, as we said earlier, there might be a little bit of resources available, for example, is a program that we have decided to terminate. We don't need necessarily to the reason rule saying that we have to redistribute that or reallocate it to R&D. Our choices in terms of spend on -- I would rather talk of investment rather than spend are driven by contribution to growth and contribution to return. So if there is a better return on the commercial side of things, what we will do.

So we don't necessarily -- we don't manage fixed budget within a certain category of investments. And let me just give you an example. A couple of years ago, we were still investing a lot, for example, on the commercial side behind Gen Med, but these products are mature. We have decided to reallocate most of it behind growth assets essentially within spec care and starting with Dupixent, and you saw what it means today. You saw it was impressive, almost 18% growth in Q2. So once again, this is driven our choices on cost allocation and investment allocation are driven by contribution to growth and returns.

Okay. So this was our last question. I wanted to thank everybody for your interest in Sanofi. And I look forward to continue the very interesting conversation that we have initiated today. Thank you very much.

Ladies and gentlemen, dear shareholders, good afternoon. I hereby declare open the Annual General Meeting of the Sanofi Company, a meeting which I have the honor of chairing. I would like to thank all shareholders who cast their votes remotely ahead of the meeting and all those currently following the live broadcast. The recording will remain available online after the broadcast.

Joining me here today are Olivier Charmeil, Acting Chief Executive Officer; and Jeanne Kehren, Company Secretary. We are now going to call the bureau I propose that we appoint Jeanne Kehren as Secretary of the meeting. I've asked the company L'Oreal represented by Mr. Cyril Rolling and the company Amundi represented by Ms. Anne Alexandra, the 2 shareholders present holding the largest number of votes to please act as scrutineers a role that they have accepted. The auditors are also attending the meeting. [indiscernible] of the firm represent the Board of Auditors, and they will present their reports. [ Eric Mleiff ] is also attending the meeting. This meeting is filmed and broadcast live on the company's website. Once again, the recording will remain available on the Internet after the broadcast.

During this meeting, I'll have an opportunity to share with you about the Board's work during this year, during which we made major decisions for the future of our company. In particular, you'll have an opportunity to become acquainted with Ms. Belen Garijo, whom we chose to serve as Chief Executive Officer; Olivier Charmeil, our acting Chief Executive Officer, will present about the progress and achievements in 2025; and François-Xavier Roger, our Chief Financial Officer, will share about the financial performance and outlook.

This year, once again, we had remarkable results with strong growth driven by Dupixent and the launch of new products. Although some clinical results in our pipeline were disappointing, our current drug portfolio helps us anticipate robust revenue growth and a financial trajectory that can support our investment ambitions. After the presentation by our auditors, Clotilde Delbos will give you details about the resolutions on remuneration. Then you'll be able to ask your questions before we invite you to vote.

This year, we'll propose resolutions that will have a strong impact on the company's governance. Your -- this Board deeply believes that the decisions made and subject to your approval will help us build the future of Sanofi and ensure its future success in the mid and long term. I will now give the floor to Jeanne Kehren for a few details about how this meeting will unfold.

Thank you, ladies and gentlemen. Dear shareholders, good afternoon. Shareholders have signed the attendance register at the entrance, both in their own names and as proxies. According to the attendance register, the shareholders present or represented hold more than 1/4 of the shares carrying voting rights. We have a quorum, therefore.

Indeed, together, they have 851,165,471 shares or 71.18% of shares with voting rights and 98% of usable voting rights. Consequently, although the quorum is not yet definitively established, it is already clear from the attendance register that the meeting is duly constituted and may validly deliberate.

On the desk, we have a copy of the notice of meeting sent to registered shareholders, copies and acknowledgments of receipts of the registered letters with acknowledgment of receipts sent to the statutory auditors, a copy of the B dated 13 March 26 containing the notice of meeting, a copy of the Journal of Legal published on L and the BLA of 8 April 2026 containing the notice of meeting, the auditor's reports, the attendance register for the meeting, proxies of shareholders represented as well as all documents required by law made available to shareholders at the registered office of the company within the statutory time limits and sent to those who requested them.

The agenda is set out on Page 8 of the Notice of Meeting. Detailed explanations on the resolutions are set out in the Board of Directors' report, which is on Pages 9 and following of the Notice of Meeting, which is available on our website. No draft resolutions or items of the agenda have been submitted by shareholders.

Finally, you've received either from or your financial intermediary all the documents required by law and related to this meeting. I will now give the floor back to the Chairman.

This is the third time that I've stood before you as Chairman of the Board of Directors. The year 2025 confirm the upheavals happening in our industry. The pharmaceutical industry is faced with current uncertainties in the world, but also specific changes. In particular, we've had to adapt to decisions made by the U.S. administration beyond the threat of tariff duties, the so-called most favored nation principle, imposing a sort of price index on drugs in the U.S. on the prices of a panel of OECD nations has become a major challenge for all pharmaceutical companies.

We were able to find an agreement on this topic with the U.S. administration, which preserves the patients' interest as best as we could and also for the company in the next few years, but this will probably remain a major question. China kept asserting itself as an innovation powerhouse with extremely quick development in biotechnology companies, many of them also leveraging intensive use of artificial intelligence. At the same time, we've seen the yet nascent emergence of a European reaction and some companies like -- some countries like Germany and Denmark have committed to increasing the price of drugs to maintain their access to innovation in spite of fiscal pressures and growing tension between social expenditures and military expenditures.

European institutions are becoming aware and have begun taking into account the societal and economic challenges associated to these upheavals with, at the same time, the expected aging of their populations. Whatever the upcoming political changes in U.S., it seems unlikely that the price of drugs will keep following the same momentum as in the past. We need to prepare for gradually stronger constraints on drug prices.

We will also need to carry on adapting our strategy to geopolitical constraints coming from the fragmentation of global trade and protectionism of all kinds that is emerging. More than ever, this environment requires that we carry on transforming to strengthen Sanofi's innovation capabilities in terms of R&D and to improve our operating efficiency. The digital transformation and the use of artificial intelligence as well as the exploration of partnerships with China have now become 2 fundamental levers that we need to keep actuating to ensure our sustainable success in the medium and long term.

Our ability to adapt and the application of our strategy will allow us to carry on using current and emerging opportunities in terms of innovation, technology and growth for our company. Against this backdrop, we have looked at our priorities for the next growth phase in the group and the best leader to lead this new phase. Paul Hudson's term as a director being up seem to be the best moment to take stock of the past 6 years and to define expectations in terms of leadership for the next few years.

I will discuss this decision-making process later in my presentation. But first, a few words about this Board of Directors, and I would first like to thank all our directors for being here today. In 2025, the Board of Directors had sustained activity with 14 meetings and a remarkable attendance rate for its members as well as, for instance, also 14 meetings of the Scientific Committee. Conversations in the Board, strategic seminars as well as training sessions matched our strategic imperatives and the specific points of priority focus that we had identified last year, capital education, business development, mergers and acquisitions, productivity and governance of research and development, digital and artificial intelligence, changes on the U.S. market and China strategy.

The Board has developed a real team spirit over the last few years. This cohesion helped us leverage as best we could the diversity in skills and experience represented within the Board. Regarding the makeup of the Board, first of all, we suggest that you reappoint Christophe Babule and Jean-Paul Kress, who bring remarkable contribution to our work. the former with his strong financial expertise and in terms of management of a large international firm, the latter with the entrepreneurial and scientific knowledge for his rich and long career in the pharmaceutical sector. Patrick Kron, Independent Director and Chair of the Nominations, Governance and CSR Committee is ending his third term today, and he will leave the Board. After 12 years serving the Board, he can no longer keep his status as Independent Director, and we wish to keep a high ratio of independent directors. On behalf of the entire Board, I would like to warmly thank Patrick Kron for his decisive contribution to our work as a director and as the various in the various chairmanships and the committees that he had, especially within his involvement in the major decisions for the company's governance.

Personally speaking, I would like to say that his astute judgment and his experience as a leader were very precious to me. Thank you very much, Patrick. Based on the recommendation of the Nominations, Governance and CSR Committee, the Board of Directors decided to submit to your approval the appointment of Christel Heydemann as an Independent Director. Christel Heydemann is the CEO of Orange Group, and she will bring her specific perspective as CEO of a listed company in France to the Board, who is facing all major international challenges and also her experience in the technological transformation at large scale. Her understanding of digital uses and the development of AI are strategic priority goals in the changes in the Board's skills.

And so we are delighted to welcome her on board the Board. Christel is with us, and please introduce your quickly introduce yourself quickly, Christel?

Thank you, Mr. Chairman. Dear shareholders, I am, of course, delighted to join the Board as -- can you hear me? Is the microphone working? Yes. Yes. Is it working? Yes, better. Dear shareholders, I'll be delighted to join Sanofi's Board of Directors. As Frederic Oudea explained, for 4 years, I've been leading the Orange Group. Orange, of course, in France is a cell phone carrier. We are the #1 cell phone carrier. We are in major European countries in 18 African countries. We are present in cybersecurity and business services in the whole world.

So of course, we're going through the same upheavals as all major firms on the French index. I trained as an engineer. I served my entire career in French firms, but with a strong international aspect, and I was in Alcatel and Alcatel Lucent. And before I became a Director at Orange, I was the CEO of Schneider Electric in France and then in Europe and so with experience in industry. And once again, I'm delighted to be with you today.

Thank you so much, Christel. If you approve the resolutions put to your vote, we'll have a Board that aligns with our aspirations in terms of skills, in terms of gender diversity, 57% of Board members or employee representatives are women. And as I said, we aim to maintain a high independent ratio for our directors.

Amongst the major resolutions put to your vote, we suggest that you approve the appointment of Belen Garijo as a Director. The Board decided to appoint her as CEO to replace Paul Hudson from the 1st of May onwards. This appointment and this suggestion are the outcome of a highly planned and meticulous process. As I mentioned in my introduction, we anticipate this moment when we would take stock and reflect on our strategy when Paul Hudson's reappointment was put to a vote as a director to identify the best leader for the next growth cycle in the firm.

The Board and the committee, the Nominations, Governance and CSR Committee had started from the second half of 2024 onwards, a detailed review of succession plans with the use of a first outside consultant. This step led us to conclude that we had many internal talents but that they were not quite ready to reach the level of CEO. We then extended the exercise with a first tally of outside potential candidates. And then at the end of 2025, with the help of a second consultant, we updated a final list of potential candidates, which the Nominations, Governance and CSR Committee met. Then after interviewing the various candidates, the Board recommended that the Board hear the best outside candidates, namely Belen Garijo.

The Board had previously heard Paul Hudson, who had an opportunity to present his experience and his strategic vision for the company for the next few years. As a conclusion of this highly structured process, the Board considered that Belen Garijo was the best candidate to lead the company for the next few years and take up the next challenges. This decision was motivated by Belen Garijo's undisputed expertise and experience, especially in the area of R&D, her successes and initiatives, especially in China and the digital transformation and her performance and transparency culture.

At the end of the process, of course, the Board shared its conclusions with Paul Hudson, it was an opportunity to thank him for the work done during his 6th year as CEO. The Board of Directors is acutely aware of the major challenges that we need to face in an always more uncertain environment and our determination to guide the company towards more productive innovation, more rigorous transformation execution and demanding operations management to keep growing and preparing the trajectory beyond Dupixent. We are highly confident about our ability to take up these challenges successfully under Belen Garijo's leadership.

During this change, we aligned the duration of the terms as CEO and Director, both will now be for a duration of 4 years. We also changed the remuneration structure to better reward long-term value creation. And then to allow for this nomination, we suggest that we align the age limit conditions for the CEO on those of directors, which decide that the person needs to be under 70 years old at the start of their term. I would now like to come back to the strategic outlook for this new term.

They are based on 4 essential priorities, which will guide Belen's action for the next 4 years. First of all, strengthen the strategic framework in order to optimize capital and resource allocation, both for internal and external capital investments. Then to give more substance again to the development product pipeline to help the next high medical value product generation emerge and to strengthen R&D, governance and productivity.

Thirdly, keep transforming the group, especially in the area of digital and artificial intelligence by leveraging fully the innovation capability in China. And finally, develop our internal talent by promoting a transparency, discipline and rigor culture. This ambition is necessary to ensure that our company is sustainable and resilient. It is with a high sense of responsibilities and values, our values that we made highly structural decisions to carry on transforming Sanofi to ensure its future. Now I'll give the floor to Belen to let her introduce herself.

Thank you, Mr. Chairman. Ladies and gentlemen, dear directors, dear shareholders, ladies and gentlemen, I would like to thank you for having me today. Thank you for giving me the opportunity to take the floor before you. I am fully aware of how important this moment is for you and for Sanofi and for you as shareholders. I'm also very happy to be back in Sanofi, a company that has profoundly marked my career a company I am very -- that is very dear to my heart and a company I've kept following over the years.

I would like to introduce myself and share with you my conclusion and my findings, my ambitions for Sanofi, i.e., define and implement a clear strategy at the group's level, build a strong company with an innovative portfolio and teams that are fully mobilized and engaged to create sustainable value for the patients and for you, our shareholders. If I may, I would like now to continue in English.

Let me start introducing myself, sharing some relevant career milestones and outlining why I am so excited to join Sanofi. I have been a global pharma and life science CEO for over a decade and have worked in the industry, in the pharma industry for more than 30 years. I have lived and worked in more than 7 countries, including nearly a decade in the U.S. I started my career in research and development, which has remained especially close to my heart and have held different executive roles across my career with national and international rem.

In 2013, I joined Merck -- sorry, in 2011, I joined Merck's Healthcare division and became the CEO of Healthcare for Merck in 2013. I successfully brought the business back to growth by reprioritizing and significantly pruning the pipeline, the R&D pipeline, identifying several future blockbuster candidates and reshaping the overall portfolio of Merck. As Merck's Healthcare CEO, I drove clear improvements with a focus on clinical development that yielded 3 launches in 2017 alone delivering 3 blockbuster drugs with over EUR 1 billion sales annually.

In that context, China was an area of particular focus for me. We built a business in China almost from scratch, taking the business from EUR 200 million in 2012 to nearly EUR 1.3 billion in 2024, making China the second largest market for Merck after the U.S. In 2021, I became Merck's Group CEO, repositioning the business towards higher growth with a comprehensive group-wide M&A agenda and a stronger innovation muscle.

I also led the rollout of artificial intelligence across the company, which took up skilling thousands of employees across all functions and sectors over the past 2 years. In parallel, I led the transformation of the organization together with my team, simplifying the operating model, building a stronger global functions and most importantly, a high-performing executive team, and also doing that in a context of cost discipline and delivering meaningful cost efficiencies. This element translated into a stronger financial performance with revenues and profits up 20% and shareholder value creation with EPS up by 31% and dividends up by around 50% in the period between 2020 and 2025.

Let me also speak briefly about my relevant and favorite leadership principles. I would summarize them under the header of the 3 Ts: truth, trust, transparency. For me, truth is being data-driven and fact-based. Realism and boldness are no contradictions. And as scientists in our industry, we know better than anyone that following data will get us much further than wishful thinking.

Trust is the fabric that underpins all productive team constellations. Trust is at the core of high performance and a truly collegial team. Trust is critical to mobilize an organization as leaders and to ensure that everybody, our teams, our employees deliver the same plan especially in the challenging and volatile times that the industry is going through. Trust is required to invest in talent, especially in some of the less evident high potential choices I deeply believe in making and trust is paramount in the relationship between the CEO and the Board. This brings me to transparency.

I deeply believe in ongoing transparent engagement with the Board as a true thought partner. I do not believe in surprises, silos or share cuts. And this is what the Sanofi organization, the Comex, the Board and you as Sanofi's key shareholders can expect from me. My experience, my track record and leadership principles are, I believe, directly aligned with Sanofi's strategic priorities.

Earlier in my career, I spent 15 years working at Sanofi and predecessor companies. I held leadership roles across the group's European and global operations, including Vice President of Pharmaceutical Operations for Europe and Canada. I also led the successful integration of Genzyme, a transformational step that repositioned Sanofi towards higher value specialty care and innovation.

But I left Sanofi 15 years ago, and that is a long time in our industry. I know I will find a very different company operating in a very different world. My time here was an important and a highly treasured part of my career, yet I come back not as an insider, but as a seasoned pharma CEO ready to drive profound change and to lead Sanofi into the next phase of growth. And I am very excited to get started.

Today, Sanofi has strong foundations. To mention some, global reach and leading positions in key therapeutic areas, solid revenue streams and good financial discipline, a high-quality scientific base and high-quality teams. Sanofi has all the ingredients that are needed to create long-term value and play a leading role in shaping the future of our industry. And this requires clear strategic direction and disciplined execution.

We must strengthen the productivity of our innovation engine, take the right level of risk and consistently translate scientific leadership into high-quality sustainable growth in a post Dupixent era. R&D will be a major priority, requiring a total focus on high-quality and competitive products and a stronger alignment across strategy, capital allocation, digital and artificial intelligence capabilities.

As you know, the geopolitical environment is changing at an unprecedented speed, and China is emerging as a critical source of biopharma innovation. We need to capture this opportunity with a future-proof portfolio, operating model and organization. And U.S. policy and tariffs are reshaping the global footprint of economics and the industry. Addressing these internal and external challenges will require strategic clarity and top-performing leadership teams.

Importantly, these are the areas in which I bring experience and track record and where I am confident we can deliver meaningful progress. Dear shareholders, I will set clear priorities and an ambitious road map for Sanofi. My approach will combine disciplined near-term execution with a focus on the longer-term strategic transformation of Sanofi's R&D, operating model and technological backbone.

I will be clear on where we stand and together with the team, communicate our strategic direction with transparency, with discipline and with consistency. On that basis, I will keep you updated on the timing of future communication with investors in the coming months. My goal is to create a stronger, more innovative Sanofi ready to deliver sustainable growth. And I am confident that we can lead Sanofi to achieve this goal and to continue to create value for all our shareholders.

My confidence is based not only on experience, but on the quality of the teams that we have in the company and the values we share across the organization.

This will be for me a real pleasure to be back in Sanofi. And I'm delighted to be able to be -- to write with you the next step in the company's development. And I will -- I promise that I will have a better mastery of French in the future. I'd like to thank you for your attention and for your trust. Thank you.

Thank you, dear Belen, for sharing with us today your strong personal belief and how much you care about this mission personally, I wanted to end this introduction on thanks to Olivier Charmeil, who brilliantly served as Interim CEO to ensure the continuity of business and to prepare for Belen Garijo's arrival in the best conditions. Thanks also go to the management and leadership team who maintained this company's strong momentum during the period.

And finally, over the year on the various sites, I've met many Sanofi people whose commitment and pride to work for this firm convinced me about Sanofi's ability to carry on transforming and growing even in a complex and changing environment. And finally, once again, I wanted to share how determined and trustful I am about our ability to successfully build Sanofi's future in our new growth cycle. Thank you for your attention, and I will now give the floor to Olivier Charmeil after a short video about Geraldine, a patient living with chronic obstructive pulmonary disease. Thank you so much.

[Presentation]

Good afternoon, everyone. It is my pleasure to welcome you to this AGM for 2026. For those of you not familiar with me, it was my privilege to join the company more than 30 years ago and to join the Executive Committee more than 10 years ago.

Joining and representing Sanofi at this time is an important responsibility. The present conditions is my opportunity to share with you some thoughts. You often referred to revolution in the pharmaceutical industry and Sanofi had its share of it, both organically and outside with its determination to use technology as a service of health. But the word revolution is justified.

Indeed, the world is experiencing turbulence, geopolitical tension and economic uncertainty, public health challenges combined with an aging population and yet. At the same time, this is an unprecedented period where the combination of science and technology bring about evolution in our field. Revolution or rather development in artificial intelligence is providing an incredible breakthrough moment.

It's not just a matter of changing the way in which we discover drugs or produce them in our plants or step up clinical trials. It's more than that because we have a huge field of new opportunities in terms of diagnosis, prevention, forecasting and support, and we're only seeing the beginning of this. This technological and scientific revolution is something that we are building ourselves.

It's not something we can see from the outside because we have everything we need. We have outstanding teams, a sound financial base and of course, an expertise and a culture of scientific excellence, which has always been our hallmark. We are a pharmaceutical company. We are based in France, and but we do have an international footprint because we bring together European, American and Chinese scientific heritage to maximize our global impact.

And this unique position provides a valuable asset when it comes to address our next stage of growth in a fragmented world, of course, both in terms of research and innovation, not everything succeeds and certainly not the first time around. It's a very science of nature. It works by trial and error, learning, more often errors than trial, and that makes us stronger. But what counts at the end is what we learn from all this.

Back in 2025, we achieved significant milestones. And before we go through these milestones, I would like to thank all the Sanofi teams in France and around the world that work every day with passion at the service of patients. Your daily commitment is the very reason why today, we're in a position to proudly share with you the results we have achieved and look to the future with confidence and realism.

Let's take a closer look our achievements in 2025. Over the past few years, we modernized Sanofi in depth. We prioritized our portfolio. We refocused and digitalized our production network, and we simplified our commercial footprint. Our culture is more international. It is more daring. And back in -- well, in 2025, in the midst of turbulence, we pursued this effort with only one compass, our is to pursue the miracle of science to improve the life of people. And this ambition determined our choices with a view to remain focused on our 4 priorities.

The #1 priority, of course, was growth, and we did better than expected. In fact, sales grew by 9.9% in 2025. We launched 3 revolutionary drugs and vaccines, Qfitlia, which is the first drug that reduces antithrombin in hemophilia patients, where is, which is the first inhibitor of BTK for immune thrombocytopenia, which is a rare blood disease and, which is the first recombining vaccine for COVID-19, the first one to receive a full approval in the United States and the European Union. Our existing portfolio kept growing, and we'll get back to that, but we also made targeted acquisitions that strengthen our leadership in key therapeutic areas.

Our # 2 priority, of course, was innovation, and the year was marked by significant progress in our R&D pipeline. We also had less positive results elsewhere, but that was all the more reason for us to go further and faster for patients. But in-house, our scientists pushed our pipeline in key therapeutic areas. We achieved a number of regulatory milestones from rare diseases to vaccines. And we also pushed along promising candidates in development stages.

All in all, in 2025, we reinvested almost EUR 20 billion in R&D in M&A and business development. And then that commitment for innovation is global, and this is shown by our CapEx worth EUR 1 billion in Beijing to produce insulin. This is a significant progress for millions of diabetic patients, and it demonstrates our ability to build resilient supply chains solidly based in the largest markets in the world.

Our #3 priority was to do with operational efficiency and the modernization, the continuous modernization of our company. We want Sanofi to become a biopharmaceutical company that includes artificial intelligence on a large scale and throughout our value chain. And one of our largest successes over the past few years is the building of our modulus plants in France. And in Singapore, this is unique in the world. This was designed by Sanofi's own engineers, and they are entirely driven by outstanding teams, of course, but also by AI.

Because they are modular, they can produce as many as 4 types of vaccines and biological products simultaneously. In R&D, we apply all the power of data and artificial intelligence to make the most of clinical stages of clinical trials, I mean, to work faster and reveal new potentials for assets already in our pipeline.

And then finally, our #4 priority was to reinvent the way in which we work. in 2025, our corporate culture continued to evolve. It has become more international, more inclusive. It has become bolder, more agile. And I'll give you 3 tangible examples. Diversity first. 4 years ago, gender balance or gender diversity was just a program. Now it is an achievement. If you look at all our people, about 50% are women.

And if you look at our top 50 executives, 44% of those are women, and these efforts were rewarded by the International Catalyst Award in 2025. And then confidence, our annual survey amongst our own people achieved its highest rate since 2022 -- since its launch in 2022, 78% of our employees feel empowered to make decisions and 90% of them believe we have built a strong ethical culture.

Finally, simplification and agility are people use artificial intelligence and data on a routine basis to go faster, to save time. And today, more than 1/4 of our people use our own LLMs with more than 13 million conversations generated by AI. 2025 was also a very sound commercial year. We had profitable growth basing -- setting us for sustainable growth for the years 2026 and beyond with EUR 15.7 billion of sales over the year. Dupixent, of course, is at the heart of this performance.

But in vaccines, we also consolidated and reinforced our leadership on flu and VRS, which is responsible for bronchiolitis with our new diversified portfolio of differentiated vaccines. Our new products also had outstanding growth to the tune of EUR 5.7 billion, 34% over 1 year, goes to show the strength of our commercial policies.

Our sales were driven by Beyfortus and ALTUVIIIO reached EUR 1.2 billion. Ayvakit, of course, boosted this trajectory with the acquisition of Blueprint Medicines back in July, the good performance of these launches is a clear illustration of the synergy between our commitment for innovation and our ability -- our ability to implement decisions.

Let's look now at our pipeline. We had 20 regulatory approvals, and we moved -- we had many studies that moved from Phase II to III. 10 new molecules entered in Phase I of clinical developments, including 3 in gene therapy. But there were some setback in 2025 for difficult diseases. Science doesn't always move in a linear way, but failures are not, of course, what defines us. Of course, the main thing is to draw lessons from failures and adapt from that.

In the coming months, we expect several readouts of clinical trials and regulatory milestones that are critical both for the company and patients in such key therapeutic areas as immunology, rare diseases and vaccines. They -- our responsibility as a leading company goes beyond the drugs we manufacture. It reaches out to the world and the communities at large.

And thanks to our global health unit, we've been supplying essential medication in 40 countries where the needs are most acute. In 2025, we treated more than 1 million patients. But of course, there's one success that is worth recognizing. ALTUVIIIO, which is the first single-dose treatment for sleeping sickness replaces weeks of medication by a single shot.

We got the EMA's approval in February, and we're working with the Sanofi Foundation and the World Health Organization for this to be distributed free of charge to patients. For Sanofi, climate action and work on patients are not separate operations since more than 70% of our portfolio target diseases that are exacerbated by climate change and environmental disruptions.

And we can make a difference by reducing our own carbon footprint back in 2025, we were able to cut by 49% our Scope 1 and Scope 2 emissions. We're getting close to our objectives of 55%, and we have 86% of renewable energy. And of course, we have a clear objective. We want to reach carbon neutrality by to be carbon neutral by 2045 throughout our value chain.

Ladies and gentlemen, dear shareholders, it is necessary to take a step back and look back at our performance. This is no easy task, but this is our chance to see the reasons that guided our past choices, and I hope we will shed light on our ambitions. As I said, 2025 was a sound performance. We made progress towards our ambition to become a global leader in key therapeutic areas.

And these performances are a clear incentive to pursue our transformation and adapt Sanofi to future challenges, especially in the fields of R&D and artificial intelligence. Nonetheless, there's still a long way to go because we have high ambitions for our patients, for the communities, but indeed, for our own people and shareholders.

And none of these achievements would have been possible without strong Sanofi teams committed to our ambitions in France and throughout the world. I would like to thank them from the bottom of my heart on behalf of the Executive Committee. And I would also like to thank Frederic Oudea and the Board of Directors for their advice as well as our shareholders and partners for the trust they have bestowed upon us. Thank you.

Well, thank you, Olivier. And now I'll give the floor to François-Xavier Roger, will tell you about financial performance for a quick video.

[Presentation]

Ladies and gentlemen, dear shareholders, our numbers for 2025 illustrate our sound economic model with strong growth and profitability. Our revenues were EUR 43.6 billion, up 9.9%, one of the best performance in the pharmaceutical industry. We are in the high end of our guidance and gross margin was up 1.9 percentage points to of sales on the constant ForEx with a favorable product mix and productivity gain, our higher OpEx reflects higher CapEx as well for future growth, especially in R&D and marketing expenses for new products.

OpEx was down in terms of percentage because of our efficiency gains. Operational profit was up 11.9%. Operational margin at 28.1% of revenue. Earnings per share was up 12.2%, not including share buybacks in line with our forecast. If we include EPS, share buybacks, EPS was up 15%. This performance illustrates our ability to boost earnings per share faster than revenues while still investing in future growth.

Over the past 3 years, our growth in volume accelerated and reached 34%. That outstanding growth was driven by our successful launches and by Dupixent, which keeps generating significant growth in volumes 8 years after its launch. Our ability to gain market shares while improving profit margins illustrates the strength of our innovation and our outstanding commercial performance.

Our free cash flow returned to sound levels in 2025 to EUR 8.1 billion, 18.5% of sales. Our objective is to have free cash flow steady at at least 20% of revenue in the medium term. Such strong cash generation testifies to the quality of our performance and our effective management of working capital. One key item here was stock adjustments. We were able to bring this down by 30 days last year. This disciplined approach provides significant financial flexibility to implement our capital allocation strategy.

Our capital structure end 2025 was sound. Net debt standing at EUR 11 billion. We kept a conservative debt to profit ratio around 0.9x and this cautious level of leverage provides flexibility for future growth opportunities even with the AA rating, we redeployed successfully the EUR 10.4 billion from the disposal of Opella in such acquisitions as Blueprint, VisBio, DrandBio and Vigum.

In 2025, we implemented our capital allocation strategy according to 3 priorities: organic capital expenditure, acquisition and shareholder compensation. Let me go through this in detail. We significantly increased CapEx in R&D, in commercial efforts and in our industrial capacity and in the digital transformation. That CapEx will continue boosting present growth and future growth.

As I said, we redeployed the proceeds of the disposal of Opella in strategic acquisitions you have on the screen. These acquisitions strengthened our presence in immunology, rare diseases, vaccines and neurology. Sanofi also compensated its shareholders in 2025 to the tune of the historic number of EUR 10 billion, and this is almost 50-50 between dividend and share buyback of EUR 5 billion for share buyback should be seen in the context of the partial disposal of Opella.

We also proposed an increase in dividend for the 31st year running to EUR 4.12 per share, up 5.1% compared to last year. In 2026, we shall continue our capital allocation policy, in particular, with a new share buyback program worth EUR 1 billion, which we finalized last night. This approach shows our commitment to create value on a sustainable basis and to compensate our shareholders while investing in long-term growth opportunities.

For 2026, we expect revenue to increase by about 7% to 9% and EPS slightly more than that. We expect a negative ForEx effect on revenue, about 3% on earnings per share on the basis of existing exchange rates. In conclusion, let me share with you our ambitions for the -- by 2030, around 3 pillars. Dupixent should generate about EUR 22 billion in sales driven by existing indications, but also the launch of new indications, then our pharmaceutical launches, which should generate about EUR 10 billion by 2030, reflecting the wealth and diversity of our innovation pipeline. Finally, our vaccine activity should generate about EUR 10 billion in revenue with the rich diversified portfolio and differentiated innovations that, of course, is based on our trust to our ability to generate sustainable and profitable growth in the long term. Thank you for your attention.

Thank you very much, François-Xavier, for this presentation. The floor is now to our statutory auditors. will present to us the summary of their reports on behalf of the college. I propose to watch a short video summarizing some key figures about our activity in.

[Presentation]

Thank you, Mr. Chairman. Ladies and gentlemen, good afternoon. I would like to present on behalf of the statutory auditors a summary of the reports prepared for your attention. For the '25 fiscal year, we've issued 6 reports covering the annual accounts, the consolidated accounts, the related party agreements, information about sustainability and finally, 2 reports on transactions related to share capital.

In our first report, we issue an unqualified opinion on the annual accounts for the '25 financial year. Furthermore, in accordance with regulations, we have set out in our opinion reports the key audit matters for the annual and consolidated accounts of Sanofi. Regarding the annual accounts, this relates to the valuation of equity investments. We also issue an unqualified opinion on the '25 consolidated accounts of the Sanofi Group. The key audit matters are 4 in number. There are 4 major points. First, the recoverable amount of other intangible assets. The second relates to the valuation of rebate provisions within Sanofi's commercial activities in the U.S.

Third point, provision for product risk and other disputes and contingent liabilities. Finally, the last one concerns uncertain tax positions. Our third report concerns related party agreements. In that capacity, we have been notified of no new agreement needing to be submitted to your approval in this meeting.

Our fourth report relates to sustainability information pursuant to the CSRD directive. In that respect, our report confirms that we have not identified any material errors, emissions or inconsistencies on 3 subjects: the compliance of the double materiality analysis, the compliance of the published information with sustainability standards called ESRS and compliance with the taxonomy disclosure requirements.

Finally, in respect of the extraordinary part of your general meeting, we've issued reports on resolutions likely to affect your share capital. These transactions fall within the conditions provided for by the French Commercial Code, and our reports contain no particular remarks or observation to bring to your attention, Mr. Chairman, ladies and gentlemen, I would like to thank you for your attention.

Thank you very much, Mr. Waller. I would now like to give the floor to Clotilde Delbos, Chairwoman of the Compensation Committee, who is going to present that compensation policy.

Mr. Chairman, ladies and gentlemen, dear shareholders, good afternoon. I would like to report on the activity of the Compensation Committee. I now am honored to chair, in particular on the aspects related to the compensation of corporate officers detailed in the corporate governance chapter of the universal registration document and reflected in proposed resolutions 9 to 11.

I'm going to start with Resolution 11 and 12. It is proposed in Resolution 11 to increase the maximum annual overall compensation envelope to EUR 3.2 million starting from the '26 financial year. The reasons for this increase are as follows: After analyzing the compensation paid to directors of competing pharmaceutical companies, apparently, Sanofi is significantly out of steps. We have, therefore, wish to align director compensation with that of European and British competitor companies to enable better retention and attractiveness of directors with the essential expertise required, notably for overseeing Sanofi's R&D portfolio and growth operations.

Finally, it was necessary to take into account the increase in the intensity of the Board's and committees' activity given the growing complexity of the geopolitical and strategic environment. Subject to approval of this resolution, the fixed portion of directors' compensation would be raised to 37,500 and attendance fees per Board or committee meeting would increase by EUR 1,500, respectively. Regarding the compensation policy of the Chairman of the Board, Resolution 9, it is proposed to make no changes to this policy. The Chairman's compensation has, therefore, remained unchanged since his appointment in '23.

Regarding Paul Hudson's compensation in '25 Resolution #10, the main elements are recalled on the screen, a fixed compensation of EUR 1.6 million, a variable compensation assessed against previously defined objectives, EUR 2,616, I will tell you more about that and the award of 90,000 performance shares vesting subject to multiyear presence and performance conditions. For the variable part of the compensation, financial objectives representing 60% of the criteria regard sales growth, EPS and free cash flow.

Achievement rates range between 104% and 136%, in line with the company's good commercial performance. Individual objectives representing 40% show achievement rates between 86% and 101%, reflecting mixed R&D results. The overall rate stands at 109%, giving a variable compensation of 2,616,000. Following shareholder votes at the '25 AGM, which showed certain questions about the CEO's compensation policy, Sanofi's governance and in particular, the Chairman, met with shareholders representing nearly 30% of its institutional capital.

Greater transparency on benchmark elements and CSR criteria have been added to the '26 policy to respond to your expectations. Resolutions 14 and 15 regard Paul Hudson's compensation policy between January 1 and 17 February and Olivier Charmeil, Interim CEO between February and April. Those remunerations are in line with the '25 policy followed and will receive a pro rata temporary compensation of EUR 1.6 million and the variable compensation subject to predefined performance criteria.

Those elements will have to be voted by the assembly in '27. He has not been awarded any equity compensation. His departure conditions are in line with the company's policy and have been made public. As for Olivier Charmeil, he retains his compensation under his employment contract. He will get a fixed and variable supplement to align his compensation with the CEO's compensation policy for the period during which he holds the position of interim CEO.

He does not benefit from any other additional compensation elements. Resolution 16, compensation policy for the future CEO, Belen Garijo, as of the start date. This policy will apply for the duration of our 4-year mandate and was amended compared to the previous policy to be more focused on medium-term value creation. The main changes are the following: no sign-on bonus, no entitlement to a supplementary pension plan, equity compensation split in 2 tranches to incentivize enhanced performance and value creation.

I will detail the structure of this share-based compensation in a minute. An bonus of 15% of target annual compensation subject to a performance condition. severance payment capped at 12 months of target annual compensation. The other compensation element for Belen are unchanged in relation to the '25 compensation policy, notably regarding an annual fixed compensation of EUR 1.6 million and variable compensation elements.

Regarding the equity compensation structure proposed, it will be 2 tranches, a long-term plan for the entire duration of the mandate and regular annual plans to reinforce the long-term value creation objective. The total maximum award over the 4-year mandate will be 360,000 shares, which is equivalent to the previous policy but distributed differently.

The long-term tranche entirely awarded in '26 also called long-term tranche covers Belen's mandate between '26 and 2030 and includes 180,000 shares whose attribution will be subject to performance criteria. 80% of those shares will depend on the TSR assessed in 2031 and 20% of CSR criteria assessed in 2030. The attribution of those share is subject to a 4-year presence condition.

Regarding the annual medium-term plans, also called medium-term tranches regard 40,000 shares per year, subject to a presence condition and performance conditions assessed over 3-year periods. The criteria are EPS, FCF, TSR, CSR and development portfolio. Resolution 16, therefore, includes the awards of the 26 portion of both tranches, i.e., 180,000 shares from the long-term tranche and 40,000 shares from the annual plan totaling 225,000 shares. I would like to thank you for your attention.

Thank you very much, Clotilde. We will now move on to the questions-and-answers session. As soon as we have the final quorum, Jeanne Kehren will give it to us.

Before we start the Q&A with shareholders, I'd like to inform you that the Board of Directors received 4 written questions with a group of 4 questions from the forum for responsible investments and a block of 6 questions from a group of asset managers and institutional investors. Questions to the answers to these questions were published on the company's website as per the law. I will now invite you to ask your questions. I'll allow myself to remind you that only shareholders are allowed to ask a question. Please stand up if you can and introduce yourselves. People will hand over microphones for your questions. And of course, like every year, so that everyone can have an opportunity to speak, I would like to ask you to remain as concise as possible and to keep your questions short. Now before we give you the floor, the quorum. We have a quorum of 851,428,895 shares or 71.2% of shares with voting rights and 71.01% of existing voting rights. Thank you very much. Well, once again, I will give you the floor. Maybe #1, please.

Turning to Panel 1. Good afternoon, Mr. Chairman. Good afternoon, ladies and gentlemen. I received the consolidated accounts when I walked in, and thank you for giving them to me. It's not always to receive them. When I look at the consolidated accounts, the revenues were up by 6%. But when I look at your table, I saw plus 10%. Is it an error in the accounts or in your table? I couldn't understand. Then you talked about an increase in the 2026 forecast of about 7% to 8%. But looking at the consolidated accounts, it says that in 2026, sales will be negatively impacted. So who should you believe the consolidated accounts presented by your corporate communications or by what we saw in the table.

Well, be reassured our accounts are truthful. For that, I will turn to Olivier Charmeil.

Well, the accounts that we presented are truthful. Our revenue growth on a like-for-like basis with comparable ForEx is 9.9%. The consolidated accounts reflect changes in currencies and therefore, the impact of the dollar, which last year declined strongly. So these comparable ForEx changes are reflected into a 6% growth. And François-Xavier said that once again, we're expecting a negative ForEx impact compared to a constant ForEx. -- development. That's because of the dollar's depreciation.

Thank you, Olivier. Now question number three, be reassured, I'll go around the room to give you an opportunity to speak. Please ask your question.

Mr. Chairman. Can you hear me? Yes, go ahead. Jean-Claude Muller, I'm a former Sanofi manager. Maybe could we have a bit more volume for the gentleman. It seems that the microphone is not working well. I'm a former Sanofi Manager. On several occasions in your written and oral presentations today, you talked about the lack of performance of the performance deficit in Sanofi's internal R&D. Could you explain why in the last 10 years, this performance hasn't been up to the level of some European competitors, Roche, Novartis, AstraZeneca and even Serier. Thank you, Mr. Chairman.

Thank you. Olivier?

Well, we went through in the last 15 years, major successes, especially the marketing of Dupixent. We have also gone through, especially last year, some results that were more nuanced. We are in an industry where we need to take risk and we need to be able to bring assets to the market that are differentiated for our patients. So this is a tricky balance between taking the right level of risk to be able to be differentiated if we are successful and taking a level of risk on the portfolio that is acceptable. Regarding the last 10 years, we brought a number of products to market. We had a number of successes.

If I was to take 2 or 3 items out of that, our research compared to other firms delivered less. Here, I'm talking about the research part. We made a number of acquisitions. If you look at them over the longer term, I think that we were able to assess the opportunities from the outside as well as other firms.

And also in the last few years, we carried out development operations, trying to find the right balance between upstream phases, Phases 1 and 2 where clearly, compared to the competition, we are in a situation where we have fewer Phases 1 and 2 than our competitors.

And these last few years, we've been working on having access to more early research. In the last few years also, we've been working extensively on making a number of governance changes to make the best development decisions and be quite sure that we design clinical trials that are the most appropriate in order to highlight our differentiation at a given level of risk.

And these last few years, we've also been working, in particular, under the impetus of. We've been working on talent. Talent is, of course, very important in this industry. There is very strong competition for talent and a number of recent recruitments, both in the research and the medical part as well as regulatory, but also development mean that -- and I think I can say that given how long I've been within this company, I think that these recent recruitments put us in a better position than what we had these last 10 years.

So we know very well that turning research around doesn't happen overnight. We have a number of therapeutic areas where we have strong positions, and it will be up to Belen to either consolidate them immunology, vaccine and rare diseases, which are, of course, strong assets for the company and to decide whether we have other opportunities in other therapeutic classes. Thank you for your question. I will look to the center # 2, please.

Hello. I listened to the various presentations. I found it most interesting, but I would like to have clarifications on 3 things. Number one, our new CEO program is very exciting, and I certainly hope she succeeds. But she said earlier in her presentation that in the previous company, she simplified the operations or the operating models.

And I was wondering whether the same should also apply at Sanofi, if she can streamline processes there? And could you give us a few examples? And then for our acting CEO, he mentioned a vaccine that will -- well, that was able to build on R&D -- on COVID R&D. Now I remember reading in the media that the first time around, Sanofi failed to develop a COVID vaccine. Nonetheless, that research enabled Sanofi, and I believe we had a case in point. In the end, this was a blessing in disguise and indeed in turn into a financial success, but I would like to have details about that. And then the last question was about the video. There's a reference to a shortage of drugs in France.

Now I'd like to know what is Sanofi doing to help address the situation for the French public to have access to medication without being affected by the shortage. These are the 3 questions I would like to have. explanations.

Well, thank you. I first give the floor to Olivier, who will take questions 2 and 3. And then maybe, Belen, if you'd like to take the question about simplifying the business model. Maybe you can say a few words about what you did for Merck and the extent.

I mean, it's a bit early, but you tell us. You have been doing a format would be of interest for our shareholders. So Olivier, first, yes, well, regarding simplifying the processes, I'm certain that Belen can certainly make a difference. We transformed. We've been transforming the company. But over the past few months, you can see that the world is changing, and we have to change as well. This is essential.

The second question about vaccines and the COVID-19 vaccine, there were all sorts of factors that delayed our work on recombining vaccines and indeed on the mRNA vaccine. We made an acquisition 3 years ago, indeed. And that enables us now to work on the mRNA vaccine, and we've been working on recombined technology. So there will be -- we'll be able to develop flu and COVID-19 vaccines.

And we can combine this as soon as we can establish effectiveness when you have a combination that can be the equivalent of 2 separate vaccines. So we've been spending quite a bit on vaccines of late. And if you look at the competition and in particular, Moderna, we believe that we can work for combined vaccines, and we'll be ready for this by the end of year 4.

Hang on, it was -- it was more an issue about addressing the shortage of medication rather than innovating -- innovative vaccines. Our access to medication or access to drugs, there's been some tension. And on the one hand, we want to be able to bring innovative products to the patients. But of course, we want to be able to fund development. Development is long-term fair. You're talking 5 to 10 years with significant capital expenditure, EUR 3 billion to EUR 4 billion per drug, and there's uncertainty of success when you enter clinical phases.

The probability of success is anywhere between 5% and 10%. And over the past 12 to 18 months, especially in the United States, we highlighted the fact that the innovation model had to find a financial business model. And in France, you may remember the Draggy report, we found that if Europe is to play an active role in pharmaceutical innovation, innovation should be financed in a sustainable way. Now sorry, maybe let -- let's give the microphone to Mrs.. Again, she's not even in charge.

Yes, you will allow Belen to, well, take a few months. Thank you for this question. Examples because there are certain dimensions, certain different dimensions of dealing with the current complexity and simplification. The first one is the region-for-region approach in which we have invested significantly to put our -- to make the supply chains more resilient.

Obviously, I am mentioning what is public already. And then the most important simplification initiatives that we have put in place are aimed to avoid duplications in the organization. When you have complexity across the different functions and the different business units, making decisions at the right level is very, very, very difficult and tortuous. So there is a cultural component and a cultural leadership and a redesigning of the operating model basically to avoid duplication and make sure that you understand who is making good decisions. I will leave it here.

Yes. thank you, Belen. Now I'm going to reveal a secret of the Board. Anerancois then normally, she is the one on the Board who translates everything into French and English. Anyway, I'll turn to the left here. There's a gentleman with # 2.

Yes, good afternoon. My name is Philippe. I'm an individual shareholder. And you said that there were issues with supplies of innovative compounds. But there's another issue, isn't there? During the financial presentation, we found that some of the gains were because we reduced inventory and just-in-time delivery. But now you have geopolitical challenges worldwide. Isn't there a risk if you have -- if you reduce inventories, there's a risk of shortages, isn't it?

All right. Well, look, let me let Olivier address this, but we were focusing to access to drugs that are available, but innovative drugs and inventory optimizing doesn't imperil access to medication. But there are issues, of course, with the current developments. There may be risk for international trade, of course.

Right. Well, geopolitical tensions will prompt us to reconsider maybe our industrial footprint and investment decisions are long-term decisions. Now the world is in a way, fragmenting. And so we have to allocate industrial investment to make sure that we invest on innovative drugs and make sure that at the end of the day, our patients have access to the right medications.

So we've been investing in France, in Europe. Indeed, more than 12 months ago, we decided to allocate capital expenditure in an insulin plant in Germany. So we've done that. And as I said during the presentation, we've been also allocating capital in China to pursue development in China for diabetes. But also a few months ago, we indicated that we would continue investing in the United States. That is our second largest market.

So in a world that is dividing up as it were, we need to have indications developed in different regions, and we are allocating this very carefully. Indeed, we want to make sure that our capital expenditure strategy is relevant.

All right then now I'm looking to my left, and I see -- I'll give the floor to the gentleman on the other side. But sir, first.

Yes, hello. My name is Mark, and I have been a shareholder since the last century, and I have a question about and Euro API. You are and Euro. You are an independent shareholder. But aren't you concerned about following the same trend as EuroAPI?

Well, first of all, thank you for being so loyal to Sanofi, but Olivier will show that things vary greatly from one market to another. But Olivier, you can address this.

Yes. Well, there are 2 or 3 things to be said about this. The disposal in 2025 was successful. As you may know, CDNR in the United States has 50%, and we have 49.2% and the French BPI has 1.8%. Opella's numbers are good. I spoke with Opella's CEO. And in one of our recent executive committee meetings, we're able to look at the performance. Now fair enough, the market was more challenging in 2025 and yet. Opella was in a position to deliver EBITDA pretty close to its guidance. Now the second aspect is that the beginning of the year, of course, 2026, well, is in spite of a challenging market, has been pretty good so far. So we're not concerned about Opella's performance.

It's been pretty good. The second issue you've raised is Euro API. Now EuroAPI finds itself under pressure financially. However, it is now under control. EuroAPI had to address major challenges, in particular, a plummeting revenues. And of course, they had to have a new plan, Focus '27 to adjust the situation in the medium term.

Now we supported Euro API. We produced a hybrid bond worth EUR 200 million as part of our relation with EuroAPI, but this is an arm's length position. So the operational transformation is underway. It's continuing with a simpler portfolio. And in short term, at least there's no cash problem because in spite of EuroAPI's present challenges, they have enough cash to cover all the necessary restructuring, and they will be in a position to improve profitability.

Well, thank you, Olivier. I move on to the right. Okay. The lady on the first row.

Yes, my name is. I'm an employee and a shareholder. I have a question about artificial intelligence. I would like to know whether the effect of artificial intelligence has been fully assessed on the environment that is are there environmental consequences?

Well, it's tough to be a CEO because then you have to take all sorts of questions. Well, look, a few comments. We -- over the past few years, we've been investing in information technology and artificial intelligence. So we want to make our foundations more stable or more reliable, but we've been working on artificial intelligence and digitalizing our processes.

Now if we compare our performance with the competition in terms of IT and digital technologies, the capital expenditure is above median. Now there are areas where we've been investing. So of course, artificial intelligence, but also in research and that we believe that AI will be a transforming technology when it comes to selecting and optimizing targets, but also for development, there are -- well, put it this way, artificial intelligence should step up a number of clinical studies.

We can have a better selection of centers and patients. There's also industrial innovation. We've been -- well, we have a number of projects underway, the purpose of which is to integrate data to have -- to improve production and yield on factories and biopharmaceuticals. But the question is, I mean, and we all know this that the use of artificial intelligence uses up a lot of energy, of electricity. And we want our electricity to be clean and renewable. And I can assure you that we are very mindful of this.

And so we use AI in a proper way, and we only resort to that in those areas where we feel that we can achieve productivity gains or address issues that we wouldn't be able to address effectively without it. Yes. Well, thank you. When you look at that issue for the pharmaceutical industry, the potential benefit to make findings faster at a lower cost for medication that can help patients, especially for rare diseases, especially in terms of CO2 emissions. This -- it's well worth it. There's no issue.

I believe your next door neighbor wanted to ask this question.

I'm an employee and shareholder of Sanofi. You discussed the outcomes of Paul Hudson's term and the process that led to a change in CEO. The question is, what are the reasons that led the Board of Directors to choose a fairly fast departure or maybe a horrid departure for Paul Hudson with the payment of a several million euro severance package compared to an option to the option of waiting for his term to end 2 months later.

Well, here, that was very clear. That's very clear. The challenge was to allow Belen Garijo to prepare for her arrival as quickly as possible. I'll remind you I reminded you that the challenge was to determine the best leader, the best CEO, man or woman for the company for the next 5 or 6 years, for the next growth cycle.

And compared to your question, sir, what we looked at, in particular, was the profile from R&D for Belen Garijo because that's probably the major challenge for the company, and there are a few pharma CEOs with backgrounds in R&D, and that was a major aspect.

And then when you say that -- when you tell a leader to leave, it's never really nice to stay on. But we wanted to prepare for Belen Garijo's arrival as quickly as possible from the 1st of May onwards to help her assume the position as quickly as possible. She could meet the team. She could prepare her arrival in the best possible conditions and for us not to waste any time because a paradox is that we are very confident about the results for the next 5 to 6 years with Dupixent.

So you might feel that we have a lot of time, but at the same time, preparing for the medium- and long-term future has to happen now. We shouldn't waste any time in seizing opportunities that are here for the taking. So that's the reason why we decided on a departure date, which concretely aligned with the filing of the major universal registration document and the 20-F in the U.S., which was a way to close that chapter and open a new page.

And yes, well, I'm sorry, also, I'll point out that the remuneration that was provided for in his contract was due even if Paul Hudson stayed on for another 3 months. And so he had his term as a director for which he was not remunerated. That's not what triggered his severance package. His severance package was in his CEO contract that was independent, and we simply applied the policy and the rules, and he would have had exactly the same amount if he left today. That didn't change anything if that was the meaning of your question, which I didn't understand at first.

Yes, yes, please, please. You'll have your opportunity. I'll look to the center, the gentleman in blue. Yes, #2, please.

I'm an individual shareholder. I have a question about the share price, which is going through a rough patch, which is not aligned with the 2025 financial results, the 2026 outlook, the financial ratios or the comparison with other pharmaceutical majors.

Very often, it is noted that Sanofi is dependent on Dupixent for its growth and also how weak our R&D portfolio is and so the lack of visibility on replacing Dupixent when Dupixent goes off patent. As you showed in 2030, we'll have EUR 20 billion in revenues generated by Dupixent and EUR 20 billion from the new portfolio.

Have you got any more items about the revenues, especially with the loss of exclusivity of Dupixent?

And the Chairman points out that we're talking billions here, not million. But first, a few points of an answer. Of course, the more successful Dupixent is, the bigger the challenge of an at least partial compensation for that success. But I mean, it's better to have as big a success as Dupixent. It's better to have revenues, to have money to invest and build Sanofi's future beyond 2030 or 2031.

Secondly, I wanted to remind you of something very important, which you didn't mention. The booking of all Dupixent revenues in our accounts is a thing, but don't forget that we developed Dupixent in partnership with another company called Regeneron. And finally, we only book 50% of the profit. So if you're thinking about offsetting that in the future, we need to offset half of the profit and not 100% of revenues. That's a major thing.

And thirdly, the whole challenge, as you said, is to find drugs that will take over to a certain extent. But I wanted to focus on that. The 2025 results are not just due to Dupixent. As Francois highlighted correctly, there are other products like ALTUVIIIO and Beyfortus, which are real success stories for Sanofi that took over from other drugs.

But you're right in saying that we need to keep feeding and strengthening our pipeline to build beyond 2030, 2040 in manageable proportions with a lot of resources to be invested in the next 5 to 6 years. But we'll need to do that wisely, both in terms of in-house spending, our EUR 8.5 billion in annual spending for research and development or mergers and partnerships because we'll have cash flow available for that. That's what we'll do under Belen's leadership.

Yes, I can see a lot of impatience, but you'll have your turns. The gentleman in blue -- yes, I'm sorry. Number five, a gentleman with a pink shirt and then the gentleman with the white shirt will have the floor.

I'm an individual shareholder. I'm sitting back. I love your answer about Mr. Hudson's departure. We won't get back to that, but you made a EUR 3 billion worth acquisition of L'Oreal shares -- of shares sold by L'Oreal at EUR 101.5. Today, the share price is at EUR 78. So if I do a back-of-the-envelope calculation, it seems that you lost EUR 1 billion on the purchases. And if L'Oreal was to sell its remaining shares, would you buy automatically? Does Sanofi get a right of first refusal for these shares held by L'Oreal?

And then on Page 99 of the annual report on the level of remuneration, you compare yourselves to the 12 biggest market caps on the French index and your pharmaceutical peers. But for individual shareholders, I'd like you to compare yourselves to other companies on the French index that are very well rated, especially Air Liquide. Air Liquide is extremely kind to its shareholders because it pays attendance fees to shareholders who attend the AGM.

Is it something that you have thought about? Because when you buy into Sanofi, well, beyond the dropping share price, it seems that we are not very well treated when it comes to the welcome we get. I think that's a minimum.

Well, first of all, sir, I acknowledge the fact that you feel you're not very well treated, but there's the dividend involved in the shareholders' remuneration. And as François Xavier recalled, this is the first year of consecutive growth in the dividend. So let's look at all components of shareholder remuneration. But then regarding the stock market and the share buybacks, there are stock market rules we have to abide by. We can't just be tactical here. So we bought shares from L'Oreal.

And then regarding the share price, that's the -- that's what happens to all companies. You can buy at a certain price, and then it goes another way, but that's what we're going to work on these next few years. We want to bring the share price back up. But we don't have a right of first refusal on shares held by L'Oreal. L'Oreal is still a loyal and truthful long-term shareholder of Sanofi.

The gentleman in White, I'm Mr. B.

I wanted to come back to research, development and innovation. We all understood that it is the key that it's the main engine for a good business model. Here, I remind that a few years ago in this room, the Mr. Elias Zeroni presented some of the consolidated account, who was the global research manager for Sanofi Aventis.

And when I talked to the research team, he was a well-recognized figure with Professor Emeritus at various universities in the U.S., and he was behind the innovation for several compounds. And he brilliantly made a presentation without teleprompter. But now in the Executive Committee and the org chart, I can no longer see such a figure. So I wanted to know whether Mr. Elias was providing any service to the company as a partnership or not, so that Sanofi can continue developing. And I was intrigued that he didn't become a CEO 5 or 6 years ago., we haven't heard of him since

Well, maybe I'll turn to Olivier because I wasn't fortunate enough to know this man, but maybe a general comment. Remember that in this pharmaceutical industry, it's very difficult to have success lasting decades and decades. There are very few pharmaceutical firms who are able to ensure success and develop. So you need to remain very humble in this industry and to fundamentally build the foundation of solid R&D.

And as Olivier said, we started building this foundation years ago. We're not starting from 0. Don't get this idea, but we need to complete building the foundation with new talents, new teams, new modes of governance and therapeutic areas that are sometimes new, our stronger presence in immunology, for instance. So these choices need to be consolidated with determination against a long-term backdrop, and that's going to be our challenge for the future. And I'm very confident about that and Belen's leadership. And she's coming from an R&D background, which is very important. Olivier?

Maybe a couple of comments there. First of all, Elias Deroni played a very important role, especially with our Regeneron colleagues on the design of the clinical trials that helped make Dupixent what Dupixent is today. Secondly, in this industry, it's a very delicate chemistry between getting development products from the outside, especially in early phases 1 and 2 products that are very often developed faster by biotechs being able to integrate them and then develop them.

But on the other side, we also need to be -- well, to have a balanced portfolio management, we need to be able to get products that are more derisked, where value creation is not so high, but that are able to ensure a good balance between products. And so now we have very effective teams working in our therapeutic areas, in excellence areas, vaccines, rare diseases and immunology. We're also working on something that has become stronger with arrival.

We're now working with external advisory boards to make sure that when we assess projects, we assess them in the most balanced way possible to be sure that we don't fall in love with our own products. and suddenly to make sure that we have the best view of what's going on outside the company. So there's internal and external development. So it's very important to have our own projects challenged by outside resources, and this is what we are doing. Well, now let's look to my left. Madam, I can't see your sign #8, please.

I find it difficult to see you because of the reflections.

Individual shareholder, congratulate Belen Garijo for becoming the first woman in Sanofi's history to be appointed CEO. My question relates to the reduction of the mandate of the CEO that went from 6 years to 4 years when you compare with your peers. Usually, you have much longer tenure that are good to create long-term value. I'd like to understand why is it that you've made that choice to shortly reduce the duration of the mandate.

So Madam, thank you for your question. And thank you for congratulating Mrs. Garijo. I'm also very proud to have a woman as a CEO, but there's a difference between an average duration of the mandate and the legal duration. Most Kakahon companies align the duration of the mandate on the mandate on the Board of Directors. That is our first mandate of 4 years as Director and CEO.

Of course, that mandate can or could be renewed. And then it can be 8 years, 12 years, depending on the case. And as for the actual mandate of CEOs in the peer in the industry, it is not that long. There is an acceleration of effective mandate renewal. I agree with you that it's important to be consistent in time. I think that beyond the case of Belen, we're going to end -- finish building the pool of internal talent so that when it is the right moment to take over in the form of strategic continuity. It's also important to have strategic continuity. So we do have that in mind, including for the case of Sanofi.

I'd like to turn to my right. I don't see the number. you're #4. Thank you for your help. When is it that you're going to start the investment in Vitri? You have invested EUR 1 billion. We're really eager, we're still eager to keep investing in. Given the evolution of our pipeline, given the number of recent failures, we're in the process of measuring this revision of the pipeline can have. It means -- it doesn't mean that we will not -- it's always a question of seeing the evolution of the portfolio and the volumes, it's a trade-off, but be convinced that, that does not change our end objective to invest in.

Maybe what will change is the time line given the evolution of our portfolio. More widely today, we have 35% of our industrial headcount in France and 35% of our industrial basis in France, and we are attached to that. But it's been a year that you've been giving those answers. When will that be given the evolution of our portfolio, given a number of events that have taken place, we are confirming our desire to invest in Vitri, a number of projects the arrival of new products have been delayed. So we're going to be working on the impact in 3.

Still question. Yes, the blue, the gentleman with the blue shirt, please.

Mr. M, an individual shareholder. One question regarding all of the OPAs, some French biotechs reach Phases 1 and 2. What are you going to do with those molecules validated by the FDA or Europe? Are you going to invest in them or leave them to your competitors?

Today, we are in the number of therapeutic area, immunology, notably rare disease vaccine and the way in which we appreciate does not depend on the nationality of the biotech and financial elements. In the past, we have made a number of operations with French biotechs. If they have a meaning for us to complement our portfolio, we will keep doing it. Gentlemen, yes, #5. I have a question on IA. First 2 questions about digital IA and cyber.

I think the arrival of Christel will be a very good thing for your company. You have talked about IA. You have said a number of things about IA. It could be interesting to speak with L'Oreal because at the AGM, it was very well explained with practical applications. So that's my question. As NVIDIA does, there is a perception IA, Agentic AI, physical AI, different forms of -- do you have practical applications for those different types of AIs, especially for Agentic AI?

First, you're right to say that Christel and also Barbara Lavernos L'Oreal are very precious directors. That's why we have interesting Board. We count on those directors. Today, the way in which we look into our value chains, a company like ours, we're trying to see where is it that AI is going to create most disruption. Where is it that is going to help us gain in productivity. I have talked about identifying targets more quickly. We are in the regulatory phase. We're in the process of using a number of agents that are going to reduce submission deadlines. In the area of quality, we're increasingly using AI to allow us, for example, to follow the batches.

I remember there were millions of pages allocated to a number of batches. So you realize that today, -- of course, AI is very transformational. Another area in which we think AI is going to have an important impact is from the commercial point of view, having the right interaction, the industry model, which used to be a push model is now being more sophisticated, becoming more sophisticated given the models and the use of agents will allow us to have a better vision of contacts with HCP on sites in order to be more relevant in the way in which we make our commercial investments.

Thank you. Madam. You have the floor. Number one.

Jian, individual shareholder. I wanted to ask you about your decision to invest EUR 20 billion by 2030. I won't ask you about the rationale, but is that commitment going to be limiting the wider options Sanofi could have, in particular with China?

No, I think that I hope we have shown you how Olivier has said it, the need to review our industrial siting or sites to invest everywhere in the world. We've said it for France. You were referring to this investment in Vitri, I'll let Olivier comment. Look at insulin, for example. We're investing both in Frankfurt and in China in order to have more resilient production. So we're investing in a resilient manner.

Regarding the U.S., the announcement we made of EUR 20 billion was made before a number of events that have occurred regarding MFN, the most favored nation. The reasoning that was ours is related to the fragmentation of the world. And in the U.S., until recently, more or less, give and take, we used to manufacture 25% of what was used by U.S. patients.

That's why we have decided to change that. We're going to keep investing in China, given that China is our second market, having a balanced industrial presence in the different geographies, be it Europe, U.S. and China, that's important for us. So our investment strategy is meet is based on a desire to be very balanced in a more fragmented world.

We want to ensure the provision of drugs to our patients.

Time, it's flying, but we're going -- we have time for a few more questions. Number two, Question number 2. Thank you. So, that is your second question.

I'd like to congratulate Mr. Frederic Oudea, who was able to have -- to ask Mrs. to start working on May 1 in France. I don't know there's a formal nature, a formal character to this date. I know it's Labor Day in France. Tongk. More seriously, you've talked about insulin. I think you've put -- you've invested EUR 10 million in, a Lyon company based in Lyon that is working on insulin. I think you asked the same question last year, sir, it's possible.

Let me say one thing. Regarding the obesity drug, things have changed with the arrival of the products manufactured by Lilly and Novo Nordisk. So we have an option to work on type 1 patient with Asia. This option will end in June. This is when we'll be able to tell you more about it. But until now, so it's already -- we've had very rich debate. Thank you very much.

Maybe we can have one last question if there are questions. One question in the middle, the gentleman with a white shirt.

I would have a question regarding employment and the use of AI. What will be the impact on employees of the arrival of AI? Don't you think that you're misleading people when you say we need to invest in R&D, whereas for years, you said you wanted to do away with R&D, including.

Regarding employment, once again, in the last 3 years, we've been reinforcing our investment in R&D. The October of '23 was an increase in expenditures to support innovation in Sanofi. In our future projects are still based on increased expenditure. Management is very clear. But of course, what the lan wants is to make sure that each euro invested is as productive and efficient as possible because there are different ways of spending money. We have to optimize the use of resources regarding the impact on employment. It goes without saying that AI in a way is going to make a number of tasks different if they can be automated. We talked about agents that is going to allow for important gains in productivity.

First of all, it allows each of us to be augmented as we say. With AI, we can solve problems we couldn't solve before. It's going to create a number of jobs that did not exist before. AI allows us to put together data and to draw a number of things with it. with the emergence of a number of functions that did not exist.

So there are productivity gains for some functions with a low added value that will be impacted by AI and a number of functions, new functions that will appear. And in the last few months, we've started thinking about the new jobs that are going to appear. Of course, we need to be able to accompany those technological innovation.

All right. Well, thank you so very much. This was a very fruitful exchange. And now the time has come for the resolutions. And so I'm not going to read out all 21 resolutions -- of course, if there are any questions about the resolutions, we can answer questions before we vote on them. But otherwise, I'll give the floor to Jeanne, who will tell you about the vote on resolutions.

All right. We have more than 851,428,095, which is 71.01% of voting rights. The use of the box -- you will have a presentation on the screen. This is something about using the box. You cannot share it. You have to press the button to say yes, no or don't.

All right then. First resolution, approval of the individual company financial statements for the year ended 31 December 2025. Please vote now. Voting is completed, and we get 99.95% of votes in favor. Number two, approval of the consolidated financial statements for the year 2025. And the resolution gets 99.95% of votes in favor. Number three, appropriation of profits for the year ended 31 December 2025 and declaration of dividend. Please vote now. Resolution is adopted 99.95% of the votes in favor.

Then the next resolution #4 is reappointment of Christophe as Director.

All right then we get 87.5% of votes in favor. Congratulations, Christophe. Resolution #5, reappointment of Jean-Paul as a director. Please vote now. And now we get 99.41% of the votes in favor. Congratulations, Jean-Paul. And #6, appointment of as Director. Please vote now. 98% of the votes in favor. Congratulations to Belen. Number7, appointment of Christel Heydemann as a director. Please vote now. And we get 99.99% of the votes in favor. Congratulations, Christel. Number 8, approval of the report on the compensation of corporate officers issued in accordance with Article L 22-10-9 of the French Commercial Code. Please vote now. And the resolution gets 93.02% of the votes in favor. Number 9, approval of the components of the compensation paid or awarded in respect of the year ended 31 December 2025 to Frederic Oudea, Chairman of the Board.

Please vote now. And the resolution is carried with 98.4% of the votes in favor. And now 10, approval of the components of the compensation paid or awarded in respect of the year ended 31 December 2021 to Paul Hudson, Chief Executive Officer. Please vote now.

[Voting]

And voting is concluded. We get 90.16% in favor.

Now 1, setting of the amount of directors' compensation. Please vote now. Indeed, we get 96.08% in favor. Number 12, approval of the compensation policy for directors. Please vote now. The resolution got 96.39% of votes in favor. Number 13, approval of the compensation policy for the Chairman of the Board of Directors. Please vote now. And indeed, we get 99.02% of votes in favor.

You get #14, approval of the compensation policy for Paul Hudson, Chief Executive Officer until end of day on February 17, 2026. Please vote now.

[Voting]

We got 93.07% of votes in favor. We get to #15, approval of the compensation policy for Olivier Charmeil, Interim Chief Executive Officer. Please vote now. Resolution got 96.41% of votes in favor. You get to #16, approval of the compensation policy to Belen Garijo, future Chief Executive Officer. Please vote now. And the resolution got 92.38% of votes in favor. 17, authorization to the Board of Directors to carry out transactions in the company's shares usable outside the period of a public tender offer. Please vote now.

[Voting]

And we get 99.48% of votes in favor. We move on to resolution #18. This is amendment to the company's Articles of Association. Please vote now.

[Voting]

And the resolution got 97.4% of votes in favor. We get to 19. Delegation to the Board of Directors of competence to decide on the issuance of shares or securities giving access to the company's share capital reserved for members of savings stand with waiver of preemptive rights in their favor. Please vote now.

[Voting]

And the resolution gets 98.64% of votes in favor. We get to 20, and that is the delegation to the Board of Directors of competence to decide on the issuance of shares or securities giving access to the company's share capital to categories of beneficiaries consisting of employees and corporate officers of foreign subsidiaries with waiver of preemptive rights in their favor. Please vote now.

[Voting]

And we get the resolution. Adopted with 99.98% of votes in favor. And then we get to the last resolution, powers to carry out formalities. Please vote now.

[Voting]

And we get 99.98% of votes in favor. Thank you. Well, ladies and gentlemen, we -- all the resolutions were adopted and our agenda is exhausted. Thank you for your trust. Please remember to return your headsets and voting boxes. Next AGM will be 28 April 2027. Thank you.

Hello, everyone. This is Thomas Larsen from the Sanofi IR team. Welcome to the First Quarter 2026 conference call for investors and analysts. As usual, you will find the slides on sanofi.com.

Please turn to Slide #3. Here, we have the usual forward-looking statements. We would like to remind you that information presented in this call contains forward-looking statements, which are subject to substantial risks and uncertainties that may cause actual results to differ materially. We encourage you to read the disclaimer in our slide presentation. In addition, we refer you to our new Form 20-F on file with the U.S. SEC since February in our French Universal Registration Document for a description of these risk factors. As usual, we'll be making comments on our performance using constant exchange rates and other non-IFRS measures. Numbers used are in millions of euros and for the first quarter, unless stated otherwise.

Please turn to Slide #4. First, we have a short presentation, then we'll take your questions. We aim at keeping it all to 1 hour, including the questions. We are mindful that other companies are also reporting today. For the Q&A, we have Manuela and Thomas to cover our global businesses as well as Roy, our General Counsel; and Brendan, Head of Manufacturing and Supply. [Operator Instructions] With that, I'll now hand you over to Olivier, our Interim CEO.

Hello, everyone, and thank you for joining our conference call. As Thomas mentioned, I'm the interim CEO before our new CEO, Belén Garijo, joins Sanofi in May after next week Annual General Meeting. Before we get started, I also want to thank Paul Hudson for his work as CEO from 2019 to 2026 and his work with the management team here at Sanofi.

Now on results, I'm pleased to report that we delivered a strong start in 2026 with double-digit sales growth and earnings growth, reflecting strong performance across our company. Pharma launches performed well, driven by Ayvakit, ALTUVIIIO, and Sarclisa. This exemplifies our ability on the commercial side. Modest vaccine growth was led by our expanded PPH portfolio, which now includes the hepatitis B vaccine, Heplisav-B, following the Dynavax acquisition that closed in February.

Other medicines were impacted by the ongoing divestment of legacy medicines and modest contraction in older medicines in the rest of the world. Dupixent continued its strong performance with continued underlying volume growth across indications and market, while dollar growth was boosted from a lower base of comparison in the U.S. in 2025. Overall, the first quarter demonstrated solid progress across our key growth drivers and sets up well for the remainder of the year with guidance unchanged.

Turning now to Slide 6. Our launches continue to drive strong momentum and represented 14% of total sales. The performance was led by ALTUVIIIO with EUR 325 million in sales, up 42%, followed by Beyfortus with EUR 284 million, reflecting continued global expansion. Sarclisa grew by 30% to EUR 167 million, driven by higher demand in all geographies, reflecting increased use in the frontline setting.

We saw medicines and vaccines from our recent acquisition contribute meaningfully to growth. Ayvakit delivered EUR 170 million and Heplisav-B contributed EUR 46 million since the completion of the Dynavax acquisition. Recently launched Wayrilz, Qfitlia and Myqorzo continued to make progress as we expand access for patients. Overall, our launch portfolio grew by 44% versus last year or approximately 22%, excluding acquisitions. The performance of our launches reflects our continued focus on commercial delivery across the business.

Turning now to Slide 7. Dupixent continued to deliver exceptional sales growth with first quarter sales approaching EUR 4.2 billion. Strong year-over-year growth was driven by continued market penetration across existing and new indications as well as a lower basis of comparison in the U.S. last year. As shared previously, we anticipate volume-driven growth to continue with some normalization in the second half of the year as new launches annualize and comparisons are getting tougher.

Dupixent remains the #1 prescribed biologic medicine across top specialists in the U.S., reflecting the confidence of physicians in Dupixent's efficacy and safety profile. This performance underscores our ability to successfully launch and scale across multiple indications and geographies. With the U.S. approval in February in allergic fungal rhinosinusitis, Dupixent is now approved in 9 indications and reached more than 1.4 million patients.

Moving now to Slide 8, where we outline the multiple options we have in place to sustain value creation for the Dupixent franchise. Let me walk you through each of the 3 pillars. First, Defend. We have a robust patent portfolio of issued patents and pending application with expiration dates running from 2031 to 2045. We have a vigorous defense plan with the expectation to protect Dupixent innovations beyond the U.S. compound patent expiration in March 2031.

Second, Extend. We have the potential to extend Dupixent's dosing interval to every 4 weeks to improve patient convenience. We will pursue this through 2 approaches: a higher dose approach in asthma where development is currently ongoing and a co-formulation approach for which clinical studies are expected to start in the second half of 2026. And third, Innovate. We can potentially pursue new molecules to leverage our existing alliance infrastructure to bring new medicines to patients. Together, these 3 pillars represent multiple complementary options for continued value creation to sustain the long-term durability of the Dupixent franchise.

Turning now to Slide 9. Rare diseases are named rare as they affect relatively few people, fewer than 5 in 10,000 people according to the EU. And in the U.S., rare disease affects fewer than 200,000 people. But collectively, rare disease impact hundreds of millions of individuals worldwide. Many people face years of misdiagnosis and limited treatment options.

Sanofi has built a deep differentiated expertise across rare disease, spanning from lysosomal storage disease, rare blood disorders and more recently, systemic mastocytosis disorders. With this, we now have a very sustainable and competitive business. In Q1, this business reached nearly EUR 1.8 billion, and grew by 20%, led by Ayvakit and ALTUVIIIO. Our growth is fueled by innovation and by new launches, which contribute to almost half of sales. Sanofi's mission in this space is clear, to bring transformative therapies to patients faster and to remain a long-term partner to the rare disease communities we serve.

On Slide 10, vaccine sales reached EUR 1.3 billion in the first quarter, reflecting solid underlying fundamentals. Following the consolidation of Dynavax in February, PPH and booster now include Heplisav-B, which grew by 18% on a market pro forma basis.

Now I want to share some recent headlines. A new study published in the Lancet Infectious Diseases showed for the first time the benefit of Beyfortus in the second season. On top of an 86% reduction in RSV LRTI hospitalization in the first season. It demonstrated a 55% reduction in hospitalization for infants immunized in the first season. This underscores Beyfortus differentiated clinical profile and long-term value for patients.

Additionally, Nuvaxovid, our non-mRNA COVID-19 vaccines continues to differentiate on tolerability as supported by the data presented at ESCMID, a key advantage that could help drive higher COVID immunization rates. In the first quarter, our vaccine business demonstrated resilience and depth. We continue to deliver on our commercial priorities, strengthen our pipeline through disciplined business development and build real-world evidence that supports the long-term value. This gives us confidence in the trajectory ahead.

Before moving to the financials, I'm pleased to highlight Sanofi's 25 years partnership with the WHO to eliminate sleeping sickness, a neglected disease affecting vulnerable population in Africa. Since 201 (sic) [ 2001 ] we have achieved 3 major milestones. In 209 (sic) [ 2009 ] together with partner, we introduced the first effective and safe combined therapy to treat late-stage sleeping sickness. Then we co-developed with DNDI the first oral treatment, which is approved in 2018. These efforts helped reduce new cases by 98% between 201 (sic) [ 2001 ] and 2024.

In February, Acoziborole also co-developed with DNDI, received a positive CHMP opinion. Acoziborole is the first single-dose treatment and requires no hospitalization or lumbar puncture. Due to its simplicity, it can be easily administered in remote village, supporting the WHO goals to eliminate the disease by 2030. Through the Sanofi Foundation, we donate these medicines free of charge to patients. Thank you. And I will now hand over to François, our CFO, for more details on the financials.

Thank you, Olivier, and hello to everyone. Starting with Slide 13. Net sales grew by 13.6% to EUR 10.5 billion in the first quarter. Our growth was supported by 3 main drivers, Dupixent, our recent launches and recent acquisitions as well. On a like-for-like basis, group sales increased by 12%. At constant exchange rates, both gross profit and margins were up, supported by favorable product mix and continued operational efficiencies.

Operating expenses increased by 7%. This was driven by increased SG&A spend due to 2025 BD and M&A activity, including Blueprint and Dynavax as well as some one-off items. As a percentage of sales, OpEx came down by 1.9 percentage points, showing the ongoing impact of our efficiency programs. BOI was up by 10.9% and BOI margin was slightly down due to higher profit sharing and the phasing of capital gains, which were approximately EUR 230 million last year versus only EUR 40 million this year. Our tax rate was in line with the rate of the first quarter of 2025 with a similar additional French corporate income tax contribution in both years. Finally, business EPS grew strongly at 14%, driven by operational leverage.

Turning to our 2026 outlook on Slide 14. We confirm our guidance of high single-digit sales growth at constant exchange rates with business EPS expected to grow slightly faster than sales. Please note that we have a tougher comparison base in H2 with Dupixent's new indication launches and the consolidation of Ayvakit, which started in July 2025. We now expect approximately EUR 400 million of capital gains from divestments in 2026. In March, we signed an agreement to divest Medley, our Brazilian generics business under very favorable market conditions. This incoming disposal will be booked below BOI and is subject to antitrust approvals.

We expect to close this transaction at the earliest around the end of 2026. Profit sharing will continue to grow faster than Dupixent sales and financial expenses are expected to increase this year with higher debt level from BD and M&A activities last year and potentially further deals this year. Finally, I'm pleased to confirm that we will complete our EUR 1 billion share buyback program in the coming days. I will now hand over to Houman for an update on our pipeline.

Thank you, François. The first quarter demonstrated continued momentum across our portfolio. Let me walk you through some of the key highlights. Dupixent received multiple label expansions in the EU for chronic spontaneous urticaria children, in Japan for bullous pemphigoid, and in the U.S. for allergic fungal rhinosinusitis, further advancing our commitment to reach more patients through new indications.

We also obtained EU approval for Rezurock in third-line chronic graft versus host disease, marking an important milestone for patients with limited treatment options. And finally, we are pleased with the U.S. label expansion for Tzield to delay the onset of Stage 3 type 1 diabetes in children as early as 1 year of age that were received just yesterday.

We reported a positive Phase III result for venglustat where the primary endpoint was achieved in type 3 Gaucher's disease, rare disease, while the Phase III study in Fabry's disease did not meet its primary endpoint. We initiated a new Phase III study for frexalimab in kidney transplantation, expanding the CD40 ligand mechanism of action in transplant biology.

On the regulatory front, Wayrilz received orphan designation in Japan for wAIHA and IgG4-related disease, along with breakthrough designation in the U.S. Venglustat was also granted breakthrough therapy in the U.S. for type 3 Gaucher's disease.

After a solid start to the year, now let's explore each of these areas in more detail. Starting with dermatology, where we presented the amlitelimab data at the recent AAD medical meeting. Across all 3 pivotal studies, COAST 1, COAST II and SHORE and across both primary endpoints, IGA and EASI, amlitelimab showed continuous improvement for both every 4- and 12-week dosing schedules versus placebo through week 24 with no evidence of plateau.

There was further -- this was further supported by the ATLANTIS Phase II results through week 52. In addition, itch reduction was similar across both dosing schedules, enabling the potential of very infrequent dosing. On safety, amlitelimab was well tolerated with low rates of conjunctivitis, pyrexia, chills and headache that were observed with other molecules. No cases of Kaposi's sarcoma were observed in these Phase III studies. However, as reported, there was one observed in ATLANTIS, the Phase II study and observed in the ESTUARY Phase III extension study. These cases are both cutaneous in nature, and both patients are recovering after discontinuation of treatment.

In general, overall rates of malignancy were similar to placebo. We look forward to share more data from the ESTUARY Phase III extension study as we approach the regulatory submission anticipated at some point in H2 2026. In atopic dermatitis, we plan to prioritize efforts on amlitelimab and our first STAT6 inhibitor that recently entered Phase I with our partner, Recludix.

Now moving to our respiratory portfolio on Slide 18. We are building a differentiated and innovative pipeline and have made further progress this quarter. We reported top line results of lunsekimig, our anti-IL-13 TSLP bispecific when used on top of background inhaled therapies in 2 distinct key indications. In moderate to severe asthma, the AIRCULES Phase II study demonstrated statistically significant and clinically meaningful reduction in exacerbations regardless of biomarker status over 48 weeks and similarly, a statistically significant and clinically relevant improvement in lung function as measured by pre-bronchodilator FEV1 also at 48 weeks.

The ongoing AIRLYMPUS Phase II study will further expand the use in patients with high-risk asthma and suffering from high exacerbation rates despite symptom control. In inadequately controlled chronic sinusitis -- chronic rhinosinusitis with nasal polyps, the DUET Phase II study of lunsekimig demonstrated statistically significant and clinically meaningful changes also in nasal polyps scores, patient-reported nasal congestion and obstruction and the Lund-Mackay CT score at week 24. Both studies showed acceptable safety profile.

We are pleased with lunsekimig's results in asthma and chronic rhinosinusitis with nasal polyps and look forward to discussing Phase III studies soon. The results are encouraging, and we look forward to lunsekimig's ongoing PERSEPHONE and THESEUS replicated Phase II/III studies in inadequately controlled COPD patients with an eosinophilic phenotype. Recall our December late-stage pipeline review, we made the decision to prioritize medicines to specific indications where the mechanisms may work best. Amlitelimab was deprioritized in asthma to focus resources on the most promising opportunities.

As for itepekimab, the CEREN 1 and 2 Phase III studies in chronic rhinosinusitis with nasal polyps are ongoing with readouts anticipated next year. In COPD, we're in discussions with the regulatory authorities and with our partner, Regeneron, on a potential Phase III study. There is no final decision made yet, and it will be subject to overall portfolio prioritization. Overall, our portfolio is advancing and lunsekimig is emerging as a potentially important medicine across multiple respiratory indications.

Turning now to Slide 19. With the RELIEVE UCCD Phase II study, following fortnightly 900-milligram induction, duvakitug achieved ulcerative colitis clinical remission placebo-adjusted rate of 27% and Crohn's disease endoscopic response placebo adjusted rate of 35%. During monthly maintenance and induction responder patients, duvakitug demonstrated UC clinical remission rates of 58% and CD endoscopic response rates of 55%.

The maintenance response suggests robust sustained efficacy with a convenient monthly subcutaneous dosing. Consistent benefits were observed across clinical endoscopic and patient-reported endpoints and the safety profile was well tolerated and consistent with the induction study. These data support our ongoing Phase III programs and potential life cycle management.

Then on business development, we've added 2 molecules to potential use in chronic versus host disease and other immune indication. Rovadicitinib, a JAK/ROCK inhibitor from Sino Biopharm is already approved in China for first-line myelofibrosis, which fits with our focus on rare blood diseases with an ongoing Phase III study in third-line graft-versus-host disease. Sanofi is responsible for the Phase II development in second line, extending our presence alongside Rezurock.

From Kali Therapeutics, we licensed in the CD19xBCMAxCD3 T-cell engager currently in Phase I in immune-mediated disease with Sanofi responsible for the Phase II development. These additions reflect our focused approach to business development in areas of high unmet medical need within our strategic scope.

Now pivoting to Slide 20 with rare diseases, which remains a core pillar of our strategy with historic presence across lysosomal storage diseases and a deep commitment to our patients. As previously mentioned, venglustat met its primary endpoint in the LEAP2MONO Phase III study in type 3 Gaucher's disease, representing a significant milestone for patients with this debilitating neurological form of the disease and can potentially augment our established medicine, Cerezyme and Cerdelga. It was also designated U.S. breakthrough therapy, which was announced recently.

In Fabry's disease, the PERIDOT Phase III study did not meet its primary endpoint. The CARAT Phase III study is ongoing as we evaluate the path forward in Fabry's. Across acid sphingomyelinase deficiency or Niemann-Pick disease, type 1 mucopolysaccharidosis and Pompe disease, our established portfolio reflects our long-term commitment to that.

On Slide 21, now let me share an update on the key mid- and late-stage pipeline developments by using this slide from our December late-stage pipeline review. Our immunology pipeline has progressed by having delivered most of amlitelimab's Phase III program in AD and by lunsekimig's positive results in asthma and CRS with NP.

In neurology, tolebrutinib is still under review with the EU for SPMS, frexalimab in Phase III for RMS and SPMS and riliprubart in Phase III for CIDP, the latter 2 with data next year. In rare diseases and oncology, Wayrilz is advancing with its life cycle management plan beyond ITP and the designations discussed earlier. Venglustat for GD3 and Sarclisa expanding with a subcutaneous formulation with recent positive EU recommendations. Our vaccines portfolio awaits future data across pneumococcal disease and other opportunities.

Finally, on Slide 22, let me cover the expected '26 and '27 key news flows. For the remainder of this year, we expect the last Phase III for amlitelimab in AD required for regulatory submission. We also anticipate multiple regulatory submissions based on data we already received last and this year as regulatory decisions for medicines and vaccines under review. Next year, we'll get the IIb data for brivekimig in HS, followed by Phase III studies of frexalimab in RMS and riliprubart CIDP.

My sincere thanks to all Sanofi R&D colleagues and more broadly, Sanofi colleagues who share my commitment to advance science in Sanofi, improve our pipeline from research to regulatory approval and create new medicines for patients who need them. With this, I hand back to Olivier for Q&A.

Thank you, Houman. We will now open the call to your questions. [Operator Instructions] Now we will take the first question.

The first question is from James Gordon from Barclays. James?

James Gordon from Barclays. One question was on monthly Dupixent. I've seen clinical studies to start in H2. But can you clarify what are you going to co-formulate Dupi within AD? And what would the development pathway and time lines look like? And when could this come to market? And would it be quicker for asthma versus AD? That's the first question, please.

And then the second question would be for lunsekimig. So the Phase II headlines look very encouraging, so your TSLP IL-13 in asthma. But are you confident you've demonstrated a materially stronger profile than existing TSLP monotherapies such as Tezspire already on the market? Would you develop this against -- like with the study against Tezspire or just against placebo? So is this a much better product or really just another TSLP?

Yes. So maybe, James, thank you for your question. And maybe we start by the first question on Dupixent AD, Manuela.

Yes. So I would ask Houman also to complement here. So first of all, your question was on the LCM profile of Dupixent. And we are evaluating strategic options, a broad set of strategic options as Olivier reiterated in his remarks, one is on IP. The other part is on formulations. Houman will talk a little bit about the formulations. But there are broader options for Dupixent that we're looking at and that we're considering, including co-formulation, including higher doses with the Q4W dosing to basically provide more options for patients and also elevate and enhance the patient experience. Houman, maybe over to you.

Yes, Manuela, thank you for that. Very quickly, James, I think just to be super clear, with a high dose weight going into asthma, the development plan for that will be relatively conventional, and we'll give you more details of that alongside our partner, Regeneron, going forward. Importantly, with the formulation, we anticipate going relatively broadly. The formulation has been well worked out and we'll be germane and pertinent to many relevant atopic -- I'm sorry, Dupixent indications. The clinical development of those are just being worked out.

On the second question related to the lunsekimig Phase II result, differentiated product, Houman?

Yes. So again, stated rather simply, we're enthusiastic by the results, as I've just called out, in severe asthma and CRS with NP, both of which are strongly type 2 disorders, and we've been excited by the results we've seen, albeit recognizing that this is -- these are early studies, Phase IIb studies.

Just to be very specific, as you asked the specific asthma study, I'll make 3 points. Number one is we comfortably hit our primary endpoint, both statistically and clinically in all comers as anticipated. Number two, speaking to differentiation, as called out, on FEV1 and PROs, we were specifically differentiated. Number three, further details of differentiation in the overall population and in the relevant subgroups will be presented at a medical meeting in a relatively near future. I just want to caveat that while we are excited about lunsekimig in the trial of codependent diseases of asthma, COPD and CRS with NP, we remain thoughtful about how we go forward with these diseases as this was a relatively early study, but it does provide a foundation for our role in respiratory disease.

Next question.

Next question is from Florent Cespedes from ODDO. Florent?

Florent Cespedes from ODDO BHF. So 2 quick ones. First, on Dupixent. In Q1, the drug was less impacted by pricing pressure in the U.S. Maybe could you give us more color on why this happened? And how do you see the next discussions with the payers? And my second question is to follow up on lunsekimig. Just I would just like to know if you will wait for the Phase II results on the high-risk asthma next year before taking a decision to launch a Phase III program or if you could decide in the near future for the next step for lunsekimig?

So first question, Manuela, on price pressure on Q1.

Thank you, Florent. So first of all, we're very pleased with Dupixent's continued strong performance, the 31% of growth that we have shown in Q1, which is largely driven by underlying demand -- strong underlying demand across established indications, but also driven by strong uptake in recent launches.

As you rightly pointed out, the Q1 performance partly reflects a low basis of comparison due to higher gross to net price adjustments in Q1 2025. But again, if you correct for that, the sales growth is largely driven by volume demand. You know that GTN fluctuates from quarter-to-quarter due to many different factors. Q1 in the U.S. usually is highest because of the annual insurance benefit resetting. But to your question on payer pressure, we have a robust GTN strategy in place, which we continuously evolve to ensure long-term profitable growth while maintaining a favorable patient access for Dupixent in general. One thing to note, though, we expect the strong demand growth to continue. But at the same time, we will -- we expect some moderation in the second half of the year as recent launches will annualize.

So going to the question on lunsekimig and the development strategy.

Yes, very straightforwardly, 2 bullet points. Number one is we do not anticipate waiting for the AIRLYMPUS results before we move forward. Number two is progression to Phase III will solely be subject to, obviously, internal portfolio decision-making, but currently a regulatory conversation.

Next question is from Luisa Hector from Berenberg. Luisa?

I wanted to follow up on the longer-acting Dupixent, please. Could you comment on the actual technology? Is this with a partner? Are there additional payaways? And can we assume the financials with Regeneron remain the same? And perhaps just a question, could you stretch it even longer than every 4 weeks?

And then second question, Olivier, great to have you on the call. So thank you. We've had you just for a few weeks as Interim CEO, but obviously, you have an impressive amount of experience at Sanofi and you've made a contribution to the significant transformation over the past 5 years. So the question for you is what advice might you give to Belén when she arrives in a week or so?

So on the first question related to the longer-acting Dupixent, I give it to Houman.

Yes, I'll be short because we want to hear Olivier's response. Luisa, thank you for your thoughtful question. Yes, the technology is pretty straightforward. It is with a partner. It is precedented, and we see it being used in -- across the -- majority of Dupixent indications. Olivier?

So on the -- thank you for your question, Luisa. First, I'm very happy to work again with of course, Belén, with whom I have worked in the past, and I know pretty well. I would be very cautious in the advice that I would give her. But the first one is to take some time to make the right diagnostic. I think the company has considerably changed in the last 5 to 10 years. The way the company has modernized is, of course, very impressive.

I think in the last few years, a lot of -- we have gained a lot in terms of better prioritization, internalization of the company. We have also significantly increased our capabilities, notably in the U.S. in terms of marketing and commercial. Of course, it's going to be a period after the diagnostic where she needs, of course, to be decisive and knowing her, I know that she will make the right choices. She will examine, of course, and review the portfolio. I can tell you that in order that she gets prepared, I have prepared with my team a solid program so that she can, when she joins early May, be up and running from day 1 and clearly work on the topics that really matter for the future of Sanofi.

Next question is from Steve Scala from TD Cowen. Steve?

I am just curious why a year ago, Sanofi wouldn't speak to Dupixent LOE extension, but now includes slides in the deck. It seems that there are 4 possible reasons for this change. The first is that Sanofi now has more confidence, and I'm wondering why. Second, the outlook for the pipeline assets expected to form the next generation is unclear. Third, the LOE is near. Or fourth, a change in communication strategy may be related to the CEO change. In the absence of any other information, I think we have to assume it's the pipeline. I'm wondering if you would push back on that.

So we can start maybe on the question that is related strictly to the LOE with our General Counsel.

Thanks for the question. We've always been consistently saying that we have a very strong patent portfolio and that we intend to vigorously defend Dupixent and that we expect it to go beyond the compound calendar year, which is March 31. I think you see it on the slide for the first time because you see some other things there regarding the future of the alliance, and it was just put in writing. We had the same question last quarter, and I answered it. François, on the slide maybe...

Yes. No, Steve, I think that, anyway, there is a logic that we talk about it because we get nearer to the LOE. And we see that there is a very strong appetite from the investor community to understand what's coming after the LOE of Dupixent. It's a major product for us. So I think we see that there is an interest, and we need to answer to the investor community. This has been done, by the way, perfectly aligned with our partner as well, Regeneron met some communication about it as well at JPMorgan. So there is a logic that we talk about it as well. So I don't think there is any defensive view on that matter.

Yes. And the last point, Steve, and thank you for your question, it has nothing to do with the change of CEO. Paul took the commitment in H1 to make an update on the Dupixent LOE.

Next question is from Sachin Jain from BofA .

Just another one on the Dupi extension slide, if I may. So I wonder if you could just provide a bit more detail on the right-hand Dupi innovation column and where you are with other assets being discussed within the alliance of the IL-4 receptor and then level of progress on discussions around whether each party would put other assets into the collaboration and when we might hear on that?

And then I just wanted to go back to a prior question. There was a question on the Q4 week Dupi and whether you could extend beyond that. I wonder if you could just address that. Just wondering whether Q4 week is enough of an extension relative to existing given the competitive landscape by the time you launch it.

So Houman, you take the two questions. Maybe you start by the Q4 week extension.

Yes, Sachin, thanks for that. We'll answer to the question. At the moment, we're very focused around the Q4, and we are confident that the Q4 -- let's just take a step back, 1.4 million patients are dosed with Dupi. It is the immunology molecule of the EPOC. Moving to Q4 is an engineering innovation that we -- that will serve patients. So number one is, at the moment, we're focused on the Q4 and providing that in multiple indications, et cetera.

And then we'll move forward on any further innovations. And you wouldn't expect us at this point to show our hand too much on those further innovations. And to question one, we work very closely along the alliance, specifically with the teams in George and Len on those various, I think you call them right-hand column indications, whether it's super Dupi or other molecules that we've talked about and those molecules are being progressed together. Certainly, those are in the alliance. And we're excited about moving those forward. We'll tell you more about those over the next few years.

Next question is from Richard Vosser from JPMorgan. Richard?

A couple of questions, please. Firstly, just on amlitelimab, I wondered if you could give us a bit of color from feedback on physicians from AAD around the data you presented and in particular, the Kaposi's sarcoma events. any concerns you're hearing from physicians around use of amlitelimab because of those events? And then a second question also on the pipeline. You mentioned an outstanding Phase III decision on itepekimab. We've seen another IL-33 from a competitor have a couple of positive Phase IIIs or maybe 3 Phase III trials positive. Just what sort of impact does that have on your thinking around pursuing a further trial given the time required to do such a trial?

Houman, maybe start by the last question on itepekimab before moving to amlitelimab. And maybe Manuela, you take the question.

Perfect. On number one, listen, we are -- as you say, there's an outstanding question about the IL-33, itepekimab molecule. We are in the midst of a regulatory discussion and discussions with our partners, and we will come forward relatively soon, I guess, with a decision, which will be a portfolio decision. Importantly, we take into account all the data, both in the private and public domain regarding molecules that target the same pathway.

And let me -- why don't I just pick up the amlitelimab on as well, Manuela as long as you're happy for me just to do that while I've got the microphone. With respect to amlitelimab, we -- out of an abundance of desire to demonstrate the manifest benefit risk of this molecule, we presented the data at AAD super clearly. Let me be clear on 3 things. AAD still represents an area which is substantially biologic underpenetrated with significant heterogeneity in disease, and there are opportunities for novel mechanisms of action, point number one, the efficacy has been laid out. I won't repeat it, but COAST 1, COAST 2, SHORE.

And ATLANTIS have been extent and showed that there is no plateau effect at 24 weeks. And with ATLANTIS, there's an improvement up to 52 weeks. And thirdly, we've now put as much safety data in blinded and unblinded data that we've got in the public domain up to 4,500 patients approximately, and we remain confident in the benefit risk ratio of this molecule. You asked a question, and I'll be very succinct about physician and other responses. We've seen no impact on enthusiasm of physicians and payers, particularly physicians and patients for this drug based on the data we presented at AAD.

Next question is from Sarita Kapila from Morgan Stanley. Sarita?

So you talked about extending the Dupi LOE beyond March 31. Which patents are you most confident in for extension? So is it the method of treatment patents, so potentially extending exclusivity to 2034. And then the second question was on riliprubart. Could you help us understand what's driven the 1 or 2 delays to the readout? One of your competitors has alluded to recruitment issues given the trial design and the lack of a Part A component. So I was wondering if you could give us some more color, please.

Okay. Maybe we start by the question related to Dupi patents.

Thanks a lot. Picking one patent out of tens of patents is not a good testament to the amount of innovation we've done for Dupixent over the years. We have multiple strong patents going up to 2045. We believe we have a very strong patent portfolio and intend to seriously defend all of them.

So now moving to riliprubart recruitment.

Yes, very quickly. Really had a great set of Phase II results in both patients with standard of care responsive and nonresponsive. We moved straight to Phase III. I think we've learned as we initiated those Phase IIIs, what works best and what doesn't work best, particularly at the screening stage of those studies, and I'm pleased to say that the recruitment is picking up. So as you articulated, we needed to learn something from the screening of those patients, and now we're moving on. We are optimistic about the impact riliprubart can have on patient outcomes based on the totality of the data in the public domain.

Next question is from Seamus Fernandez from Guggenheim. Seamus?

So first on the patent side, just hoping to get a little bit more clarity on how we should be thinking about the timing of potential resolution of the result. Typically, we see something like a major series of settlements 2 to 3 years before. Can you say that you're proactively working on that kind of an outcome to happen sooner rather than later? Or should we anticipate a standard extended process in the courts, particularly in the U.S.?

And then the second question is, really, can you just update us on -- I believe you were studying lunsekimig in atopic dermatitis. Hoping to get a better understanding of where or when we're likely to see those data and if the data there happens to be something that you remain encouraged by or if you're likely to move on?

Maybe we start my second question. Seamus, thank you for question. The lunsekimig AD, Houman.

Yes. Thanks for the question. We've been delighted by the lunsekimig results in, as I said, the triad of the respiratory disorders and our focus is in respiratory disease at the moment. We will make a decision on atopic dermatitis at a later point, but our priority is respiratory disease.

Now moving to the question related to Dupixent patent.

Yes. Thanks. I'm sure you are experienced in following how other drugs have evolved over time. Reminder that this is a biologic. You're asking me about settlements, and we are sitting here with a patent of 50-plus patents in the U.S., none of which have yet been challenged. So if and if we wanted to give clarity to our investors of the strength and even if we have people lining up to discuss. There is nobody at the moment because nobody has challenged our patents. Typically, this happens closer for biologics. This happens closer to launch. We do intend to vigorously defend all these patents to the extent we feel at some point that people understand the strength of our case, and we want to give people clarity, we will do that, but we are quite away before that because we have not been challenged at this stage.

Next question is from Graham Parry from Citi. Graham?

So just going back to the Q4 weekly Dupixent. Can you just confirm if it's hyaluronidase co-formulation, who the partner is and what commercial payways you might have on that? And what formulation studies have been completed to date? And if there's any public data or if you intend to share any public data on that? And then if there is more IP extension you think the co-formulated Q4 weekly might they give you on the asset overall?

And then secondly, on the IL-4 receptor alpha, what are the milestones for that in terms of data points? And what would be the threshold for a decision for the collaboration to invest fully in that project going forward because -- given it's already covered by the collaboration.

Okay. So Houman, on the first question on the Q4 formulation.

Yes, I can confirm that it is hyaluronidase with a partner. We won't disclose any more than that at this stage. And then on the second question, we don't disclose the milestones for internal decisions around the IL-4 receptor alpha.

On the Q4 new patents, any...

Protect every innovation. I think the objective here is patient convenience, and we'll see what that means.

Next question is from Peter Verdult from BNP Paribas Exane. Peter?

Peter Verdult, BNP. Two questions, please, one on the pipeline, one on capital allocation. I'm sorry to labor the point, but going back to the itepekimab question. What are the exact go-forward plans? Because it seems to be dragging somewhat. I think we all thought that AERIFY would have begun quite a number of months ago. So can you just clarify when, in fact, AERIFY might begin in recruitment? Or does the developments across the pond or across the channel at Astra sort of change your thinking about the commercial potential here?

And then on capital allocation, just for Olivier or François, is EUR 10 billion to EUR 15 billion is the right characterization of Sanofi's firepower for BD given you want to maintain a AA rating. And given your comments and you're clearly signaling that you're doubling down on rare diseases, is this the area where we should expect future BD?

Houman, first question on itepekimab.

So I just want to make sure that I was clear on the last question on the IL4 receptor alpha point. I just want to be clear that while we don't disclose the exact stage gates and milestones within the nature of the alliance, it is within the alliance, and we are moving forward with it. So that will -- we will tell you more about that as we go forward.

Pete, to your question about itepekimab, there's no slight of hand on itepekimab. We have to get regulatory approval before -- and a regulatory opinion before we move forward. We have to align with our partner, Regeneron. I'd like to reassure everybody that it's high on our dashboard, Manuela and I on this side of the alliance are partnered, and we will come back to you as soon as we can. As I said earlier, we're taking the totality of data, not just AstraZeneca's data is one, but there's a number of IL-33 data points that we need to take into account before we move forward with COPD.

François, do you want to take the question on BD, M&A?

So on capital allocation, I said last time when we discussed our full year disclosure that we could invest up to EUR 15 billion this year and retain our AA rating in BD and M&A. By the way, it depends on what we buy. Because if we buy commercialized asset, it would go probably even maybe potentially up to EUR 10 billion more. If we were only buying Phase I, Phase II assets, it would be probably significantly less than that because it would weigh on our BOI.

So we are looking at opportunities anyway. Time flies. So as soon as we get 1 quarter, the amount increases to a certain extent as well because we generate additional cash flow and we have a strong growth profile as well, given that we grew double digit. In terms of areas and therapeutic areas, exactly as we did last year. You could see that last year, we invested in 3 of our 4 main therapeutic areas, namely immunology, rare disease and vaccines. So we are targeting as a priority, I would say, the same 3 therapeutic areas, while we don't eliminate either the possibility to invest in white spaces as we did as well last year, for example.

Next question.

Yes. The next question is from David Risinger from Leerink. David?

Can you hear me?

Yes.

I just have one. So François, can you discuss the quarterly EPS progression ahead, including the impact of the Dupixent alliance R&D reimbursement step down?

Are you talking about Q1 or for the full year?

Looking out to later in the year when the reimbursement is eliminated.

Okay. So you know that we are coming to the end of the R&D reimbursement from Regeneron. We will have a negative impact on BOI of probably a good EUR 400 million this year. We expected initially to have another negative impact of EUR 800 million next year, which will be a bit less because we are anticipating. This is partly linked to the fact that since Dupixent is growing faster than we expected, we are anticipating a bit faster the end of the reimbursement. So probably net around EUR 400 million negative impact BOI this year and maybe EUR 700 million next year negative again on the top of what we get this year.

It may accelerate a bit depending on what we do this year with Dupixent, but that's what is likely to happen. We expect the balance to be fully reimbursed around Q2 2026. But obviously, this is the reason why it will have an impact on up to Q2 2027. You may remember as well that we said that in spite of that, our BOI will increase both in margin and in absolute value, both in '26 and '27. So we'll be able to absorb it through our growth profile and profitable growth as well.

Next question.

Yes. Next question is from Matthew Weston from UBS. Matthew?

Took forever to get the signal. Two questions, please. First, in your opening comments, you said was you were concerned over the Kaposi's sarcoma cases because the rates of malignancy faced in the control arm. Kirin observed exactly the same, but said that sarcoma being mechanistic was a reason to kill the program. Why is you right and Kirin wrong?

And then secondly, on Blueprint, a key element of Blueprint acquisition, as I recall, was as a foundation of Sanofi's stand-alone immunology commercial efforts beyond Dupi. Now there's a lot of talk about reinventing the original alliance, that mean you're deemphasizing investment in stand-alone immunology.

So the line was pretty bad. So maybe on the first question on Amli.

Yes. Matthew, thank you for your question. I'm not -- I wouldn't speculate on the decision-making within Kyowa Kirin and Amgen. From our own perspective, all I can tell you is that the benefit risk of amlitelimab is differentiated. We are consistently with the opinion that we bring that to patients. Just to be very specific, our rates of fevers, chills and pyrexia are extremely low and lower than any other molecule in the OX40 pathway.

Number two is that we've, as I said, about 4,500 patients in blind and unblinded studies demonstrated 2 cases of Kaposi's, both of which were cutaneous, both of which are improving. And then number three is across our other side effects and other issues, they're balanced across placebo and treatment arm. So overall, we remain confident at present around the value of amlitelimab in patients with -- the benefit-risk patients with atopic dermatitis. Olivier, over to you.

Yes. So Blueprint has several dimensions. There is an immunology dimension, but there is also a rare disease dimension. And this is why we have positioned it in our rare disease franchise because we think that it's the best home for Blueprint. Next question.

So the next question is from Michael Leuchten from Jefferies who wrote the question. So on Slide 8, you talk about innovation, new assets and new assets to leverage the GV infrastructure. Can you clarify how that links with BD and how you would work with both parties having an economic stake? And then the second one is for François, is BD on pause until Belén arrives? Or is capital deployment in flight or on an ongoing strategy?

We want to start by the first question. I think we have been pretty active, including in the last few weeks on the BD side, but you might want to complement.

No. But I mean, obviously, we are looking forward to welcoming Belén in a few days, but business goes on in the meantime. So we have not stopped working. We have not stopped being active in the market, including in BD. So as Olivier said, we have been very active. And we have an acting CEO as well with Olivier. We have the Board of Directors and the entire management is totally mobilized to continue business while waiting for Belén's arrival in a couple of days.

On -- Michael, on your question regarding any potential joint venture, I would say that, of course, everything is subject to discussion with Regeneron.

So the next question is from Simon Baker from Redburn. Simon?

Two quick ones, if I may, please. Going back to Florent's question right at the beginning. We get a lot of debate now about the competitive landscape within immunology. I just wondering if you could give us a little more detail on an indication-by-indication basis, how you're seeing that evolve. Overall, clearly, Dupixent is outpacing our expectations, but any color on that would be very helpful.

And then a quick one for François. On net financial expense, you did guide for the full year being a little higher than last year because of higher debt. In Q1, it was a lot lower than we were expecting. So I was just wondering if you could give us some pointers on the evolution and cadence of net financial expenses as the year goes on.

Simon, very -- thank you for the question. So François, a little bit more color on the financial expenses.

On net financial expenses, you probably remember that anyway, last year, Q1 was before we received the proceeds from Opella. So we had a rather still relatively high level of net and gross debt, which is the reason why we had a level of finance cost that was relatively high. We gave a guidance at the beginning of the year on the fact that our finance costs would increase this year, that -- and we mentioned immediately that would be subject to additional BD and M&A. We have not been -- we have not bought large assets in Q1, so -- which is the reason why there was no impact in Q1.

So it may, BD and M&A for more significant amounts, if any, if any, I insist, may come a bit later in the year than maybe what we were anticipating when we were doing our budget. So you can probably factor the fact that there might be a little bit less than what we thought initially for the full year. That being said, I still expect an increase in terms of financing costs versus last year, but maybe a bit more moderate than we thought due to some time delay in BD and M&A.

Manuela, on the broad question on immunology.

Yes. And I'll keep it short because we're almost at time. I think the question is a really good one, more competition in immunology. But at the same time, you also have to look at how nascent some of these therapeutic areas still are. Let's just take atopic dermatitis as an example, we're barely above 18% advanced therapy penetration. And new entrants and new mechanisms of actions in all of these categories, more competitors, more players is actually helping to create more awareness and more adoption of advanced treatments. So that's what we're looking for. And there's definitely in all of those spaces, there's still significant unmet needs that we're trying to meet ourselves, but also with additional MOAs. So yes, more competition, but we're actually welcoming it.

Next question is from Rajesh Kumar from HSBC. Rajesh?

Just a bit of clarification on capital deployment strategy. You indicated that if you were to buy a late-stage asset, the firepower could be greater than EUR 15 billion. Are you thinking of buying a late-stage asset? That's the first question.

Second question I have is, obviously, Dupixent, you are going to work on life cycle management. Itepekimab, we don't know what you're going to do. You're dependent on what the regulators are saying. Amlitelimab, you are a lot more confident than others. So if I take all of those, how are you thinking the R&D investments in these projects are factored into your capital allocation framework? Truly appreciate what sort of risk weighting you put to these different scenario outcomes.

So Rajesh, thank you. On the first question on late-stage asset related to capital allocation.

Yes. Rajesh, I cannot comment on what we are looking at today because it's obviously confidential by nature. But we -- I think we have a duty to look broadly at the asset that makes sense from a strategic point of view, from a scientific point of view, from a financial point of view. So we are looking at a certain number of assets, including late-stage assets, although speaking, we have said it over the last couple of quarters, our interest is more for early-stage assets. But we are not eliminating or discounting any opportunity either in late-stage assets.

As I said, if we were buying late-stage assets, as for example, or commercialized assets as we did with Blueprint last year, obviously, it adds some BOI. And as a consequence of that, it does give us a little bit more opportunity in terms of leverage. But -- so we -- once again, we are looking at a fairly broad spectrum of assets as we always do, and I think we have a duty to do that.

Rajesh, maybe getting back to your second question, can you be a little bit more precise with your question on Dupixent life cycle management and allocation of resources?

Basically, you're going to -- sorry, you're going to do some development expenditures there, right, for different formulations, and you're going to come up with a strategy to manage the life cycle. So you're going to spend money on R&D, right? So how much of that was already factored into your earlier medium-term R&D spending run rate? And how much is incremental and new?

So Houman, how much is incremental or how much is already factored in our plan?

Yes. Much of it is factored in. And of course, it's part of the alliance relationship with Dupixent. And so that's pretty straightforward. Thanks, Rajesh, for the question.

Okay. So thank you, Rajesh, for this last question. So we had a very strong start to 2026 with double-digit sales and EPS growth. Sales advanced by 13.6%, supported by pharma launches and recent acquisition and business EPS was up by 14%. We obtained 5 regulatory approvals, all in immunology, achieved 1 positive Phase III study readout for venglustat in rare disease and reported encouraging Phase II data for lunsekimig in respiratory disease. And finally, we reiterate our guidance for 2026 and the commitment to deliver profitable growth. With this, I would like to thank you for the interest in Sanofi, and we will now close the call.

I will now close the session. Everybody, have a great day.

Hello, everyone, this Thomas Kudsk Larsen from the Sanofi IR team. Welcome to the Q4 and Full Year 2025 Conference Call for investors and analysts. As usual, you can find slides on sanofi.com.

Please turn to Slide #3. Here, we have the usual forward-looking statements. We would like to remind you that information presented in this call contains forward-looking statements, which are subject to substantial risks and uncertainties that may cause actual results to differ materially. We encourage you to read the disclaimer in our slide presentation.

In addition, we refer you to our Form 20-F on file with the U.S. SEC and our French Universal Registration Document for a description of these risk factors. As usual, we'll be making comments on our performance using constant exchange rates and other non-IFRS measures. Numbers used are in millions of euros and for Q4 or full year 2025 unless stated otherwise.

Please turn to Slide #4. First, we have a presentation, which is a little longer due to full year results, then we will take your questions. We aim at keeping it all to 1 hour, perhaps a little bit more, including questions. We appreciate other companies are also reporting today.

For the Q&A, we have Olivier, Brian and Thomas to cover our global businesses as well as Roy, our General Counsel; and Brendan, Head of Manufacturing and Supply. [Operator Instructions]

With all of this, I'll now hand you over to Paul.

Well, thank you, and hello, everyone. In 2025, we continued to develop into an R&D-driven, AI-powered biopharma company. Our strategic progress was supported by the completion of the Opella transaction, allowing us to reinvest proceeds into business development and M&A opportunities while completing our EUR 5 billion share buyback program.

We delivered strong performance with 9.9% sales growth and new launches reached EUR 5.7 billion in sales. We're pleased to have achieved another blockbuster milestone last year, ALTUVIIIO. We successfully launched 2 new medicines, Qfitlia for hemophilia and Wayrilz for ITP and one vaccine, Nuvaxovid to protect against COVID-19.

We also achieved several positive Phase III results, including most of the amlitelimab program in AD and the SARCLISA, a subcutaneous formulation. Our innovation engine continues to make progress, replenishing Phase I, including 3 promising gene therapies, our entry into ophthalmology.

Looking at Q4 performance on Slide 6, we delivered very strong results with EUR 11.3 billion in sales and 13.3% growth, supported, of course, by our key drivers.

Turning to our launches on Slide 7. I'm pleased to report that our newly launched medicines and vaccines grew 34% in 2025. Beyfortus continued to deliver with EUR 1.8 billion in full year sales, demonstrating the critical need for RSV protection. ALTUVIIIO achieved blockbuster status, reaching EUR 1.2 billion in full year sales. Patient adoption continues to increase, with patients switching from both factor and nonfactor medicines.

Of note, AYVAKIT reached $725 million in annual pro forma sales, slightly ahead of Blueprint's expectations from early 2025. Our newly launched medicines and vaccines demonstrate our commitment to innovation and the strength of our commercial organization.

Moving to Slide 8. Dupixent reached EUR 4.2 billion in the quarter and EUR 15.7 billion in annual sales. Continued growth across anchor indications and expansion into COPD, CSU and BP drove a more than 30% increase in patients over the past year. This underscores Dupixent's standing as the #1 prescribed biologic across dermatologists, pulmonologists, allergists and ear, nose and throat specialists. The U.S. regulatory acceptance for the allergic fungal rhinosinusitis indication in November brings us closer to a potential ninth indication, further expanding Dupixent's reach.

Turning to vaccines. We maintain our leadership in influenza and RSV despite a challenging environment. Full year sales reached EUR 7.9 billion. In influenza, we gained U.S. market share with the Fluzone High-Dose and Flublok, while Europe saw continued penetration of Efluelda and Supemtek.

Beyfortus delivered a strong performance, growing 9.5% to EUR 1.8 billion, ahead of our anticipated modest growth and driven by geographic expansion across Europe and the rest of the world. With real-world evidence confirming 87% to 98% effectiveness, Beyfortus has protected more than 11 million babies in more than 45 countries, thus preventing an estimated 200,000 hospitalizations to date.

We continue to strengthen our vaccines portfolio with strategic acquisitions that enhance our ability to protect older adults from serious diseases. In December, we completed the acquisition of Vicebio, adding a bivalent RSV plus human metapneumovirus vaccine candidate to our pipeline. This program complements our existing RSV franchise and leverages the innovative molecular clamp technology for vaccine antigen design.

We also announced our proposed acquisition of Dynavax Technologies Corporation, which we expect to close in the first quarter this year. This acquisition adds HEPLISAV-B to our portfolio, the leading adult hepatitis B vaccine in the U.S. with a differentiated and convenient 2-dose schedule. It also brings a shingles vaccine candidate currently in Phase I/II studies, further expanding our pipeline in vaccines for older adults. These strategic additions reinforce our commitment to innovation in vaccines.

Before moving to financials, I'm pleased to highlight Sanofi's key role in developing publicly available specification 2090 or PAS 2090, the first industry-wide global standard for measuring and reducing environmental impact of medicines and vaccines across their life cycle, recently published, by the way, in the British Standards Institution.

We codeveloped this harmonized framework with industry to enable ecodesign for footprint reduction, accurate environmental reporting while addressing growing stakeholder demands for transparency. PAS 2090 marks an important moment for sustainable health care, showcasing how collaboration across the health care system can drive meaningful progress. True patient care means protecting not just individual health, but also planet health. The standard helps us to do both.

Thank you. I'll now hand over to François, our CFO, for more details on the financials.

Thank you, Paul, and hello to everyone. Next slide, please. I'm pleased to report that we achieved our strongest quarterly sales growth in Q4 2025. Net sales grew by 13.3% to EUR 11.3 billion. Dupixent delivered double-digit growth with continued penetration across all indications. Dupixent also benefited from a favorable basis of comparison due to gross to net price adjustments in the previous year. Business EPS growth was strong at 26.7%, reflecting our disciplined execution on operational leverage.

Slide 14, please. Over the past 3 years, volume growth has accelerated and reached 34% on a compounded basis. Growth was driven by our successful launches and by Dupixent expansion across multiple indications, which continues to drive significant volume uptake 8 years after the launch.

Our ability to expand market reach while growing our margins demonstrate the strength of our innovation and our strong commercial execution. To meet growing patient demand and deliver on our MFN commitment, we will continue investing in manufacturing capacity with a strategic focus on the U.S.

Next slide, please. Our full year 2025 results showcase the power of our business model, delivering strong growth with increased profitability. Sales reached EUR 43.6 billion, representing 9.9% growth at constant exchange rates at the upper end of our guidance. This represents a higher underlying growth level than in 2024, given that we excluded hyperinflation impacts from our sales growth at the beginning of 2025.

Business gross margin expanded by 1.8 percentage points to 77.5%, driven by favorable product mix and operational efficiencies. Operating expenses increased by 7.9% as we increased R&D investments and supported our new product launches through sales and marketing investments.

OpEx has decreased as a percentage of sales to 39.9%, thanks to our efficiency programs. Business operating income increased by 11.9%, with BOI margin reaching 27.8%. Business EPS, excluding share buyback, grew by 12.2%, in line with our guidance. And including share buyback, our business EPS grew by 15%. This demonstrates our ability to grow EPS faster than sales while investing in future growth.

Moving to Slide 16. Our free cash flow has returned to strong levels in 2025 at EUR 8.1 billion, representing 18.5% of sales. We aim to sustainably reach free cash flow of at least 20% of net sales in the medium term. This strong cash flow generation illustrates the quality of our earnings and the effectiveness of our working capital management. A key contributor to this performance was our inventory optimization as we reduced inventory by nearly 30 days. We are targeting a similar inventory reduction in 2026, which will help us to progress toward our 20% free cash flow target. This disciplined approach provides us with significant financial flexibility to execute our capital allocation strategy.

Next slide, please. We ended 2025 with a strong capital structure, as highlighted by our low net debt, which increased slightly to EUR 11 billion. We maintained a conservative 0.8x net debt-to-EBITDA ratio. This conservative leverage provides flexibility for future external growth opportunities even while maintaining our AA rating.

We successfully deployed the EUR 10.4 billion received from the Opella divestment into value-creating business development and M&A opportunities such as Blueprint, Vicebio, Dren Bio DR-0201, Vigil and some others as well. These divestments and acquisitions allowed us to accelerate our transformation as a biopharma company.

Moving to the next slide. In 2025, we executed our capital allocation strategy across all 4 priorities. We significantly increased our organic growth investments in R&D, commercial capabilities, CapEx and digital transformation. These investments fuel both current and future growth.

As I just mentioned, we deployed the Opella proceeds into strategic acquisitions. We proposed to increase our dividend for the 31st consecutive year to EUR 4.12, up by 5% from the previous year. Finally, we completed our EUR 5 billion share buyback program. We will pursue our capital allocation policy in 2026.

Regarding share buybacks, we will execute a EUR 1 billion share buyback program in 2026. The consistency of this approach demonstrates our commitment to sustainable value creation and shareholder returns while investing in long-term growth opportunities.

Slide 19, please. Looking ahead to 2026, we expect to deliver a year of profitable growth close to what we achieved in 2025. For the full year 2026, we guide for high single-digit growth in sales and for profitable growth, meaning business EPS growing slightly faster than sales. Be aware that this guidance is for the full year 2026 and does not necessarily apply individually to each and every single quarter in 2026.

Sales dynamics include further portfolio optimization through divestments that will reduce sales by about EUR 200 million in 2026. We expect vaccine sales to slightly decline in 2026. Our gross margin expansion is expected to continue with minimal tariff impact following the agreement reached with the U.S. administration last December.

Underlying R&D will increase moderately. In addition to this organic growth of R&D expenses, we have added a placeholder for potential future acquisitions, particularly for Phase I and Phase II assets. Sales and marketing expenses will increase to support growth and launches, while we continue to target stable G&A expenses. Our operating income is expected to include around EUR 500 million of capital gains from disposal.

As a reminder, the profit sharing line in our P&L is increasing faster than sales growth by more than 10 percentage points. We now expect a decrease of around EUR 400 million in R&D reimbursement coming from Regeneron this year. This decrease will be more than offset by Amvuttra royalties, which are estimated at approximately EUR 1 billion based on the latest consensus. This results in a positive impact of around EUR 500 million to BOI.

Our financial outlook includes an increase of our financial expenses this year, driven by increased net debt from both 2025 and 2026 BD and M&A activities. Finally, we expect a stable effective tax rate.

I now hand over to Houman to provide an update on the progress of our innovative pipeline.

Thank you, François. 2025 has been a year of significant delivery across our pipeline. I'll walk you through the highlights.

On pipeline delivery, we achieved 12 Phase III readouts and 15 Phase II readouts and then added 10 new molecules to Phase I, including 3 gene therapies, emphasizing our greater focus on research, supported by business development to replenish our early-stage pipeline.

On the regulatory front, we obtained 20 regulatory approvals and 22 acceptances, including 9 priority reviews, in addition to other designations, underscoring the progress we've made. Most importantly, we provided patients with 3 new medicines and vaccines: Qfitlia, the first RNAi antithrombin medicine in hemophilia approved in the U.S. and China; Wayrilz, the first BTK inhibitor in ITP approved in the U.S. and EU; and our recombinant COVID-19 vaccine with full approval in the U.S. and the EU. All these highlights represent meaningful progress in delivering transformative medicines and vaccines to patients worldwide.

Please turn to the next slide. Turning to the Q4 highlights, where we received approvals, including Dupixent for CSU in the EU, Tzield for Stage 2 T1D in the EU, Wayrilz for ITP in the EU, Cerezyme for Gaucher disease Type 3 in the U.S. We strengthened our position in China with 4 approvals, something that I will return to again today. We received regulatory submission acceptance for Dupixent's AFRS in the U.S., Tzield Stage 2 T1D for children in the U.S. and SP0087 rabies vaccine in the EU.

On Phase III readouts, amlitelimab delivered more positive results in atopic dermatitis and Dupixent met its primary endpoint in AFRS. Tolebrutinib did not meet its primary endpoint in the PERSEUS study for PPMS. As a result, we will not pursue its regulatory submission. Ending with pivotal Phase III starts, we initiated the second lunsekimig study for COPD, 2 duvakitug studies, each in Crohn's disease and in ulcerative colitis and in 1 Wayrilz in IgG4-related disease.

Next slide, please. I start with amlitelimab, whose data -- recent data provides increasing confidence in progressive long-term sustained benefit and patient convenience. Data across COAST 1, COAST 2 and SHORE Phase III studies and the ATLANTIS open-label Phase II study demonstrated progressively increasing efficacy over time, with no evidence of plateau through week 24 to 52. This validates the potential for both monthly and quarterly dosing from start, offering significant patient convenience as either monotherapy or combined with topical corticosteroids, an important background therapy used in the real world. Amlitelimab was well tolerated with an acceptable safety profile.

Much of our amlitelimab OCEANA global atopic dermatitis program has now been delivered, including Phase II and Phase III studies evaluating its efficacy and safety when administered in monotherapy and in combination. Remaining studies, AQUA in patients with background TCS and TCI with inadequate response to biologics or JAK inhibitors and ESTUARY, the randomized maintenance study. We expect both readouts in the second half of 2026, completing our comprehensive package for regulatory submission.

Next slide, please. China remains a strategic priority with significant progress made by our regional team. We obtained approvals for global medicines, Cablivi, our anti-von Willebrand factor antibody for acquired TTP and Qfitlia. For China-only medicines, we received approvals for Myqorzo for obstructive hypertrophic cardiomyopathy and for Redemplo in patients with familial chylomicronemia syndrome. These approvals demonstrate our commitment to bringing innovative medicines and treatments to Chinese patients and to leverage Chinese innovation in doing so.

Next slide, please. Now let me share an update on our key mid- and late-stage pipeline projects. Our immunology pipeline has been strengthened by having delivered most of amlitelimab's Phase III programs in AD and duvakitug having advanced to Phase III for CD and UC. And lunsekimig will provide data in asthma this half and has potential for life cycle opportunities. Brivekimig is now moving to Phase IIb.

In neurology, tolebrutinib is still under review for the EU SPMS, frexalimab in Phase III for RMS and SPMS and riliprubart for Phase III for CIDP, the latter 2 with data already next year. In rare disease and oncology, Wayrilz is making progress with its life cycle planned beyond ITP, venglustat in Phase III for GD3 data coming very soon and Sarclisa expanding with a subcutaneous formulation. Our vaccines portfolio includes multiple programs across pneumococcal disease, yellow fever, meningitis, RSV and pandemic preparedness.

Next slide, please. On my last slide, I'll cover the '26 and '27 news flow updates since December's year-end late-stage pipeline review. This year, we expect the remaining Phase III data for amlitelimab in AD and Phase II for lunsekimig in asthma and rare disease with venglustat Phase III readouts, if positive regulatory submissions will follow. We anticipate multiple regulatory submissions based on data we already received last and this year as well as regulatory decisions for medicines and vaccines under review.

Next year, we will get the Phase IIb data for brivekimig in HS, followed by Phase III studies of frexalimab in RMS and riliprubart in CIDP.

My sincere thanks to all Sanofi R&D colleagues who share my commitment to advancing our pipeline from research to regulatory approval. This represents a rich diversified news flow that we believe will continue to drive value creation for patients, society and of course, for Sanofi.

So we'll now open the call to questions. [Operator Instructions] Now we'll take the first question. Please go ahead.

The first question is from Zain Ebrahim from JPMorgan. Zain?

Zain Ebrahim, JPMorgan. My first question is on the Dupixent rollouts in CSU and COPD, which sound like they've been particularly strong. But can you elaborate on how those rollouts are progressing and remind us of the biologic penetration in each of these indications and how Dupixent is faring against competition from RHAPSIDO in CSU and NUCALA in COPD? That's my first question.

And my second question is a vaccines question. Just in terms of within your overall vaccines guidance, what you're assuming for Beyfortus in '26 in terms of growth and how that looks for the U.S. versus ex U.S.?

Okay. Thanks, Zain. Brian, Dupixent?

Thank you, Zain, so much for the question. So I'll go a bit broader and then I'll focus in on a couple of those indications. So as you look at our performance in 2025, really strong performance, 25% growth year-over-year, and we culminated that with a really strong Q4, and I'll talk about that here in a minute, 32%. Now this was driven not just based on those 2 indications that you highlighted, but the foundation of our indications grew as well because it's a volume-driven growth story that we saw in 2025.

Now of course, those were on our base indications, but the launch of COPD, the launch of CSU and the launch of BP were new sources of growth that were not in our base in 2024, which allowed us to accelerate growth, culminating in that Q4 that I talked about there just a bit. And again, I'll highlight COPD and CSU in just a minute. But that 32% growth that we saw at the end of the year is really a reflection of those not being in our base, but being strongly in Q4 performance that we saw.

Now as we go forward into 2026, we expect that growth to normalize as we talked about, as we've seen before, and we're well on track to deliver our longer-term guidance by 2030 of greater than 22 -- around $22 billion sales.

Now specifically on COPD and CSU, I've spoken about COPD quite a lot. It was an inflection point for this year, as you can see from the performance, which was, again, being the first biologic, really the first innovative therapy in more than 10 years in the COPD space, and we've seen a really good response from the physicians. Now remember, we were already in the pulmonologist offices with asthma and having the leading asthma therapy beforehand. So it was a really nice complement.

CSU is a very similar story. We've seen a really rapid uptake in the CSU launch. But again, remember, we were also already the leader in the dermatologist offices and the allergist offices with multiple indications, now 8 indications in the U.S. So we've seen that those have contributed really nicely to our growth.

Final point I'll make on CSU because you asked a question about the competitors, RHAPSIDO. We don't really zoom in on one. We think competitors across all the immunology indications are really good because the bio penetration rates are extremely low. AD is only 18% still to date, and it's more than 8 years into our launch. CSU, we believe, is in the low teens. So again, this is a place where you're going to continue to see the market growth as well, which is great when we have new competitors come in.

Okay. Thomas?

Thank you, Zain, for the question. So as it comes to Beyfortus specifically, first of all, let me say that we are happy about the 2025 performance with an increase of a bit more than 9% year-on-year. When you recall very well that on the Q2 earnings call, we had mentioned modest growth expectation for 2025. So happy about the performance. As you've noticed, it's a performance that's coming from broadening the reach to more and more countries, and Beyfortus is now available in more than 45 countries.

So as it comes to 2026 outlook, it's a bit early to be very specific on the performance of the product. However, I can say a few words about the dynamics. I think what's very important to have in mind is that there is a little bit of a different dynamic between U.S. and non-U.S. I think that's included in your questions.

On the U.S. front, you have seen the recent changes on the pediatric immunization schedule, still very recent. As you have seen from a recommendation perspective, nothing has changed for Beyfortus in terms of recommendation or coverage. Now will it create and to what extent confusion for parents and HCPs? Too early to say. We need to see that in the coming years and we'll be -- in the coming months, sorry, and we'll be able to tell you a bit more at Q2 earnings call more about Beyfortus in the U.S.

As of outside of the U.S., we will expand the geographic coverage as we've done over the past 2 years. And the last point I will refer to on Beyfortus. For those that have not seen, there has been a very nice JAMA publication at the end of December 2025. This is the first real-world evidence head-to-head comparison between the use of either maternal immunization or passive immunization with Beyfortus. And you've seen that on very single endpoint, Beyfortus is doing better than the competitor. Thank you very much.

Thank you for that, Thomas.

Next question is from Ben Jackson from Jefferies. Ben?

Brilliant. Just 2 for me, please. I guess, previously, you've spoken about a range or numbers of peak sales estimates around amlitelimab. And perhaps now that we've had some additional data, has your view on any of this changed at all?

And Houman, perhaps if you could flesh that out. And you've had a little bit of time to talk to KOLs now and figure out how they're feeling. What is the feedback that you're getting on the additional results, not just kind of the positive parts on it, too, but if I can push you, what are the pinch points? What are the bits that they still got a little bit of uncertainty or questions over as well? And how can you address those? So just rounding that up would be brilliant.

Thanks, Ben. Brian, do you want to give us a sort of broad view?

Yes. And thank you so much for the question, Ben. I think if you think about the broad view of this, and again, remember that we were always bullish on this from an AD perspective. And I think Houman will probably talk about that.

As you think about this marketplace, it's still really developing. We talked about the bio penetration, I mentioned 18%. It will more than double. I'm confident that it will more than double. If you look at what psoriasis has done, this is a marketplace that's going to continue to grow. And if you look at it today, as new mechanisms come into the marketplace like we've seen, it actually accelerates the growth of the marketplace, much like psoriasis and so on and so forth. So having a new mechanism like this with a variety of areas in which to differentiate it, I believe -- I mean, we remain extremely confident about the opportunity in that big marketplace.

And Houman, do you want to...

Yes. Just to top and tell what Brian has said, I couldn't support more the importance of a novel mechanism in this space, which goes beyond a straightforward anti-cytokine blockade. Of course, that's an excellent mechanism in disease, but the addition of a T cell modulator with the promise, and I underline the word the promise of long-term immune normalization is obviously very attractive in the conversation.

You are right to call out the importance of being more data-driven. And of course, we've consistently shown the difference between this molecule that has a Q4 and Q12 dosing optionality, which means down to after loading dose 4 injections a year, which not only provides optionality for patients but also site of injection, et cetera, which will matter.

I'd also like to -- both of those are really important, but I'd like to not only underline the importance of the mechanism and the optionality, but that this molecule remains aligned with our initial benefit risk assessment, which is ever so important in this space, which is hugely biologically underpenetrated. And Brian, at the very beginning of the call outlined the importance of having options for these patients in terms of therapeutics.

So finally, you asked discussions with prescribers. We did many hundreds of interviews over the last couple of years, including at the recent meeting in Paris. And I can genuinely say that there's enthusiasm about a novel mechanism of action in this space. Thank you very much for the question.

Thank you.

Next question is from Seamus Fernandez from Guggenheim. Seamus?

Let's try it again. There we go. So just a couple of questions. First one is on the kind of Kaposi sarcoma case that we saw. Can you provide a little bit more detail on that as it relates to amlitelimab? And is this on mechanism in your view? Or is it more a reflection of the sort of specific patient profile in that particular case? And just wanted to confirm that there were no and have been no additional cases seen in the overall program for amlitelimab.

The second question is on lunsekimig. I think you made a comment at a conference earlier this year, specifically that there's a contribution of -- that you believe there's a contribution of TSLP in some early atopic dermatitis data as it relates to lunsekimig. I was just hoping you could clarify and confirm that comment and your views and hope that lunsekimig in that formulation -- in that disease state could potentially have a role.

Okay. Houman?

Yes. Thank you. Multiple parts to that question. Number one, let me do the second one first. Just to very quickly take that off the table. Yes, there is existing data, not with our molecule, but other people's molecules that TSLP may indeed have a therapeutic benefit in the treatment of atopic dermatitis. Obviously, IL-13 is well established in this space, the combination of TSLP and IL-13 indeed may have an additive or indeed synergistic effect. We are testing that clinical hypothesis will be very data-driven. So we look forward to seeing the results of lunsekimig, not only in asthma and its related adjacencies, but also in atopic dermatitis.

And then as you outlined in the amli question you composed to sarcoma, the answer to your question is that all immunomodulators come with a theoretical risk of infectious complications or increased infectious risk. Kaposi's sarcoma unequivocally is caused by herpes virus, HHVA, sort of a standard herpes virus. And it's not surprising that a herpes virus will be associated with an immunomodulator as they are with all other immunomodulators. There is some genetic evidence to suggest perhaps that with amlitelimab, there may be a differential sensitivity to some or other herpes viruses.

So as you say, potentially on mechanism and the very first ID that we put out before we ever started the Phase III as this was anticipated and was not regarded as a significant issue of concern. The benefit risk profile with this molecule is in line with everything we've said. And as is our activity, we will continue to produce not just with Kaposi's sarcoma, but all the broader safety and benefit of this molecule as we continue to publish the data sequentially until the end of OCEANA studies.

Next question is from David Risinger from Leerink.

Yes. So congrats on the fourth quarter performance. I just have a couple of questions. First, Houman, in terms of the amlitelimab press release that you issued recently, when do you expect to disclose full results from those studies?

And François, business EPS is expected to grow faster -- or slightly faster than sales this year despite losing R&D reimbursement from Regeneron during the third quarter. Could you just talk about the offsets to that? And looking forward to 2027, how you're thinking about prospects for growth and earnings as well?

Thanks, David. Houman?

Yes, a quick answer to your question. I think we committed to presenting the COAST 1 data AD, which I think at the end of March in Denver this year, subject to the -- on conference organizers, [ clement ] nature, we may be able to put COAST [ 2 ] and SHORE in there, that's still subject to discussion. So we hope to be able to present most of the data to you by the end of March.

Okay. Thank you, François?

Yes. David, as far as 2026 is concerned, to start with, indeed, you mentioned it, we will have a decrease of the R&D reimbursement by Regeneron of EUR 400 million this year. It was initially thought it would be EUR 300 million, but since Dupixent is growing faster -- even faster than we thought, we will accelerate this determination of the reimbursement earlier.

So we have a negative impact of EUR 400 million this year, but it will be more than offset by the Amvuttra royalties, which are going to increase even further than we thought. So we had almost 0.5 billion of Amvuttra royalties in '25. It will be probably around EUR 1 billion in '26. So we'll have a net between the 2 items in terms of impact on the BOI of about positive EUR 100 million this year in '26.

In '27, we had initially thought that we would have the full impact of the termination of the R&D reimbursement by Regeneron. We expected initially that it would be a decrease of BOI of about 800 million in '27. It will be a bit less, probably with what we see today, around EUR 700 million, as a consequence of what I said earlier. On Amvuttra, it should be probably around -- it's still early to say, but further increase of EUR 300 million. So the net between the 2 will be probably a negative in '27 at BOI level of minus EUR 400 million, which is a bit better than what we had said last time.

Next question from Simon Baker from Redburn.

Two if I may, please. Firstly, one for Houman. You've had a bit of a rationalization of your Phase II portfolio. I just wonder if you could talk us through any overarching principles that guided those decisions and future development plans?

And then secondly, moving on to Dupixent. The main patent goes in March 31. But as far as we can tell, you've got about 40 patents which expire between late '31 and February 2045. So I just wonder if you could give us your thoughts on life after March 31 in terms of the potential LOE for Dupixent?

Okay. Houman we'll get you and then, of course, quickly to Roy for a moment.

Thanks for the question. The -- when I started 2.5 years ago, it was very clear that we have a dynamic allocation strategy. We are good stewards of capital, and we need to ensure that every dollar is well spent. So the overarching strategy, which François and I hold hands on, is that we will, on a regular basis, now on at least quarterly basis, guided by AI establishment of value, we will dynamically allocate -- reallocate resources. And what that means is there'll be some programs that stop. But of course, it also means that we will double down on some programs and we'll do the right things even if they're hard. So the overarching principle is very simply in relation of capital allocation to value.

Thank you. Roy?

So Simon, thanks for the question. We do expect Dupixent to be protected by its patents beyond March 31 in the U.S. That's the reality. As you can imagine, lots of innovation, lots of indications and counting. These are being recognized by multiple -- and thank you for going through them, granted and to be granted patents ranging from [ '31 to '45. ] We believe we have a very strong patent portfolio, which we intend to vigorously defend. You'll understand, it's too early to speculate on specific dates of biosimilar entry, if and when patent fights commence, we'll be able to give you more details of what is being challenged and where, but we feel we're in a good place with multiple patents.

Okay. Thanks, Roy?

The next question from Luisa Hector from Berenberg. Luisa?

I wanted to ask on vaccines, please, because if we look at 2025, you deployed about EUR 3 billion on business development, M&A. So I wondered if you're putting that together with your R&D, is that a significant step-up in capital allocation to vaccines? And how should we think about the opportunity cost versus building your drug pipeline?

And then perhaps a little more color on Dynavax. It looks like a neat deal. So how did you value it? Is this a U.S. opportunity mainly? Is it catch-up and then you move to an annual cohort eventually? And should we think about shingles as a booster opportunity in the over 70s?

Thank you, Luisa. Thomas, 2 good questions for you.

So I will start in the reverse order, Luisa, if you don't mind. So on Dynavax, let me first start by saying that the transaction is not closed yet. So as you know very well, we are still processing. But going back to your question, I can talk a little bit about the rationale.

A few elements I'd like to highlight on this. First of all, it goes very well with what we have discussed before with the fact that we are very present on a significant part on the pediatric immunization schedule. But as we discussed in the past, we see, in terms of demographics, simply an increase on the older adult group and a decrease over the past few years on the pediatric and that's why our strategy is more and more focused towards the older adult group in terms of pipeline development.

And the Dynavax proposed acquisition very well fits that profile, with [ HEPLISAV-B ] in mostly focused on the U.S. So that's really the cornerstone for this product with a very differentiated product, with a 2 doses regimen versus 3 doses for any other competitor. And you've seen the progress in terms of market share. And we believe, by adding our commercial muscle there, we can further improve the performance in this segment.

In parallel, you have mentioned Shingles, very interesting Phase I/II data there on the Dynavax shingles candidate. We believe there's a great possibility in terms of marketplace if there is a candidate that comes with a significant similar efficacy than the current incumbent in that place. However, with a much better tolerability, and we believe that the Dynavax technology will enable that profile.

Going back to the first part of your question on capital allocation. So if you look at it from the way you framed it, indeed, there has been an increase in 2025, but I'd like to maybe take a step back and explain to you how we look at it. We don't look at capital allocation or acquisition per TA. The way we look at it is what is the strategic fit of every single possibility in terms of acquisition or licensing it? Does it fit our portfolio? Does it fit our capabilities? Does it fit our long-term perspective on the business?

We have a very strong long-term perspective on the vaccination business, where the fundamentals are very strong. We believe that the acquisition we have made, both early and later stage in 2025, do reflect and do fit well that perspective. So we are not looking at it partly. We are really looking at it -- what's the strategic fit, what is -- are we the best owners? Can we deliver significant added value? And if that's the case, at the right price, then we go for it.

Yes. Next question from Pete Verdult from BNP. Pete?

Yes, Pete Verdult, BNP. Apologies if some of these questions have been asked, but we've had a rather long competitor call to finish off. So just 2 questions. Thomas, sorry to come -- to stay on vaccines. Can we spend some time on the outlook in light of some of the recent developments that you've already touched upon, particularly in the U.S., on the context in terms of the 10 billion target you set for 2030. So just looking for a little bit of a ballpark reminder. What percentage of your business today is exposed to these U.S. pediatric vaccination schedule changes? I know we're not expecting any imminent impact. But just to remind us what the ballpark exposure is. Could you flesh out a bit more some of the U.S. and ex U.S. Beyfortus dynamics?

And then when it comes to flu, what's your sort of -- on a net basis, how are you thinking about the outlook? On one hand, you've got mRNA threats receding, but you've got investor concerns around risks from competitor preventative assets rising. So net-net, how are you thinking about flu? So that's the first question.

And then much more succinctly, just Paul or François, just on capital allocation. Given the pipeline disappointments, is it fair to assume business development activity is set to accelerate significantly going forward? Any -- are you really not going to talk about specific assets, but just your intention to do BD. Is that set to step change?

Okay. Thank you. Thomas and François?

Yes. So welcome first, Pete. And indeed, there was a bit of a similar question at the front stage, so I'll be pretty fast. So on the outlook about vaccines, and I think to be clear and explicit, you're referring to the recent U.S. [ childhood ] immunization recommendation changes in the U.S.

Maybe a few words about this and then we'll turn the page. So those recommendations, to be clear, have been pivotal in making sure that we can prevent life-threatening disease in U.S. citizens for many, many decades. The recent and sudden shift there has been in early January to a 3-tier childhood vaccination framework, full generate confusion for both parents and providers. We don't know that. We don't know yet if there will be a concrete impact in terms of this year, but it's way too early to look at that.

A couple of points, though, in terms of dynamics I'd like to highlight. First of all, you've seen that every single medical society and by far, the very, very fast -- vast majority of HCPs have decided to stick to the previous immunization schedule, first point. Second point, you have not missed the fact that all vaccines remain covered by insurance or by Medicaid or Medicare, depending on the different products. So it's not a question of coverage. But Pete, you're right, there could be some confusion in terms of U.S. vaccination schedule.

The way we look at it is what can we do and we are focused on our energy and our actions. We are engage proactively with HCPs with clinical societies in every single country, U.S. and non-U.S., we expand the benefits of our product, how they are differentiated from others, and we are focused on what we can do. So that's really for the situation in the U.S.

You mentioned a couple of things on Beyfortus U.S., ex U.S., we mentioned that in the call before. But as I was mentioning, happy about the '25 performance, 9.5% increase. '26, too early to say. We expect to give more guidance on this as we move forward in the year, probably in the Q3 earnings call, we'll then a look at U.S. versus ex U.S.

Your second point was on flu and how we look at the marketplace moving forward. You've seen that Q4, flu performance was significant. Maybe it's the opportunity for me to mention a couple of things. It's the second season in a row, 2 years in a row, 2 winters where there has been a massive increase in terms of influenza hospitalization across the northern hemisphere on this side of the Atlantic or on the other side, which is a very important reminder of the fact that these cases can be prevented pretty simply with the vaccination, including with differentiated flu vaccination.

Happy about our 2025 performance, which ends up showing that our market share will increase, especially thanks to our differentiated products, Fluzone High-Dose, which has shown great data again this year clinically as well as Flublok [indiscernible], very important differentiator moving forward. Obviously, this comes in a very specific situation, i.e., a decrease in terms of VCR in the U.S. and a slight increase of influenza VCR in Europe, but you understand from a value perspective, these are very different markets.

Moving forward, we'll probably give some more guidance on flu at the Q2 earnings call. MRNA on flu is not a concern for us for 2026. It will not be present. It may -- it's not a concern for us in 2027 neither, simply because as we discussed before, people are looking for the right profile in terms of efficacy and tolerability profile. So we think we are well positioned. We have the right products. More to come after the prebooking season, so probably around the Q2 earnings call.

Thank you, Thomas. François?

Yes, Pete, on the capital allocation question, well, first and foremost, I presented it earlier, we have a strong balance sheet that gives us flexibility. That being said, we will remain very disciplined. So we will use our capital essentially around 3 criteria in terms of external growth, BD and M&A. Strategic, essentially around our 4 existing main therapeutic area plus potentially some white spaces. We want to make sure that we bring scientific differentiation with best-in-class, first-in-class assets and differentiated assets, and we want to secure financial return as well.

We are certainly not chasing growth for the short term and medium term. You saw our growth profile last year. You see our growth profile for 2026, which is at the upper end of the industry. So not chasing growth. But we are rather focusing on the longer term to complement our pipeline. So we have a certain number of assets in our pipeline. We know as well that we have -- we discussed it a few minutes ago, to manage the [ LOE ] of Dupixent at the earliest in 2031, we just discussed it.

So as a consequence of that, we will try to focus essentially on Phase I, Phase II assets, which is our priority. We could as well, as we did last year, by the way, complement it with commercialized assets, which will probably, to a certain extent, mitigate the BOI/EPS impact. Anyway, we will remain very disciplined. And I would not say we have time because time flies, and we have a feeling of urgency. But once again, we will be super focused and super disciplined.

The next question is Steve Scala from TD Cowen.

Steve?

Two questions, please. First, I'm curious why Sanofi has not been as forthcoming as Regeneron on Dupixent life cycle extension programs. I'm referring specifically to what Regeneron shared earlier this month. My understanding is that you have similar rights as you do now. So are you simply not as confident in those programs? So that's the first question.

Second question is, in the past -- in past quarters, Sanofi has noted on the Dupixent slide that Dupixent was #1 in new-to-brand Rx and #1 in total brand share in the U.S. Curious why that was left off this quarter. Is that due to competition, specifically from [ Ebglyss ]?

Okay. Brian, 2 questions for you.

I'll start with the second one. Steve, thanks. That's a really nice setup. Sorry, we missed that on the slide. We are #1. We remain #1 in every single indication across each of our specialists. So apologies, I think we are now adding more things about new indications and whatnot. We probably left that off there, but no. And I don't foresee that changing anytime soon.

Now as it relates to LCM and forthcoming this from a Regeneron standpoint. I'll build on what Roy said. First, it starts with our IP. First, I have to think about that, how are we going to continue to defend that long into the future. And so Roy gave a statement there. So we've got quite some time. But we've been building along with the alliance and LCM strategy, as you would imagine, and we will reveal it in due course. Most likely the first half of this year, you'll get an update on where we stand as far as what we're doing with Dupixent specifically. Might be formulation related, so on and so forth, but you'll get a bit of an update there as well.

Additionally, we are working on the next-generation IL-4Ra with Regeneron. Regeneron talked about this a little bit at JPMorgan, but we continue to work on -- and collaborate on programs that we have across the alliance. And again, that could be really meaningful as a follow-on Dupixent and so on and so forth. But beyond that, given our success across the alliance for quite some time now, we're always open to and interested in considering future collaborations with Regeneron, as we said at JPMorgan. So I feel like we're in a really good spot right now, more to come in the very near future.

Yes. Next question from Sachin Jain from BofA.

Just 2 questions from me. Firstly, big picture, I guess, for Paul. There's a sentence in the press release that talked about midterm profitable growth for 5 years. And at a recent conference, you talked about potentially delivering, I guess, implied with teens EPS. So just a big picture from your side. What was the intent on that signaling and giving you consensus as large as their ex pipeline? So just thoughts as to inserting that commentary within the debate for investors.

And then secondly, one for Houman. Do we get any further TL1A Phase II data through the course of '26 that further profiles the asset as we start looking to that Phase III data, I guess, into '28?

I should maybe let François comment first on profitable growth.

Yes, profitable growth. I think that we included that comment in the press release because we had a lot of questions. We just wanted to make sure that the market understands that we do expect to deliver an attractive level of growth to start with for the next 6 potentially years and that this will be coming with profitable growth as well because there was a question a couple of quarters ago about our capacity to deliver profitable growth each and every single year. I confirmed it a little bit earlier today. There was a question more specifically about '27 given the end of the R&D reimbursement with Regeneron, but it's not a defensive move, it's just a confirmation of the way that we see the outlook for the medium term.

And your second question, the answer is simply, yes. We will have maintenance data for the TL1A, at some point this half.

Next question from James Gordon from Barclays. James?

James Gordon from Barclays. One question was on business development. I know you've had some questions on this already, but a follow-up to those, please. I've seen some attributive comments this morning about the company having a EUR 14 billion to EUR 15 billion BD firepower amount for this year. And assuming that is right, that was the comment, what is the thinking there? Is it that you do -- you can really fire that immunology to get more assets that could complement a follow-on from Dupi? Or with immunology looking a bit crowded and you've got a lot going on in immunology anyway already and a bit more competition coming as well. Could you focus beyond Dupi and say, right, we're going to broaden out other areas of the business. So could it be like EUR 15 billion on one big deal? And if so, is it more likely to be trying to do even more immunology or could you diversify?

So the second one I was just going to say as well. So [indiscernible] for AAT, I didn't see an update on the regulatory plans. Have you now spoken to the FDA? Or if not, when will you? And do you think you can file on the data you've got?

Why don't we get François, then...

No, I will just -- I will answer on the EUR 15 billion, which is I would say the upper limit of what we can do to maintain our [ AA ] rating. So it has nothing to do with where we can invest by TA and so forth. As I said, I mean we are interested fundamentally in strengthening. Our position in our 4 existing TAs plus potentially white spaces. We could always contemplate going further than that. But the EUR 15 billion was the, let's say, technical limitation to preserve our AA rating.

Thank you. Houman?

Yes. I'll follow Brian's lead. Thank you for the setup. We had excellent data, as we announced late last year. We'll imminently, certainly, this half of the year, go to the FDA to have broader conversations on the trajectory of that molecule as we previously suggested.

Okay. I think was the final question, was it? Or there's next question?

Yes. Next question from James Quigley from Goldman Sachs.

I've got 2, please. Hopefully, they haven't already been asked, but I'll give it a go anyway. So firstly, on -- following on from Steve's question on the Regeneron portfolio. The IL-13 assets were not in the alliance. So was that a Sanofi decision? So is it that you think lunsekimig is more attractive option for IL-13. Can you give us any color yet as to why you're excited about the IL-13 and TSLP combination for lunsekimig?

And then secondly, on the hemophilia portfolio. ALTUVIIIO continues to show strong growth. What are your expectations here in terms of gaining additional share into 2026? Are you willing to give a peak sales forecast here now that you hit blockbuster status? And also for Qfitlia, the launch is progressing steadily. You've got China approval now. So what's the feedback been in terms of where Qfitlia is being used? Are there any lingering thrombosis concerns with the product that may be holding it back?

Okay. Thank you so much. Okay, Brian, over to you.

Yes, James, thanks so much for the question. I briefly addressed it just before. So there's not a decision necessarily on the IL-13. I think we talked about this a little bit at JPMorgan not so long ago. But as I said before, we are -- it's not in the alliance currently, but we're always open to having conversations with Regeneron about potentially including it in the alliance. As I also said, we have a long-acting IL-4 RA that actually is in the alliance that we're actually working on right now as a follow-on asset to [ dupilumab ]. So again, long withstanding great partnership with Regeneron, so we'll always have conversations with them about what we might do next together.

And as it relates to Qfitlia, you want me to tackle the Qfitlia one next. Qfitlia is again, it's still early days as far as the launch goes. We said from the very beginning, this is really a very cool therapy in the sense that it is a very targeted kind of precision medicine, if you will, come to the diagnostic as it relates to antithrombin levels. And again, what we said is we'll have a little slower ramp. I think it will be a lot stickier on the back end from a patient standpoint as physicians get really -- they can dial it up and dial it down as the patient presents and it's really more personalized by each patient. So far, we've heard really good feedback from the marketplace. No concerns as far as safety goes so far. But again, it's early days and promising. We'll keep you up to date in future calls.

Okay. Thanks, Brian. And then I think there may be one more?

Yes, one more question and last question from Graham Parry from Citi. Gram?

Apologies if it has been asked, I think it has. I just wanted to check on itepekimab. You're saying about looking at additional data for the path forward. So can you give us time lines on what it is you're looking on the data and the clarity and time lines on path forward for that molecule? And then tolebrutinib in the U.S., are we just correct to assume no path forward in the U.S.? If you could just comment on rest of world regulators' attitudes to the ability to monitor compared to the U.S., that would be very useful.

Graham at Citi, and those that will know, no, I have made that point. Thank you for the question. The first question, let me do it in reverse, tolebrutinib's approach is pretty straightforward. We're waiting for regulatory comments from rest of world, as you say from EU. And we'll see where we take it from there.

And then on itepekimab, as I consistently said, the next steps for itepekimab will be determined by interactions with the FDA predominantly to establish exactly the requirements for a replication study for Phase III going forward. As soon as we know, we will commit to sharing it more broadly in partnership with our successful alliance partners Regeneron.

Okay. Thank you, Houman. Thank you, Graham. Well, thanks for this last question.

In 2025, we achieved a strong year of profitable growth. Sales increased by 9.9% at constant exchange rates, while business EPS improved significantly faster by 15%. We launched 3 new medicines and vaccines: Qfitlia, Wayrilz, and Nuvaxovid. All this was made possible by the dedicated effort of all Sanofi colleagues worldwide.

In 2026, we expect sales to grow by a high single-digit percentage and business EPS to grow slightly faster than sales. We anticipate profitable growth to continue over at least 5 years. Based on our pipeline, combined with external growth opportunities, our ambition is to pursue earnings growth into the next decade.

With this, I would like to thank you for the interest in Sanofi, and we'll now close the call. Thank you.

Welcome to the JPMorgan Healthcare Conference. I'm Richard Vosser, European pharma analyst for JPmorgan. It's my great pleasure to introduce Sanofi. From the conference we have 3 of the very senior management here to entertain us now. Paul Hudson, CEO; François-Xavier Roger, CFO; and Houman Ashrafian.

You fully butchered every name.

Every name, every year.

Every year.

It's consistent, but that's what we like. So I better shut up then and hand to Paul for a few introductory remarks, and then we're going to chat together.

Thank you, Mr. Vosser. We appreciate that.

That was wrong, Paul.

Great -- we only have a handful of slides, but I'll just -- we'll put a -- I have 1, Houman has a couple. Thank you for making the time. It's been an extremely busy year last year for us, and we had a couple of challenges in R&D, which I think are well communicated. We also made a very important commercial progress. We were growing 8.7% through Q3. Script trends, if they stay consistent through the remainder of the year across the major drivers of that, we're going to be close to double-digit growth. That double-digit growth profile we think we can maintain for the next half decade plus. And that puts us in quite a rare group in terms of how well we're executing. We have a new blockbuster with ALTUVIIIO. We've got close to EUR 4 billion in launch revenue. So we're working fast to offset the potential Dupixent LOE in the future. And we have the ambition to grow EPS through the Dupi LOE.

So we're well underway on our plan of transformation or capital allocation. We've exited consumer. We hopefully have added Dynavax. We've done some things to try and continually modernize and equip as best for the future. We executed on Blueprint, delighted with that. And so the journey really strongly continues for us. We're well aware that we have a lot to prove still in R&D. We have some huge readouts ahead of us early this year. And with that, maybe I'll hand a little bit to Houman.

Thank you, Paul. Happy New Year. Last time I'll say that. Delighted to be here at JPMorgan. As you can see from this slide, in immunology, we have an exciting year ahead of us. Amlitelimab will read out COAST 2 in the near future. It's important to also call out there's a number of other studies coming, including SHORE, which is the combination study with topical corticosteroids germane to how atopic dermatitis is practiced today. We look forward to those, but it's not all about our Rockstar amlitelimab. We have duvakitug data coming later in the year, our TL1A partnership with Teva. And we have excellent and interesting opportunities to assess the value of combination therapies in bispecifics, in asthma and beyond in lunsekimig. It's not all about immunology and autoimmune disease. We are excited to be a rare disease company and our commitment to the patients remains. We have a number of rare disease and oncology readouts, and we continue to be active both in vaccines and in neurology.

As you can see on the next slide, the data flow is substantial in the first half of the year and will be extended further throughout the year, both in terms of early and late trial readouts as well as regulatory approvals. It's a good year to look forward to. And we will supplement being here in JPMorgan [indiscernible] will supplement commendable internal pipeline with partners that already exist in partners of the future.

Excellent. Thanks, Houman. Thanks, Paul. Maybe we could start. Maybe I'll just complement the jacket this year. It's very, very nice. Socks last year, jacket this year. So but Paul, you were in the White House at the end of last year. Maybe you could just talk about your thinking on U.S. pricing going forward for the industry. You're going to be Head of Pharma this year as well. But the impact for Sanofi, what are we thinking?

Well, we've said over the short term, we'll have to work very hard to make the impact manageable, and that's our intent. It was -- I would like for everybody a tough negotiation with the government. I think they got, I think, what they needed, but we felt well represented on some of the team that pulled that together are in the room today and congratulations to them. I think most of the companies found themselves roughly in the same place. It was -- I think as François calls it cost avoidance. The tariff piece was an unnecessary drag on the thinking for '26. We've been able to remove that. We've made some concessions to do that. But I think we feel very comfortable in our outlook. We haven't shared '26 guidance yet, but when we do, you'll hopefully understand how we put those 2 things together.

The White House experience is really grafted in an environment to go into more detail on that. But the President did say something extremely important at the end of his speech. If you are watching very carefully, he said, now we turn our attention to the insurers. And I think as incoming Chair of Pharma, that's a very important statement that he's made. If he attacks it with the same level of energy as he did MFN, that may be an opportunity, and it also may be a challenge. I offered to bring pharma back to the table to make sure that he felt that would be good partners in making sure that we create even more visibility with the insurers for the benefit of patients in the United States.

Lastly, the comment really about the complexity around GDP adjusted pricing in basket countries outside of the U.S. and what that means for future launches. I met many heads of state in Europe over the last few months. Obviously, they're concerned at the level of U.S. attention to pricing and what it might mean for new launches. They're right to be concerned. But frankly, as I said, the 3 heads of state in Europe in the last quarter of the year, 54% of the medicines that are approved by the EMA are not available in Europe today, long before the President turned his attention to it. So they have some work to do to reward innovation, and we'll be looking at that, too.

And just one other comment in this area. The vaccine policy. We've seen some policy changes, CDC recommendations, et cetera. Just how should we think about that from your business point of view? I suppose we're particularly thinking about Beyfortus and some of the RSV changes.

Well, look, there's 50,000 plus newborns that were going into the ICU in the United States every year in a very distressing circumstances, many with complications that lived long after the RSV had passed. We've been able to drop that close to 80% or 90% with the launch of Beyfortus. We're very proud of the work. It's clear this administration has particular sensitivity around vaccination and indeed pediatric vaccination preferring to give the parents the choice. We know that is a very delicate line to walk because not everybody is well informed. And of course, when you're trying to protect communities that leaves too much open to variability. We can't do much and I am asked all the time, what are you going to do to fix this? And the truth is we just need to stay extremely objective and keep presenting the evidence.

There's really very little else we can do. Then we'll see where Kennedy gets to. We'll see how it gets through to the midterms. And for most of our work, we plan longer than 3 years. So we will have to maintain a steely focus on the long-term future vaccines and deal with any uncertainty around vaccine coverage rates in the short term based on misinformation, Facebook posts and statements from the top. We're just going to have to deal with it, try and provide patients and parents the very best advice we can.

In your opening slide, you highlighted the strong growth of the first 9 months and highlighted strong growth potential out towards the 2030. How should we think about that growth developing going forward '26 and beyond relative to the near double-digit or around double digit of '25?

Well, I'll let Francois comment on the profitable nature of the growth. But I raise it upfront because to have high single-digit, close to double-digit growth with a clear line of sight through 2030 and perhaps beyond with that puts us in a rather unique club. We're well aware of the journey this company has been on. We've simplified. Again, we've become more of an R&D-led pharma company and got away from consumer. And we've done everything to really make the company one of the sort of leading R&D-led organizations. We're still missing the proof points, I am the first to admit it. And we've taken a lot of shots that are first-in-class, best-in-class. With the readouts that are just ahead of us, we hope to reclaim some of the sentiment in our direction because we're trying to navigate what we call the 2 very simple basics, top line pipeline, top line pipeline. Top line, we're one of the most predictable in the big pharmas because of the lack of LOEs. Pipeline will still prove yourself. But to talk about the profitable growth, Francois, maybe you want to comment.

And maybe to complement what Paul said. What is important to understand as well is our growth profile, so we'll be around high single digit to double digit till the end of the decade at least. But we are not Dupixent-dependent. So Dupixent is going to contribute about 1/3 of the growth. 1/3 of the growth will come from already marketed products, on which there is a new commercial risk and not an R&D risk and 1/3 will come from products to be launched. So I think that it's a well-diversified profile. So obviously, we are talking of profitable growth as well, which means that our BOI and our EPS will grow faster than our sales, which means that we will see discipline in our spend. And just to give you maybe a little bit more color, we do expect to continue seeing our gross margin increasing? Anyway, the product mix is probably providing a tailwind of about 1 percentage point a year.

Just for information, we were 5 years ago, about 4 to 5 percentage points behind our peers. Today, we are almost at par with our peers. We'll continue investing significantly in sales and marketing given that we have a superior level of growth. We'll be disciplined and we'll make choices on R&D. But we will continue increasing our R&D spend. And we will be super disciplined on G&A, which means basically we expect to see G&A being around flat. That will give us the profitable growth.

And just to add to that, we -- I think people don't fully see how radical the transformation has been in the company. We're 30,000 people lighter than we were 5 years ago. And extraordinary really in terms of the evolution of the company, we've lost 1/3 of our manufacturing sites. We've divested them because we're trying to position ourselves on this margin expansion and on this BOI run at profitable growth. We're asked a lot even this morning, do you have enough R&D capacity. Can you -- if you turn the cards over positively, can you get it done? And we believe, because of some pruning and some prioritization, we have enough bandwidth to carriers forward to be able to launch enough to generate that 1/3 from products yet to be launched. So I think we feel very good about it. Again, we still have to show some positives out of R&D to, I think, provide the confidence that the multiple can move.

And we'll come to the pipeline in a second, but just business development in terms of supplementing the pipeline. And you talked about managing the R&D spend being disciplined. As you look to supplement the pipeline, I suppose there's 2 questions. One is on that R&D, how you make room, but also what's the plan in terms of business development, more assets later, earlier? Where should we...

Well, I think there's two. I'll let Francois comment. There's 2 categories for us. I think we're light in Phase I. We may be 8 to a dozen high-quality programs that we want to add internally advanced into Phase I or to some of the conversations we have here will help that. We think we're a little bit light in early. We think we have enough in mid- to late stage, but I think we have to accept to underwrite the mid late-stage pipeline, and we should continue to add externally. And that's not an easy thing to do. It's a very competitive space with many companies with huge LOEs ahead of us are rushing to add those sort of mechanisms. We're looking to things that launch in the sort of '28, '29, '30 horizon because it's just -- it fits our profile better. Some are trying to go fishing much earlier than that.

And we're open minded. We have a great balance sheet. We have cash flow increasing. We have a great credit rating. We feel like we can really do some things. Last year, we took people a little bit by surprise with Blueprint. Now the premium on Blueprint looks like it was a genius piece of work. But we've got a blockbuster there and already on flight to being a blockbuster. So we're excited about that. You should see us do more things not too toppy, but with the intent of derisking mid- late stage and adding more aggressively in Phase 1. Francois?

Yes. So in BD and M&A, we will remain very disciplined as well. And we did that in 2025. If you look at it at the beginning of '25, we said we would like to retain our AA rating, which gives us in the context of the disposal of a majority -- of a controlling stake of Opella, but capacity for about EUR 20 billion, almost $25 billion last year. We did half of it because we didn't find the right targets. We are looking at essentially investing in our 4 therapeutic areas plus potentially some white spaces, but we don't feel any pressure to do so, okay? We would like anywhere to complement what we have in our pipeline in order to drive the LOE of Dupixent, which will be coming at the beginning of the next decade, but we will remain very disciplined anyway. And that's what we have done last year.

We have a good track record, by the way, on BD and M&A. Just for your information, we spent -- we invested about EUR 45 billion, more than $50 billion over the last 10 years, and we lost only -- sorry, for the only, but 10% of it, about EUR 4 billion to EUR 5 billion, which is not a lot in our space, I would say. Even if we had not lost anything, I would have been worried that we would not have taken the right level of risk. So I think that we have created a lot of value through BD and M&A. It doesn't mean, by the way, that if we did it in the past, we will do it in the future, but I think it's a good starting point.

Makes sense. Maybe turning to the pipeline, and you mentioned amlitelimab and the upcoming COAST 2 data. But maybe if we could just touch on what we've seen so far from COAST 1. When we -- the data was a little bit lower efficacy than Dupixent, but that's like a simple comparison that someone like me would do. So maybe you could give us a little bit of more context on the elements of safety, efficacy, dosing profile that give us to understand the ultimate profile of the product.

Thanks, Richard. Firstly, I'm rarely commented on my sartorial elegance. So I appreciate the notice. I'll try and keep up.

Very rarely.

Very rarely. I'll try and keep it up.

Same for me as well.

Two, COAST 1 and amlitelimab. I think that take a step back, the unmet medical need in atopic dermatitis remains. We have in partnership with Regeneron an excellent molecule in Dupixent, but it's an area of huge biologic eligible underpenetration and the more molecules we can bring in and options for the patients, especially for other molecules from which there is substantial switching, I think, leaves a lot of value for patients on the table point one. How does Amlitelimab address that with a novel biology of the OX40-Ligand pathway, which has a broader coverage of TH2 in innate immunity. I think we had always been hopeful that it would be interesting contribution to patients. We had always been super clear that because of its impact on T-cell biology, we take a bit longer to get to the lofty heights of efficacy. But we always anticipated that it would continue to improve over time.

So what do we find on COAST 1? We found that it was a molecule that hit its primary endpoint as expected. It continued to get better from 16 to 24 weeks. The posology was excellent. What I mean by that is both at Q4W and Q12W, we had a really good result. All of those speaking to the value for patients. And finally, when you asked about safety, we were clear that the safety profile is entirely consistent with the safety profile that had been anticipated at the inception of the acquisition of the molecule from Kymab and onwards.

What do we have to look forward to, I think that we remain infused and hopeful that COAST 2 will replicate many of those features of the molecule. My own preference is, of course, that we hit the primary endpoint as we did in COAST 1, that is obviously the most important thing. But actually, we retain the posology, et cetera. And then I want to recognize that COAST 2 is an entry ticket filing and submission. But actually, as we build the momentum around amlitelimab and specifically around SHORE, I think that what we'll be able to do is -- and throughout the year with ESTUARY, AQUA, HYDRA and others, we'll be able to begin to convey a, to the community that we have a drug that continues to improve in efficacy over the year, beyond 24 weeks. And secondly, and perhaps equally and perhaps more importantly, commercially, the combination early with corticosteroids, topical corticosteroids, et cetera, is something that amlitelimab will exhibit.

Any differences in terms of the COAST 2 patient population that could have something slightly different in terms of COAST 1. Obviously, we'd expect it to be successful. But any differences there in the trials, what's recruited that could give us a different result?

Yes, broader point is that lessons learned by us and others in immunology over the last year have made it very clear that molecules that go into areas with established standard of care, make those clinical trials more complicated, both in placebo response, et cetera. So we have to be measured and thoughtful about that, and we'll keep our eye on placebo response rates, et cetera, which I think what you're alluding to. There are no meaningful differences in recruitment strategies that were -- that we anticipate will in any adverse way direct the outcome of the trial.

Yes. I think maybe it's also worth adding that if COAST 2 is -- reads out exactly the same as COAST 1, we have a Q12 in AD, which is going to be a huge deal for patients who really particularly naive patients who don't want to get into an every 2-week injection environment. The thing about this is as more drugs have launched, and you've seen this Dupixent actually accelerates in its growth in volume as more medicines come in because biologic penetration is so low in AD. The more drugs come, everybody, all boats rise. There is a potential for a small group of patients to come off drug and be in disease remission.

And that's another reason why it will be used widely in the naive setting because some patients will always ask, am I going to be on this for the rest of my life? Well, for some they'll be able to come off it. Not a lot, but enough to be meaningful to make that choice. If we deliver that and the increasing efficacy profile out through 48 weeks, then I think we're going to find ourselves with one of the most important medicines in AD. And so fingers crossed for COAST 2.

Yes. And ESTUARY, you highlighted the idea of increasing efficacy with time. What gives you the confidence in that you might see that in ESTUARY?

I'm going to try and walk it back and make sure everyone understands that we will have COAST 2 and SHORE coming. I said that in our late-stage pipeline review on the 16th of December, we will continue that process. Just to give you guys a red thread of where we're going, I think SHORE is extremely important, and I would in-depth on SHORE as a combination of topical corticosteroid therapy. And then the second point is, I think it's important that we don't over crystal ball, the likely outcomes beyond 24 weeks, up to 52 weeks. What gives us confidence, though, is the biology of amlitelimab. As you energize T cells that encounter their cognitive antigen throughout the life cycle of dosing, I think you'll see that, that efficacy gets better, and we hope to not only give you insights through AQUA and HYDRA this year to biologic inadequate responders, but I also hope that through ESTUARY but also some of our open label studies, you'll get a better sense of improving efficacy.

And Paul, you touched on the growth of the market with new mechanisms, multiple mechanisms. You've got amlitelimab with positive Phase III. How do you think about developing the wider portfolio in AD because you could address in different mechanisms, lots of those. So do you add to that portfolio? Is that something that you'd be thinking about?

Well, we just -- I think it was announced today about our STAT6 going into the clinic for the first time. I think we look at other master switches that we think could do things with different ways of administration that patients want the choice. And if we can provide that for them, we will. Not everybody is perfectly treated and you know in AD and in psoriasis and these other areas, people go from very difficult disease burdens to 90% clear skin. And then they start to get disappointed that it's only 90% and then they start moving between mechanisms. It's always been like that. These are highly symptomatic, highly motivated patients why I love these areas.

And so consequently, we're open-minded about adding new mechanisms. We have bispecifics that we can take into AD. And we have multiple shots in GI. We have multiple shots in asthma and hopefully COPD, because we understand that dynamic that as more medicines arrive, the market expands significantly. This is not a saturated market. It's the absolute opposite. And so it is worth having new things because patients are ready for them and that gives us huge opportunity.

Yes. Just to build on that, Richard. This time last year, you asked me -- throughout the year about the relevance of our bispecific platform in atopic dermatitis. There was a question that you were very interested to discuss and I think there was some perhaps minor skepticism about the role of lunsekimig in atopic dermatitis. Well, the ball is sort of caught up with us. In that last year, we thought we had an asymmetric insight into the role of TSLP in atopic dermatitis. I think there were people who questioned it based on the Teze data. I'm very pleased to announce that wholly internally generated R&D insights encompassing the role of IL-13 and Teze -- sorry, TSLP in atopic dermatitis came from Sanofi. We created the molecule.

We -- as an R&D organization that was responsible, took a measured risk into atopic dermatitis and just late last year, there was another molecule TSLP -- long-acting TSLP molecule went into atopic dermatitis that showed early efficacy in Phase II. I think that begins to demonstrate that not only does Sanofi has asymmetric insights, we through thoughtful portfolio allocation, take the appropriate measured risks to give us breakout value. And we will have the results of that in the near future.

Interesting. And maybe thoughtful portfolio allocation, duvakitug is obviously a little bit behind others, but a very small capital outlay from you guys, but actually could have one of the better profiles as well. So maybe you could put into context for us what we're going to see on duvakitug, how you see the profile as is developed thus far and where we go with that?

Yes. So duva is very interesting. And I've often said, we've talked about this. It's a sleeper in our portfolio. And the reason it's a sleeper is that we said at the very beginning, we had the best -- we thought we had a real chance of having the best molecule, both from a biophysical perspective but also with its impact on the Decoy 3 receptor and I was quietly bullish about that early on. The ECHO data in 2025, both in UC and CD confirmed that we may have not only the best-in-class molecule, but potentially, and we should be sort of completely thoughtful about how we convey this potentially best-in-disease molecule.

Let's see whether the maintenance data plays out, that comes later in the year, but that would be pretty exciting. I think that has the potential not only to transform common or garden IBD if such a thing exists, but also in populations in whom safety has become a relevant issue. I won't talk more about those. The only thing I will say is that you pointed correctly to the view that we increasingly will have to use our proven development muscles to ensure that we position duvakitug correctly against its competitors.

Excellent. And maybe turning to MS and frexalimab, maybe thoughts on that because data on lesions was very strong. How do you see that translating both in terms of disability progression, but also ARR, which has been a more challenging end point across the space these days?

So just a first comment, then I think the -- as I reflect on our year last year, I think that we showed you a interface of some complexity, real commitment to the patients with MS going forward. We remain committed to these patients. For Sanofi, obviously, we are entirely thoughtful about our shareholders, but what we did with MS last year demonstrates our unequivocal commitment to patients, point one. And I think first and foremost, it's the only thing that gets us up in the morning or at least the first one. So that's our thoughts are with MS patients.

Number 2 is, I think the data speaks for itself. Our secondary progressive data was striking, and we await some regulatory decisions later this quarter for tolebrutinib. And then more broadly, your comment about endpoints in MS, we've been entirely consistent. I think, that we've said that ARR was a very convenient measure over the last 30 years, but increasingly, disability will be important. And for all of our molecules, whether it's tole or frexalimab and otherwise, we've ensured that we remain consistent with the views of the past with ARR. We look forward to the future with disability.

And specifically for frexa, safety of the molecule versus efficacy, just thoughts there.

Yes, there's no -- and there's multiple CD40 pathway modulators out there. The theoretical considerations with respect to risk, which are minor have actually not played out. So touch wood, and with the recognition that we're midway through trials, we don't have any signals that we're concerned about.

Okay. Maybe in the last few minutes, we could just pivot maybe to some of the new launches that were on your initial slide, Wayrilz, the COVID vaccine. I'm not even going to attempt the -- I can't even remember the brand the -- anyway.

Fitusiran.

Indeed, you know where I'm going. So yes, thoughts on those progression of the launches, how they're doing, what we should think about them contributing to the growth?

We've been extremely effective our launches. We've -- you look at Beyfortus, you look at Altuviiio. We've really, I think, surprised a lot of people with just how effective that we've been. Wayrilz, I'm not going to share the data because it's still early, is ahead of our expectations. And that's kudos to the team and everything that's being done by Brian and his guys. Wayrilz is -- and it's just getting started given the number of indications that it's going to have. So we're very happy with that. Qfitlia, fitusiran in hemophilia is a much slower start, but completely as anticipated because this is like a very specific tailoring of the medicine to each individual, but it is a true every 8-week dose for people with hemophilia. This is life-changing moment.

So slow and steady as people get up to speed with how to administer, but we're very encouraged by that, too. So in general, I think our commercial engine and our late-stage development and the team and regulatory on the labels have done extraordinary job because we're really able to go and get share and to really land with some substance commercially. The question remains, can we bring duvakitug, amlitelimab, lunsekimig? Can we provide data this year that gives people the confidence that we have $2 billion, $3 billion, $4 billion, $5 billion medicines that are coming behind to put in this excellent launch machine.

Makes sense. And Ayvakit going well as well?

Yes. Yes, really well. I mean it was -- as I mentioned it upfront, but -- it's a year ago since we began those conversations with Blueprint. I look at how deals are being done now and premiums being paid. I think we paid around 30% premium. We paid exactly what we'd hope to pay and we inherited a medicine that is really positively surprising everybody that was early in its launch phase. That profile for us, which means it continued to grow through Dupixent LOE and the fact that it has a follow-on elenestinib and the fact that it has a wild-type shot also in immunology, further back in the pipeline, made the profile a perfect overlay for us. Very happy with the Ayvakit performance. And again, Brian and his team how they've been integrated and how they kept the momentum is great.

Makes sense. And Francois and you did talked about -- Francois talked about Dupi being 1/3 of the growth. On that 1/3, how is that going in terms of the new launches, CSU, COPD. It's smaller part of AD. AD will -- as we've discussed multiple times, will grow for a very long time. But what's the growth outlook there?

Well, the growth is incredible. This what we -- 8 -- 7, 8 years in, and we're growing close to 30% on a drug that was over $4 billion on the quarter. This is incredible work by the team and incredible work on choosing the follow-on indications. It will slow a little this year from that heavy height because, of course, we've anniversaried COPD, CSU. So we're realistic, but it will still be the dominant player, and it will be growing until its very last day. It's one of those rare combinations of medicines with extraordinary efficacy and extraordinary safety to launch first in class. That's why new mechanisms, new lengths of treatment, possibly for remission. That's why those things are what physicians want now for the -- for naive patients, but Dupixent is going to run hard right until its last day, very proud to be involved in it. And the growth rate is really incredible.

And your partner showed a little bit of color maybe on that last day in terms of next-generation products or long generation. Just is there any color on that last day from a Sanofi point of view?

Well, we -- depending on our own assumptions are a minimum of 2031, 2032 for Dupixent. If we take IPD as a sort of consensus, we're more likely 2033, '34. That far out, it's not always good to overshare what you plan to do because there are plenty of companies that are waiting for a hint, so they can then operationalize what they want to do to disrupt what we plan to do. I'm well aware though, given the setbacks we had last year, the scrutiny around the Dupixent LOE and how we manage it has perhaps been brought even further forward. I know Len and the team have started to share a little bit of our philosophy and I think 2026 is the year where we're going to be much more open about our intentions on how to manage Dupixent effectively for patients. And also, what might be the opportunities around it and after it that we can do with our great partners Regeneron.

Makes sense. Maybe 2 other growth questions. ALTUVIIIO has had a -- and was mentioned on the slide is going to be near blockbuster or blockbuster. Yes, I mean there is more competition in the same area as Hemlibra launching at the end of '26. But how much more room to go is there with ALTUVIIIO, I suppose, is the question?

Well, I think the market is sort of split, right? For a long time, it was 3 infusions a week. Then you have the options with Hemlibra to be monthly and sadly, many of those patients ended up weekly. ALTUVIIIO came and gave people a normal annual bleeding rate at a weekly dose. And that gave people the opportunity to deliver a normal life particularly young adults. And while it didn't sound s***, certainly remember reading one of your notes, well, it didn't sound s*** at the time. The fact that it's going on to be a blockbuster is a sort of affirmation that living a normal life even at a weekly dose is a very credible aspiration for patients. And we've seen that pulled up very clearly. There's going to be new entrants on monthly. Qfitlia is every 8 weeks. And we're going to see the patients sort of split between, do I want the most convenience or do I want to live the most normal life. I think even with the new monthlies that are coming, their ABRs are not 0. So we just have to recognize that those trades will be made. Lots of opportunity in the factor market and beyond for ALTUVIIIO.

Fantastic. Maybe last question, just returning to Beyfortus. We talked about some of the pressures in the U.S. You highlighted the very strong efficacy. Maybe you could talk about how that strength of efficacy brings new countries on board and patients ex-U.S. and the growth potential there because while the U.S. is big, the world is quite a lot bigger. So how do you -- that's really insight from me by the way.

So I think what surprised everybody about Beyfortus was for health care systems, it was a current fiscal year payback. It's a premium-priced vaccine approach, even though it's a monoclonal antibody and that meant that access was reached -- within reach for almost every baby that needed a protection. What surprised people next was the data accumulated so fast. We spent a lot of time perfecting the real-world evidence data so that payers could look and make a decision very quickly. If you invest in protecting babies with Beyfortus, you will avoid significant costs this year. Now with health systems under pressure financially, current year paybacks are a gift to health systems. And that's before we even get to babies who are protected, babies who can avoid some very difficult days in the ICU. So I think people saw very quickly. If you look at our revenue and how quickly it became a blockbuster, it's the most successful pediatric vaccination launch in the history of vaccines.

So people see it as incredibly effective. The real-world evidence that has been accumulated showed that it absolutely pays back within the current year and protects those babies. And that is just a gift to parents, but it's also a gift to health care system. So we have work to do. There's competition. We think our half-life guarantees us to protect the baby for the entire RSV season. We think we may be wrong that the competition doesn't offer that. We'll find out. But we've accumulated so much real-world evidence data. It's quite difficult for others to demonstrate this data set we have at launch because we're in great shape on Beyfortus.

Perfect. Thanks very much, Paul. Thanks, Francois. Thanks Houman. Thanks, everybody.

Thank you.

Good afternoon and good morning, depending on where you are, and welcome to the Sanofi's first year-end late-stage pipeline review. I'm Thomas Kudsk Larsen from the Investor Relations team and I'm pleased to see so many people on the call today.

Before we get started, I want to thank Elise and the IR team for leading the work on today's call. I also want to remind everyone that our focus is on the clinical and regulatory aspects of the mid- and late-stage pipeline. So we will aim at keeping any commercial or finance questions for another day. We want science and patience to take center stage.

During the call, we'll highlight the most important events in 2025 across our pipeline in immunology, rare diseases, hemato-oncology, neurology and vaccines and provide the key news flow items for the first half and the second half of next year and 2027. Because a couple of 2025 news items deflated expectations, we believe that next year's news flow comes with lower anticipation in general. The presentation will take about half an hour, and then we take your questions. As always, the presentation is available for download on sanofi.com.

Please turn to Slide 2. Here, we have the usual forward-looking statements. We would like to remind you that information presented in this call contains some forward-looking statements, which are subject to substantial risks and uncertainties that may cause actual results to differ materially. We encourage you to read the disclaimer in our slide presentation. In addition, we refer you to our Form 20-F on file with the U.S. SEC and our French universal registration document for a description of these risk factors.

Please turn to Slide 3. Today, we are joined by Houman, Head of R&D; and Jean Francois, Head of R&D for Vaccines. Before I hand over to Houman, I want to thank everyone on the call for the interest in Sanofi and for your support during the year. It has been a busy year with news, some favorable, some unfavorable, and there are lots of changes in the world around us. However, as you will hear today, we are focused on moving forward with our pipeline-driven transformation.

With this, I'll now hand you over to Houman.

Thanks, Thomas, and thank you, everyone, for joining us today. It's a pleasure to be with you to discuss the medicines and vaccines that we are most focused on in our pipeline. After a big welcome from my side to Jean-Francois, who will cover vaccines a little later. Now over the past 2 years, we've made multiple new appointments across key functions in R&D. New hires include heads of development, translational medicine, digital research, regulatory affairs and a new Chief Medical Officer. We focused on building a skilled and thoughtful R&D experience leadership team, perhaps the best in the industry, combining internal expertise with external talent to drive innovation and change how we approach R&D and Sanofi. I'm pleased and proud to work with his team and the teams that they serve to advance our science and our pipeline further.

Please turn to Slide 4. As we refine the way we work and build a sustainable pipeline for the future, we've also defined several key performance indicators to track our progress. For Sanofi of the future will have a rigorous science-based culture, and therefore, we are looking to scientific publications as one important leading indicator of progress. Scientific publications and top-tier channels reflect the quality and impact of Sanofi's R&D programs and strengthen the company's position in the scientific community.

In parallel, we have seen an increasing trend for patent filings across our 4 main geographies, and we reached an all-time new high in 2024, the latest full year available. Patent filings demonstrate innovation across all major biopharma modalities, showcasing platform diversity and technological breadth. Other leading indicators include regulatory designation. For a few quarters, you have already been able to track those in the appendix to our quarterly results investor presentation.

Please turn to Slide 5. Ultimately, we're in the business of improving public health, and there's no better way of doing that than bringing innovation to patients in the form of new medicines and of course, vaccine. In 2025, Capitalia became the first RNAi or an interference antithrombin medicine approved for hemophilia A and B in the U.S. and China, representing an innovative mechanism of action in hemophilia treatment. Way Reals received approval as the first BTK inhibitor for ITP in the U.S. with regulatory reviews going on in Japan and China and a positive CHMP recommendation in the EU from October for this rare blood disorder, and Nuvaxovid achieved full approval as the first recombinant COVID-19 vaccine in both the U.S. and EU, providing an important non-mRNA option for COVID-19 prevention.

Slide 6, please. In addition to the approvals, we have several Phase II and III readouts in the pipeline across immunology, round disease, oncology, neurology and vaccines. Importantly, amlitelimab met primary and secondary end points in the first Phase III study of atopic dermatitis COSI demonstrating clinically meaningful improvements in skin clearance and disease severity and intriguingly promising potential for quarterly dosing.

It's [indiscernible] primary Phase III endpoint in NARIFY-1. One of the 2 studies informsmokers with COPD showing significant reduction in moderate or severe exacerbations. However, the second study did not meet the primary endpoint, handing us a mixed outcome overall. Efdoralprin alfa met all primary and key secondary endpoints in alpha-1-antitrypsin deficiency emphysema and demonstrating superiority versus standard weekly plasma-derived therapy. Tolebrutinib did not be the primary endpoint in pesos in primary progressive multiple esterases but remains under active regulatory review in secondary progressive disease where you could potentially become an option for patients with limited access to approved medicines today. Multiple vaccine candidates showed positive safety and immunogenicity results, including SP 0087 for raves prevention and combination of vaccine SB-27, for influenza and COVID-19 and SB0289 for pandemic preparedness.

As Thomas mentioned earlier, not all news items are favorable in 2025. It's important to recognize this, but also assure everyone that we're learning from the challenges we are faced with. For example, we're continuously and adaptively adjusting ongoing study with learnings from PAR studies. Biopharma development is inherently a risky business with a high potential rewards, which means we fail, learn, move on and ultimately succeed.

Slide 7, please. We'll now take a closer look at the pipeline achievements in 2025 by disease area, starting with immunology and Dupixent. During the year, DUPIXENT received U.S. approval for bilipanphagoid with the regulatory decisions expected in the EU, Japan and China in the first half of next year, expanding the dermatology franchise into rare autoimmune blistering diseases. The Liberty Cubic Phase III program successfully reported approval for chronic spontaneous urticaria in the U.S., EU and Japan, providing a new regulatory option for patients with this challenging condition. In China, the regulatory submission is anticipated in the first half of next year. The LIBERTY AIMS Phase III study demonstrated that DUPIXENT clinically meaningfully improve radiographic and the topic and symptom measures in allergic fungal rhinusitis patients. A U.S. regulatory decision is expected in the first half of next year. We're very proud of DUPIXENT, but of course, there's a lot more to Sanofi than Dupixent. So let's move on.

Slide 8, please. Staying on immunology and now looking at how we can further augment the value we bring to patients in dermatology beyond Dupixent. amlitelimab, our OX40 ligand moleculal antibody targeting the fundamental immune node and TNF [indiscernible] ligand, is intended to mitigate the impact of multiple different disease pathways at a different points in disease drive the heterogenous disease that is atopic dermatitis. Amlitelimab demonstrated clinically meaningful improvement in skin clearance and disease severity in atopic dermatitis. While amlitelimab mechanism of action increases over time, the COSI Phase III study show progressive efficacy increases with no plateau yet observed and some secondary endpoints like each which also showed early benefit. It also is the potential of patient-friendly, quarterly dosing that reduced the treatment but, no new safety burdens were identified in this study. In addition, brivekimig, our TNFaxOX40L nanobody conceived of and generated entirely within Sanofi achieved its primary Phase II objective in hidradenitis suppurativa with clinically meaningful improvements in high school 75 responses compared to placebo.

Owing to the quality of the data and enthusiasm from the community Phase IIb study for rebecamig is commanding patients who evaluate -- to further evaluate the efficacy and safety profile across different patient populations and disease severity. Amatilumab and Bravecmig are expected to deepen Sanofi's presence in dermatology, broadening in atopic dermatitis and entering skin diseases such as HS, an area of large unmet medical need adjacent to atopic dermatitis.

Next slide, please. Moving to respiratory. Our second biggest arrinimmunology amitilumab showed hypothesis generating Phase II efficacy in difficult-to-treat asthma with heterogenous inflammation characterized by his intervals and elevated neutrophils. Notably, this timely also serve to confirm the interval dosing we see in atopic dermatitis. In this study, based on our post hoc analysis, we estimate this subgroup is about 1/5 of the total asthma patient. The next development steps is subject to a full understanding of the unmet medical need portfolio prioritization and ongoing regulatory discussions to determine the optimal development strategies across the pipeline. I continue to extol the virtues of dynamic capital allocation and careful financial stewardship driving value creation, which I advocated from my very first day here.

Itepekimab achieved a significant 27% reduction in moderate or severe COPD exacerbations in AR1 Phase III study, but did not meet the primary endpoint in ARII. Given the unmet medical need in COPD, and the setback by other companies in this field, we're considering our strategy, including through ongoing discussions with our collaborator and partner Regeneron as well as regulatory authorities, and we will communicate progress in due course.

Slide 10. Staying in respiratory, lunsekimig is a pentavalent nanobody, the multispecificy to both TSLPML13 at 2 unique epitomes with additional human serum albumin binding to increase half-life and potential enhanced efficacy. Previous Phase Ib data in mild to moderate asthma showed a rapid and significant reduction in pheno levels at day 29, indicating meaningful anti-inflammatory activity. Biomarker reductions were observed across Sinofi, our 5 [indiscernible], IGE and Tak with improvements in FEV1 and small airway function in patients with impaired lung disease.

Phase II studies are underway in asthma, COPD atopic dermatitis and chronic ramucitis with NP with the first Phase II readouts expected in the first half of next year. As we advance bispecific Nanobody molecules, it's important to remember the platform has already demonstrated clinical and regulatory validation with Cablivi medicine for acquired and our Rare franchise.

Slide 11. Moving to new areas of immunology. Balanton firm are oral TNF small molecule TNFR1 signaling inhibitor showed not only significant efficacy in Phase II studies for psoriasis and rheumatoid arthritis with more encouraging results on endpoints reflecting deeper disease control. The inhibitor was generally well tolerated, and we currently see potential monotherapy in RA subject to further evaluation as well as combination and backbone with other oral medicines with the next steps currently under evaluation.

[indiscernible] antibody not inhibiting the DKI receptor at all primary endpoints with a competitive profile and week 14 in Phase IIb studies for [indiscernible] disease and ulcerative colitis, demonstrating efficacy across inflammatory bowel disease. The data were presented earlier this year. The molecule and leading endoscopic response rates in Crohn's disease compared to other TL1A class molecules, positioning it competitively in this area. Phase III studies of duvakitug recently commenced with subcutaneous dosing in both UC and Crohn's disease, the unmet medical need in IBD is if anything, increasing and Sanofi is committed to making a difference here.

There are 4 more diseases to cover today. Slide 12. Leading immunology, we're now moving on to rare disease and oncology. Wayrilz is now approved in ITP in the U.S. and under regulatory review in Japan and China and the positive CHMP recommendation in the EU from October and with orphan designation in multiple regions, reflecting its importance for [indiscernible]. Phase II data in IgG4 disease showed a considerable reduction in disease flares as well as being glue corticoid sparing with a Phase III study planned to start based on these encouraging reasons. Phase III studies have already been initiated in warm autoimmune hemolytic anemia based on exploratory Phase II results showing clinical benefit and sickle cell disease based on clinical evidence. This medicine represents a potential new multi-immune modulation platform with disease-modifying potential across multiple autoimmune conditions, expanding beyond the initial ITP indication.

Slide 13, please. Staying with the intersection between IMI and rare diseases and based on the strategic acquisition of Blueprint earlier this year, Sanofi building a leading franchise in mastocytosis with elanetanib as a potential next-generation the 816 KIT inhibitor in Phase II/III development to follow on from [indiscernible]. In addition, BLU-808 is being assessed as a highly potent and selective wild type KIT inhibitor in Phase II, leveraging BLUEPRINT expertise in kit and [indiscernible] biology. This has been a challenging and high-risk target from a TI perspective for the industry, but with a world-class expertise of our Blueprint Sanofi colleague, this will represent 1 of our approaches to the increasingly recognized role of mast cells in disease. Efdoralprin alfa, recombinant AAT protein demonstrated superiority versus weekly pansmen-derived therapy with Q3 and Q4 dosing in alpha antitrypsin deficiency emphysema patients. The Phase II study met all the primary and key secondary end points with statistically significant superior functional AT truck level at week 32, supporting potential for less frequent dosing with a regulatory submission planned for the second half of next year.

Slide 14. Following solid clinical progress last year, SARCLISA continued to deliver for cancer patients in 2025. So less subcutaneous formulation establish noninferiority to IV administration in relapsed refractory multi-myeloma in the IRACLEAR-Phase III study, providing patients with a more convenient treatment. Further policy data have been generated across multiple regimens, including combinations with VRD and the newly diagnosed trial farm eligible and transplant ineligible patients expanding treatment options across the used agents. For eligible patients, the subcutaneous formulation demonstrated a similar safety profile to IV with no new safety concerns. And most patients and providers prefer the automated hands-free delivery system. Early combination strategy and subcutane administration unlock significant benefits for patients with multiple myeloma, representing very successful life cycle management and execution by our hemato-oncology colleagues. Slide 15. Moving to neurology now, we have 2 main projects in late-stage development, tolebrutinib, our second BTK inhibitor and frecalabat. Tolibrutinib demonstrated a convincing 31% delay in time to onset of 6 months confirmed disability progression in secondary progressive multiple sclerosis, representing meaningful clinical benefit. We saw about a 4% rate in patients with elevated liver enzymes over 30 limits of normal. -- all within the first 3 months starting therapy.

In short, this is a benefit risk equation that we navigate on tolebrutinib in the SPMS set. And primary progressive multiple sclerosis, calabrutinib did not meet the primary endpoint of composite confirmed disability progression in purses, Safety was consistent with previous studies -- based on this result, we will not pursue regulatory submission in this setting. In SPMS, we anticipate a regulatory decision in the U.S. and in the EU during the first half of 2026. [indiscernible], second-generation Fc-modified CD40 ligand antibody blocking both innate and adaptive immune responses via the costimulatory CB4 power previously showed a large reduction in new GA positive T1 lesions at week 12 in a Phase II randomized RMS study with sustained reduction through week 96. The study was published in New England Journal. Phase III studies for fretelumab in RMS and STMS are ongoing with readouts expected in 2027.

While there were no significant clinical developments with fraxalimab in 2025, we wanted to remind everyone of our commitment to patients with MS. I mentioned that we expect all earnings from tolebrutinib and other MS medicines in development will help us strengthen the clinical program francelimab ahead of the anticipated data readout in 2027.

Please turn to Slide 16. During the year, we shared updates on ridiprubat and CIDP. Patients treated with complement C1 inhibitor showed a 35% reduction in neurofilament light chain levels with strong and sustainable reduction of complement activity from baseline indicating target engagement. As previously reported in 2024 at 24 weeks, 87% of standard of care patients improved or remained stable after switching from their previous treatment to really prove out. As reported this year at 76 weeks, 80% remained relapse 3, staying on [indiscernible]. For the second treatment group, the standard of care refractory patients, 89% improved, will remain stable, we really prove at 24 weeks, the number of 76 weeks, which commensurately 78%. And last, for the third group of patients, naive patients, the corresponding numbers were 92% and 86%, respectively. Across treatment groups, this shows a solid durability of the treatment effect. The comprehensive subcutaneous Phase III program INCLUDE II study, vitalize the first head-to-head study, patients who are on IVIG and remain partial responders and mobilize the study for standard of care refractory patients, which means patients who have experienced failure or inadequate response, standard of care therapy, which is IVIg or steroids depending on the jurisdiction. We look forward to the Phase III study readout from this comprehensive program in '27. In addition, a study is also underway, an antibody mediates rejection with orphan drug designation in the U.S., expanding the potential of complement inhibition beyond neuro inflammation.

Please turn to Slide 17. And with the greatest pleasure, I hand over to Jean-Francois.

Thank you very much, Houman. Hi, everyone. I hope you're doing well and warm at the end of this year. So it's now my pleasure to take the next 5 minutes to cover the progress that we've made in our vaccines pipeline. So as you all know, Sanofi has established a strong legacy in influence vaccines, and we've recently expanded into broader respiratory disease prevention, including RSV and COVID-19. There, we obviously leverage the expertise and the platform that we have developed [indiscernible] case. In the middle, as we speak, we before now protected over 10 million infants across more than 40 countries. In [indiscernible] evidence before this has consistently demonstrated about 80% reduction in hospitalization and it has allowed Sanofi to establish a leadership position in RSB prevention. [indiscernible] on this slide represent the first recombinant COVID-19 vaccine with full approval in the U.S. and in Europe, and it offers health care providers and patients with an important alternative to marine base vaccine, obviously.

When you look at the next project in our pipeline, you see an important pneumococcal vaccine in Phase II combination vaccines for influenza cabin, Pandemic properness solution for H5 influenza and other combination approaches using both mRNA and non-M&A platforms to address diverse respiratory threats. We'll now go deeper into this year's achievement, first in influenza and COVID-19 and then in respiratory disease.

Please turn to Slide 18. So this year, we have released unity iDose Phase IV study data. This trial represents the world's largest influenza vaccine randomized effectiveness study with 466,000 old adults across 2 countries, Spain and Denmark and 3 [indiscernible] seasons. The study has demonstrated superior protection of high dose versus standard dose infant vaccine against hospitalization endpoint in the older adult population, supporting again the excellent clinical value of [indiscernible]. In the middle, you see that we have achieved positive Phase II results for both of our Influenza plus COVID combo vaccine, combining either [indiscernible] or Flublok with [indiscernible]. These results support a high probability of demonstrating noninferiority in Phase III studies that would compare the new vaccine against the widely used regimen with flu and COVID-19 vaccine are co-administered. You also remember that we decided 4 years ago to invest in mRNA technology to enhance our readiness for the next pandemic.

This year, we are very pleased to see that our H5 pandemic influenza mRNA vaccine showed 93 seroprotection rate across both age group. -- basically the 18 to 64 years adult and above 65 years of age adult. And this was achieved after the classic interaction regimen and at the lowest dose that we tested. These data not only support the competitiveness of our proprietary mRNA platform, but also show how we have improved our pandemic readiness. So building on our solid pipeline progress in inference and COVID-19. Let me now cover the progress we have made in other respiratory diseases. And please turn to Slide 19. So here, I'm going to cover mainly RSV plus HNPV. And you remember that our strategy to enter the RSV older adult vaccine market has been to develop a bivalent [indiscernible] plus HPV vaccine that would double the medical value for public systems and patients compared to the vaccine available today, which is RSB standalone vaccines. So this year, as you can see on the left part of this slide, we got the clinical evidence of the competitive performance of our RSB mRNA component, which we believe will be in line with competitors. So what you can see on the left table is that our monovalent RSV mRNA vaccine showed high efficacy on several endpoints in the Phase II study, including 75% vaccine efficacy against RSV LTD at a median follow-up of 5.5 months.

And actually, we also would have a predicted 100% efficacy if we were to use similar Phase III end points as our competitors. So let's now have a look at the HPV component in the middle [indiscernible]. And there, you can see that a bivalent RSP and HMPVMRN vaccine induced very competitive HMPV antibody level in a Phase I/II study. And again, this was achieved with a bivalent vaccine. And finally, as you know, we also recently closed the acquisition of [indiscernible], and I'm very pleased to show you on the right panel for the first time that Vicebio bio bivalent RSV and HPV vaccine showed up to 15-fold increase in our neutralizing antibody levels and severalfold increase in HMPV neutralizing antibody level in the small Phase I conducted by Vizio. So basically, this validates the recent acquisition of the company, the molecular plant technology that they have developed and the addition of this vaccine candidate into [indiscernible]. So as a next step, we plan to initiate next year, the Phase II study for the bivalent parts and PV vaccine candidate from [indiscernible].

Please turn to Slide 20, and I hand back to Houman.

Thanks, Jean-Francois. Super clear and a great year for vaccines. Before we close the presentation, we wanted to cover the important topic of pipeline replenishment and new technology. We can replenish from Insight Sanofi, and we can augment with external opportunities through business development, licensing and acquisitions as we saw earlier this year with both Blueprint and Vicebio. Seven new molecules have been added to the Phase I development, including [indiscernible] specific antibody, a TREM2 agonist GPRC5D antibody, showing continued innovation across multiple modalities. Based on Sanofi's capabilities in genomic medicine, free AAV gene therapy programs enter Phase I 1 in dry AMD, 1 in myotonic distri type 1 and 1 in wet AMD already having progressed rapidly to phase II. The GranBio acquisition earlier in the year provided CD20-directed myeloid cell engager just mentioned with the potential for targeted phagocytosis and B-cell depletion to reset adaptive immunity. .

Also, new external partnerships have been established with recludix and Arendal labs to access novel targets, including STAT6 inhibitors and dual targeting antibodies, supplementing our internal innovation efforts. The STAT6 inhibitor will advance to Phase I very soon. As we forward -- as we move forward, internal research and early development efforts supplemented by external innovation will further replenish and strengthen our early-stage pack.

Please turn to Slide 21. On new technology, Sanofi's new digital R&D plans target more than 40% reductions in overall development cycle times from research through to approval across the entire value chain. It is an ambitious target for the next handful of years, but if we succeed, it will represent a much improved approach to drug development and a significant boost in productivity.

The initiative spans drag discovery and design, clinical development, regulatory processes and approval launch revise activities, ensuring end-to-end optimization of the development process. Current development timelines include about 4 years for research, 18 months of preclinical research, 7.5 years for the clinical phases and several months for the dossier preparation and ultimately, registration. Digital transformation will help accelerate this innovation and bring new medicines to patients faster while maintaining scientific rigor and regulatory compliance standards.

Please turn to Slide 22. Summarizing all key development projects, the immunology portfolio includes multiple Phase III programs with amylitelamab and atopic dermatitis, [indiscernible] IBD, itepekimab in COPD -- and with the outline caveat, all representing significant opportunities to expand our presence in immunology. They are followed by Phase II program for the bispecific in HS, asthma and other areas of immunology. Neurology programs still feature to brand SPMS, brexalumab in RMS and SPMS studies and riliprubart in Phase III CIBP studies addressing higher unmet medical need patient. The rare disease and oncology portfolios include Sarclisa with its subcutaneous formulation submitted, we reels approved for ITP with life cycle management potential and multiple programs for [indiscernible] disease and Fabry's disease. -- the vaccines portfolio encompasses Phase III programs or flu zone high dose in adults 50 years of over, SP0087 for [indiscernible], SP0202 for pneumococcal disease in children and face the Phase II programs for RSV, combinations and pandemic influenza. We continuously review the pipeline and seek to allocate our resources and R&D investments into the opportunities that add the most value for patients and for the company. As a result, you will see changes from time to time. While there are projects being started and terminated with a next update with Q4 results in January, the pipeline shared here today is the pipeline we will take into next year.

Turn to Slide 23. As we look ahead, we're now providing the news flow in the for the first half and the second half of next year and by 2027 for the first. In the first half of next year, regulatory decisions expected across different regions to depict on fair, AFRS BP and CFS children, teplizumab lifecycle and Sarclisa subcutaneous [indiscernible]. First half clinical data readouts include more amlitelimab data in AD lensecomigan asthma and multiple opportunities in rare disease, including gases and Fabris with a venglustat, potentially offering new opportunities for these patients. Second half of next year offers more data from the Dupixent life cycle program and regulatory submissions of data from the first half and earlier, potentially including [indiscernible] per AATD. 2027 has several Phase III readouts, including data for regulatory submission, but [indiscernible] outside the U.S., reclimb in RMS really creating CIDP and multiple vaccine programs, including SB0202 in pneumococcal disease anticipated to sustain long-term growth momentum.

As we move ahead with our pipeline, more news items will be added both from our internal efforts augmented by business development opportunities, we are committed to a sustainable pipeline to take an before Sanofi. Before we close, our summary outlined the progress in building R&D capabilities and advancing our pipeline. The leadership changes we've made across research development and other key R&D functions strengthen our organization. Our 2025 approval can fill away rules and eval demonstrate progress on bringing innovation to patients. Life cycle management options for Dupixent, cycles and influenza vaccine are important for expanding the clinical benefit. For example, we hit the mark of 1.3 million patients treated with DUPIXENT in 2025. Our Phase III programs have matured during the year, including ablitilumab, [indiscernible], while important by specific nanobodies, advance further into mid-stage development.

In '26 and '27, across biopharma and vaccine, we're currently expecting more than 15 regulatory submissions, more than 30 new regulatory submissions sorry, about 15 regulatory decisions, more than 30 regulatory submissions and more than 15 Phase III readout, all representing significant near-term activity. With this, also my heartfelt thanks to all R&D colleagues and indeed colleagues around the company for their dedicated effort this year as we continue being committed to improving people's lives.

Slide 25. With that, we will now open the call to your questions. As we always try to say, we would ask you to keep your questions to 1 or 2 each, it's Christmas, remember. You'll be notified when the line is open for your question. At that time, please make sure you only your microphone option 1 or option 2 to submit your question by clicking the Q&A function. With that, we move to the Q&A.

So the first question comes from Peter Verdult at BNP.

Just a couple and maybe the first one is not amenouon some minute detail or asset. But maybe given that it's 2 years since December -- the December ended when you were appointed, I mean there have been some successes and the less people -- there's been quite a few setbacks. But if you -- just to reflect on the last 2 years, where the biggest challenges are? And what you are from strengthening your R&D leadership team, any learnings and I think you're going to do differently going forward. That will be question number one. And then just more topical SPMS has been talked about as being a big area of high unmet need. So higher unmet need means -- it means to me that the risk benefit profile might be more skewed towards more tolerable. So how concerned should we be about the actual -- the ability of tolebrutinib in SPMS given the recent updates.

Thank you, as always for great questions. Number 1 is -- thank you for reminding me. Since we're in details, I think it was December 7, 2023 when we met in R&D Day. And at the time, I was pretty clear that I had 3 fairly immediate goals. One was to take as an excellent team at the time and make them better. And I hope that by looking at the profiles of both the existing team and those recruited, you will see that we've recruited a stellar team internationally recognized, highly experienced and innovative working together. So less than one was to surround myself with even better people. who are genuinely incredible and work as a team. And at some point, I hope that you'll see all of them. The second lesson was, of course, we knew we have failures and successes -- the key was to learn from these failures and successes I've said to you and more publicly that both Sanofi and the broader pharma community this year have learned that in areas where there is an existing standard of care Phase III trials have a different profile of patients that come in, and we have to be mindful of how we adjust our clinical trials both adaptively as they're in flight, but also mindful of what the existing standard of care is. And that's the lesson we've learned deeply and you'll hear as we go through questions. We've continued to adjust our clinical trials.

And then the third commentary is, while we have had mixed results, and we should be measured in the context of those mixed results, I don't want anyone going away from this call perceiving that, for example, amletelumab in any way was a negative result, a study that did everything we asked it its primary and secondary endpoints and provide patients with a q12 w dosing, we have a slew of data coming next year. And I think that if we get real replication those studies, we'll have a genuinely registrational or at least filable product with a major impact for patients.

And then to your second question, you made an excellent point about tolebrutinib. Just to be clear, firstly, the data on Tolle was super clear. when you look at CBP and disability, et cetera, into SPMS, the Kaplan-Meier curves diverged consistently and early. I think if you look at the data, really convincing you're right that we have to be extremely thoughtful about patient safety, we always are. And as we've gone forward with productive conversations with our regulatory colleagues of the FDA and elsewhere, we've taken the kind of direction that you pointed to, which is to ensure that we've got risk and benefit, including making liver function testing available to patients. Any more than that, said during an active regulatory review would be unwise.

Next question. So it's coming from Luisa Hector at Berenberg. Luisa?

I wonder whether we could touch a little bit on key learnings with tolebrutinib the Principia acquisition and that model and how things may have changed over the past couple of years, Houman. So I'm thinking Sanofi had a position in multiple sclerosis we have the BTK inhibitors, the safety issues came up during the course of development. So are there things you would do differently now in terms of ensuring that, that sort of early-stage knowledge that comes through acquisition is somehow retained and would allow you to maybe bring a next generation, which is superior when you do face some of these issues. So it's really around, I guess, investment into our early development and how you ensure with your next round of acquisitions and partnerships that you can keep all of that going so that you don't hit the stumbling blocks at the late stage and then I'm thinking Blueprint and some of the other deals that you've done, just how you might be approaching that differently -- and then since you showed the slide on your KPIs, nice uptick in patents for 2024, yes, but it seems to come from devices. What is that?

Luisa, thank you for your eagle guys. Without you, I think we'd be lost -- just to really move very quickly through your question. Number one is, I don't want anyone to walk away from this call thinking the Principia deal was a bad deal. As you heard on this call, Wayrilz has already been approved. It's an excellent product serving multiple patient needs. And I think there was quite a lot of smartness around different forms of BTK, the non-covalent with different residence times on molecules and also the ability to be blood-brain barrier penetrant. So what I don't want to do is in any way convey the view that, that was the wrong deal to do. And indeed, while some of those studies were negative. I think in retrospect, I wouldn't have sadly changed anything, honestly. I think it was an entirely reasonable thing to go across the multiple sclerosis waterfront, bearing in mind that even the modern McDonald's criteria so multiple sclerosis is a continuum. So I think that the criteria came out in the last 2 months. .

So number one is, I think we have to salute our colleagues for having been thoughtful and generated a real drug that's come to the benefit of patients and developed it in the appropriate -- your comment on -- what we can learn from these studies, -- number one, I think being thoughtful about early diligence as we do these studies is going to be important, of course, the diligence start is done here. we have an exemplary team who are highly experienced in diligence and BD to augment what was already amazing at Sanofi. But actually having scientific rig is going to be important. You said something very clever in your comment about taking learnings. Of course, this is the area of digital and AI. And without giving away any trade secrets, we have applied digital and AI to the BTKIs and have some thoughts about how you can modify their biology and their chemistry to maximize value.

And then on your KPIs, great question. As I say, thank you for your eagle eyes. We've got an excellent device group that sits beautifully between Brendan Callahan and myself, they've been incredibly productive, as you will know, in 2025 and 2026, there's an increasing value to devices they say they are heavily neglected area of drug development. And with the combination of RF, [indiscernible], the ability to figure out the temperature of medicines as they've given the ability to think about dosing schedules, compliance, et cetera, those devices generate huge amounts of value. So I think firstly, those patterns that you'll see are broad and wide relating to a number of device parts. I won't give on any trade secrets. But the first wave of those devices, as you can see, came from Sarclisa, which provided an on-body device that's excellent and is the source of real patient [indiscernible].

So the next question comes from Richard Vosser at JPMorgan.

Firstly, maybe a question on the amlatelimat readout. I think on the slide, it suggests first half '26 for all the data. Maybe you could just give us a if possible, a bit of direction on the cadence of events across the Coast 2 shore ACA and S3 trials, it suggests they're all in H1. Perhaps you could give us a little bit more color there. .

And then secondly, a question on vaccines. -- we've recently seen that the Sadara data or a deal for buying Sadara and the data from CD38, which showed pretty strong, I think, through prevention efficacy in Phase II. Just what's your thinking about this technology impact on flu vaccine strategy and how you're thinking about that within the development of future flu treatments on your side or vaccine.

Yes, Richard, let me take a otilimab and Jeff will take for the Sadara question, very happily. So just on AMLI, I'll be just saying you're right, the majority of the date, if not all of it will be available H1 or the border of H2, the cadence is pretty straightforward. At some early point-ish in H1, we will have the cost 2 and the SHORE study. those studies, as you remember, cost being a replicate of case 1, broadly speaking, sure being the combination of topical corticosteroids. We'll then subsequently have one that we don't talk a lot about, which is the hydro study, which is a combination vaccines and Aqua, which is the patients which are advanced biologic refractory. And then ultimately, as we walk through a [indiscernible] then very quickly move to Estey. It's a matter of great interest to me that we'll also have some open-label studies that will read out during that point, and we'll present throughout the throughout the medical conferences. So it's going to be very exciting. And then handing over to Jean-Francois [indiscernible].

Yes, thanks for the question. Of course, as you can imagine, we had a look at the [indiscernible] molecule, and we had some interesting discussion within the company. Basically, the data that they have generated are very supportive, as you mentioned. So certainly, efficacy reach levels that are compatible with vaccines. What we believe basically is that the SDRA molecule will be complementary to vaccine and not replacing vaccines and there are a couple of elements to believe that. And by the way, you probably noted that the Phase III is in a flu vaccinated population.

So again, another element supporting that it will be complementary. We believe it will be a complement to vaccination because we believe it's going to be mainly focusing on the people that have an extra need, have extra complication coming from flu infection, people that are immunosuppressed people with chronic kidney disease, et cetera. For sure, the molecule is not very convenient to be administered. As you noted, it's probably a 3 mL injection and probably 3 different injection 1 time, probably not something that can happen in the retail.

From a commercialization point of view, the commercialization channel needs to be built for sure, including reimbursement for that kind of molecule that can be given in the retail. The cost of goods for such a molecule, a molecule is doing a great job, but you need a significant dose driving the volume and the number of [indiscernible] you need to administer, but it also drives a cost of good. And the cost of goods that will be more specialty care product than vaccines. So when you put all of it together, we really believe that actually it will be a complement to vaccine and not a replacement. And I must say this is also what we heard from the SINA team in the past and Also, it seems to me that the ME team was also going in that direction when they position the product in line with the specialty care and oncology products. So again, complement and not a replacement at this stage, at least that's how we see it.

So the next question comes from Sachin Jain from Bank of America.

Two, if I may. So firstly on prexalamab, Homayoureferenced a couple of times taking learnings from the sole programs. I was wondering if you can just -- I don't know, flesh that out a little bit to how you're thinking about comparator trial design endpoints and where you are with the regulatory discussion of any changes you want to put through? And then the second question is on DP life cycle management. So Regeneron talked having, I think, some sort of follow-on candidate potentially less frequently dosed -- is there anything you're able to comment to today or when do you think we can get some updates there?

Sachin, great questions. You're right. We've taken learnings, particularly in RMS. As you know, our rates are now falling to 1 every 8 years. With that very low -- I'm sorry, background or it's fallen to every year. So powering to allow us to differentiate against time requires more patients. As you may appreciate, I'm not going to go into the details of exactly that, but we've had both thought about powering and interesting discussions with the regulator regarding exactly the SAP, the statistical plan. So yes, a, we've learned from the evolution of the studies that happened over the last 3 years during the life of the [indiscernible] study. And this is -- I was asked by Luisa, how do we adjust and learn. I think one of the things we've done is we've learned on the fly to adjust our trials to incipient conditions, and I think everyone will have to do that in the industry going forward.

Your second question was on, incredibly excited by our thoughtful partners and they're always incredibly insightful about [indiscernible] life cycle management staff. At this stage, I have no more to say, but I'm excited that George and in of [indiscernible].

So the next question is from Simon Baker at Rosebel. .

I may, please. Firstly, on tolebrutinib and going back really to yesterday, Human, absolutely get that for clarity and purity of application, it makes sense to leave PPMS and focus on nonrelapsing secondary. But based on the work done in the homes paper that you you lagged up yesterday. Once the dust settled on the main indication for tolebrutinib, do you think there's a way back for reappraising the potential for Tolly in primary progressive.

And then secondly, changing the subject a little bit. looking at immunology, one of your competitors sees mega blockbuster opportunities for cell therapy in the autoimmune immunology space. I kind to get what your perspectives are on the usefulness and potential of vessel therapy there.

Perfect. Yes. So Simon, thanks for the questions. I think that -- just to be super clear, and that home is paper, which I think was August 2025 in H Medicine, we sold be clear that the traditional -- what I took away is the simple traditional definitions of are going to change over the next few years. I think for the moment, the part from the least resistance in order to generate value for patients is in SPMS. But I think as the definitions, both McDonald's and otherwise. And indeed, the 35.0 code from the ICD-10 changes occur for reimbursement. I think we will all have to review.

End points and stratification for MS, including, of course, with MRI-based definition is that people went into. I think that's as much as I really want to say about tolebrutinib and then Thomas has reminded me very kindly about your comment on cell therapy. I think you've seen a veritable explosion of value in cell therapy in bispecifics that are T-cell engagers, as was myeloid cell engagers, but also an interesting emergence of in vivo reprogramming relevant to all of these disorders, both in oncology and immunology. You all know that while cell therapy is excellent as a proof of concept, and I think that various allo approaches may work in due course. They're not simple therapies to deliver. Our view is, as we said in December 23, in vivo reprogramming and our approach to bispecifics, where we're strong in large molecules and biologics is where we're focusing. But it's certainly a great proof of concept.

Okay. The next question comes from James Quigley at Goldman Sachs.

James? SP-3 I've got 2, please. Firstly, on itepekimab -- can you obviously speak was back in May or end of May that the trial has read out. So what are the potential options here -- is there any additional data that you're waiting for in order to make a final decision about whether to either start new trials or whether to stop the program altogether. So what are the potential outcomes? And what are the sort of options and data you're looking for?

And then secondly, on GP and CSU, could you compare the data package you have versus what Novartis has for remibrutinib, -- there's a lot of excitement about the remibrutinib drug out there amongst the investor community. So -- just wondering how you think about the data and how it compares and whether across your BTK portfolio, you could also look to potentially bring forward other assets, whether ibrutinib or another BTK in development into these immunology spaces as well.

Please James, your latter question was with JP and CSU. Just to be super clear, Yes, yes. The [indiscernible] I think it's not a helpful comparison to look through DPN comparing it to any other molecules there. Obviously, DPs spending 1.3 million patients here to use a complicated condition. Due clearly works and is safe and is actually growing beautifully commercially. And so while there's no direct comparison, I think up will continue to grow. And what's really exciting is the halo dupe developed in multiple inflammatory skin conditions and then moving into other organs.

And then your first question [indiscernible] and your comment is right about when the results came out. Remember, what we had to do is look around Blalock right, understand what other molecules we're doing in the space, which we have reflected on. We also had to reflect on what a replicate trial design would look like -- and then as you know, there's a bit of a delay between writing a briefing book and then having a conversation with the regulators to the most thoughtful path forward. That reflects the timing that's been taken. And I should say here that we've had, as always, a productive interaction with our alliance partner, Regeneron, will go to the regulator together and give you advice as soon as we have it.

So the next question comes from Sarita Kapila from Morgan Stanley.

Just a quick one one on the Alpha 1. Perhaps you could give us some insights into your early discussions with the regulator, how confident are you that you can file on Phase II biomarker data will you need to do an outcome study. And I suppose how much of an unmet need is they given recombinant for an early approval?

Thank you. It's a great question. Number one is, remember that most end of care needs to get to an 11 micromolar level, half the lower limit of normal for most of these therapies, both the Q3 and Q4W dosing substantially when above that and the Q3W dosing was really meaningful in terms of its concentration. So point one, the Dave is striking and clear point to is it's premature to provide any specific insights on the regulator. Suffice it to say that we've got very positive interactions with the regulator this very early stage after readout Phase II and we're figuring out path-forward. .

The next question comes from Graham Parry.

So just on M&A, you talked about augmenting the pipeline with M&A on top of replenishing internally, but just maybe help us understand how you see the balance between those 2? Is it 50-50, leaning more towards augmenting with M&A at the moment? And rationale for going into new areas. So I just see you've licensed to molecule in Alzheimer's. So are you starting to look to expand your therapeutic breadth. And then secondly, the regulators have lagged that in the U.S., they look at beef safety again. Just any comments on that would be useful at this point?

And then on Bravecamig, moving into later phase I, obviously, while the time you get to the market, therefore, there could be plus biologics and oral BTK in the market as well. So just help us understand differentiation positioning for that molecule in that setting.

Great. So I will take 1a/1b and 3 and hand to Jeff. So Graham, and I'm sorry, Pete has got out for a coffee, just like him. Pete, bring me coffee, please. I think the comment on M&A is pretty straightforward. In my 2.5 years here, I've been super clear that we'll be financially disciplined. But I regard my reflexes from where I came, are very clear that we're agnostic as to the source of molecules. We'll take the molecules wherever they come. We've got an incredible now disciplined research team under Mike Quigley, who both generate some molds internally is in a position to do excellent diligence and our skilled development team under Chris, et cetera, is incredible.

So honestly, we've got a really, really strong team molecules will come internally and externally, they're all experienced in that regard. But we also have additional tools at Sanofi Capital, which allows us to take stakes in companies as well as our Sanofi ventures activity. So punchline, we're agnostic as to the source of the molecules. We've got great teams that can pick the molecules up at any stage in that development or even earlier and move these molecules forward, and you'll see that our pipeline -- my key responsibility is pipeline replenishment and sustainability. We will always be good stewards of our shareholders and the company's capital.

On [indiscernible], there's been a whole securities history with towers that has been for beta. As you know, different forms of [indiscernible], which is in cellular rating the extracellular form phosphorylated in many ways and leading to different protein isoforms recently characterized by electron microscopy has been well established. And I think that the juries out or whether the tower is a great target. This is an opportunity for us to take thoughtful move into neurodegeneration. And the answer to your question, of course, is we are in neurology and it is one of our key areas. And you know we've done more than just this [indiscernible] did the [indiscernible] recently, too. I'll come back with the HS comment, but let me hand over to [indiscernible].

Yes. Thank you for the question. On the [indiscernible]. Of course, you may see it surprising to see the new requests coming from FDA. Given the confidence I've shown on the safety profile of this intervention, and I stay with what I was on this one. So very clearly, we have no signal that has emerged recently or in the clinical development. Yes, we have received additional requests from regulators. And so far, no surprises. -- requests [indiscernible] an update on the exposure. What we have seen the analysis we have done or it compares to background trend and there are no question that we cannot answer.

I just want to remind you that, yes, we are confident in the safety profile of the photos and the favorable benefit risk of the photos because we have done quite a bit of randomized controlled trial pre-licensure the [indiscernible] -- the Phase IIb, Phase III analysis showed the same rate of gas, for example, in placebo versus beforecipient. Since that time, we've done real dividends in more than 400,000 infants and again, no signals emerged. And so of course, we have conducted state-of-the-art pharmacovigilance. We have administered more than 10 million doses of defaulters in more than 40 countries and nothing to be seen from a safety point of view, nothing to be reported from a safety point of view. So again, it's normal that the regulator asked an update, especially when there is a change in FDA, but we have provided a confidence in the safety profile of that molecule no doubt.

Great. briefly on Bobenic. NHS remains a large unmet medical need to carry huge morbidity and some mortality actually. There are multiple stages of diseases. And actually, if you look at the [indiscernible] data published in JCI 4 or 5 years ago. It's clear that substantial heterogeneity not clinic, not only clinically, but also in terms of its molecular profile. I think there's very substantial space to make a difference. And Bravecamic, albeit early showed a very striking result both [indiscernible] 75. So you're right, it will be a slightly congested market, but biologic penetration is low and I think we have an opportunity to make a big impact on those diseases in the mono combination therapy. .

So we'll take maybe 5 more questions, and then we'll close the call. So the next question comes from [indiscernible] TD Cowen.

This is Chris on for Steve Scala. First question on vaccines. What are your latest thoughts on whether clinical efficacy trials are required to file new vaccines in the U.S., specifically a covi-lucombo with [indiscernible] and your pneumococcal vaccine with SK Bio. Second question is on IBD. You have several Phase II programs in UC and Crohn's. What specific unmet needs of mortgage segments? Are you looking to address it as you think about the target [indiscernible] profiles of these assets? .

Yes. So thanks for the question. As you mentioned, the policy environment is changing at the [indiscernible] in the United states. So certainly, we've engaged with the regulators on the different studies that we are conducting, I think, -- so power remain confident on Nemo and the fact that the design Phase III, so I didn't mention in detail, but actually, we've designed 6 Phase III, we had a productive [indiscernible] with FDA. And actually, we have enrolled multiple thousands of kids in these studies. So progressing extremely well. We had discussion on regulators. We had some minor adjustments to address the request, but we remain concerned in the pathway we have selected is the one that we will pursue for this one -- for the [indiscernible].

Then you came with a [indiscernible] combo. There -- you saw the data, I think they are very supportive. We have multiple options. [indiscernible] and the pathway might be different depending on the option that we put on the table. So this is a discussion that we're having with regulators and will be smarter in February when we have had the end of Phase II meeting with them. And then maybe you didn't ask for [indiscernible] for this one, clearly, we are committed from the get go efficacy having [indiscernible] control to demonstrate efficacy for both components. So there the question is not relevant for this one. That's why you probably did not included. .

And then very quickly on IBD, 3 comments on your TPP question. Number 1 is IBD remains a large unmet medical need even patients on standard of care either have an adequate response or a failed response only 30% of patients approximately 18 months still on their primary therapy. There are real opportunities left out there. And I should say, not just in common or garden IBD, but in fibrostonosin Crohn's in patients with advanced age with IBD, with young patients with IBD. And there's real opportunity to replace some of the existing and potentially relatively toxic drugs. .

We've started, obviously, our first move into IBD with Dupixent in EoE, which is often neglected, but is really important disorder, which DUPIXENT really works in. But also with [indiscernible], which I would argue is based on the current data, the best-in-class molecule, albeit at Phase II, we should see -- wait to see the results in Phase III. So the TPP we're looking for is different in multiple disease populations. And I think we'll end up working in multiple patients with IBD.

So the next question comes from Emmanuel Papadakis at Deutsche Bank.

Just a few follow-ups, if I may. So perhaps I'd like to add just timing. It's not on your 2027 list, which I was a little surprised about. So can you talk about timing of the readouts of both [indiscernible] Crohn's. [indiscernible], you said it's quite ambiguous commentary in terms of potential timing, but the slide says [indiscernible] So could you just clarify which one is -- like is that actually uncertain contingent on regulatory feedback? And then oral [indiscernible] sounds like you're still working through Phase III clinical development planning. Is it unequivocally going to be only combination studies? Or is there any scenario in which you take it forward as a monotherapy in [indiscernible] or dermatologic indications.

So thanks for the question. Efdoralprin definitely subject to regulatory discussions, which are going to be interesting. Duvaticorg goes beyond 2027. We've just engaged in the recruitment of the first patient into the Phase III literally, and we'll refine that as we go forward. And you'll be the first there, obviously, Emmanuel. And then thirdly, on [indiscernible]. We're just reflecting deeply on the data I think at this stage, it's premature to comment. I would say that the -- as we said in the last quarterly earnings, and we spoke a little the ACR 50 and 70 look pretty good, even though they weren't the primary endpoint were reflective of how we think about that going forward, normally in the decisions. And in combination therapy, there is certainly a position to combine it with various molecules, and we're working with partners to figure out how we go forward. That's not just an active discussion. It's subject to some biological work too.

Okay. And so we'll take our last question. It's Luisa Hector again from Berenberg. .

Thank you for letting me come on again. I'm still a little bit confused, Jean-Francois with the RSV like what the next steps are? Is it going to be both mRNA and the Vicebio and just any thoughts on whether you might need to compare it to [indiscernible], to pivotal trials and multiyear protection just how you're thinking about those as you move forward? And which of the options is the favorite at the moment?

Sure. So what we've shown today is that we have an RNA-based candidate, and we like the data that we have seen. We have reviewed them in the company, and we believe this data on the own are progressing this asset to the next stage, potentially to a large efficacy Phase III trial. In the meantime, we also like the Vicebio data, and we believe that there is a world where potentially customer want to choose between one and the other. So -- we like the data. You know is we also turned around a little bit the R&D organization in vaccines. We've accelerated the pace at which we generate data. And as we speak, while we like the data we have in RNA, we keep having additional data coming to us, additional data coming from Vicebio. So certainly, beginning of next year, we'll decide which assets we progress if we progress 1 or 2, and if it's only one, which is the 1 that we progress.

But basically, today, we have multiple options in front of us. I think we are poised to lead the field in R&D plus HMPV and the data you have seen so that we are competitive on both fronts. So more to come, and especially after a discussion with regulators as well on these programs.

With that, we'll close out the call. Thank you, Jean-Francois. Thank you, the whole IR team who've been incredible. I wish you a happy holidays, and I look forward to seeing you in January. We hope you've enjoyed spending an hour with us to review our scientific progress this year, and we look forward to keeping you updated as we enter 2026 with the pipeline just shared.

Before closing, I wish everyone a good upcoming festive period, and I look forward to connecting with all of you next year.

Thanks for joining us at the next session. I'm Graham Parry from Citi, and it's a pleasure to be able to introduce Sanofi and in particular, to introduce Paul Hudson, the CEO. It's great to have you here in Miami, Paul. I'm sure it's nothing to do with the sand and the sea that interest you here. It's purely been the investment community.

But perhaps if I can get you to kick off with some high-level sort of the opening remarks just to talk about where you think Sanofi is at the moment. And I guess the thing that's on a lot of investors' minds still is how Sanofi planning, the Dupixent LOE in 2031 and the sort of Sanofi look like post that date.

So a few things. We've come a long way. Just to give you some headlines. We were, I don't know, $33 billion in revenue when I joined around $45 billion now. We were 118,000 people in 2019. We're around about 72,000 now. We forget how many, but upwards of 70 sites in manufacturing, we're now 38. We've really tried to modernize the company, we exited consumer. We've tried to turn ourselves into an R&D led pharma company because we felt we were structurally going to be behind our peers.

We had to do a lot and invest a lot in our own pipeline and we even recommitted our buyers to that in '23 when we took quite a hit saying that we needed to do this. And we needed to do it partly because that's the future revenue generator of the industry, but also with Dupixent ahead of us, we have U.S. at 2031 and Europe at 2033. Some external watchers have us at around 2033 in the U.S.

We have a lot of patents. We have some good ideas that we haven't shared yet. We'll share those in time when we feel comfortable without giving too much away. But in essence, we have to get the medicines launched. And what I learned over the last years, we're a really good commercial organization. I mean we're really nailing it. We're growing close to double digit.

Dupixent, despite the threats and the wonderful people in this room that predicted our demise with lebrikizumab and everybody else coming, we grew 26% in Q3. This is the real deal. We know how to commercialize. And what that brought home to me over the last few years was we do need to get those drugs over line out of R&D. If we can get tolebrutinib approved, if we can get amlitelimab COAST 2 as a positive readout. If we can get lunsekimig into Phase III, we really know what to do. And it's been a bumpy ride. I should have perhaps signposted it more than it might be a bit bumpy. It's not my natural style.

But I'm really happy where we are right now. We have a lot to do, but I think I'm really happy with how we're set up with what we have plus the acquisition of Blueprint to come through the Dupi LOE. Should we underwrite that a bit? Should we add some things? Maybe that's part of the conversation? Probably. Yes, yes.

Okay. I was going to ask this. So when you look at your mix now between internal pipeline and M&A or BD, how do you see that going forward relative -- if you look at the strength of what you've got internally at the moment and the need to do additional deals perhaps to continue to fill out the pipeline?

Well, I think we -- if I look at the number of preclinical Phase I versus our peers, I think we're light. I think we're not where we need to be. We might be somewhere between 5 and 15 programs short -- high-quality programs, I think, short. We brought in our new Head of R&D a couple of years ago because he has reflexes in that area, perhaps even more so in the earlier space.

We're looking at a lot of things we'd like to add. I think we need to because if we turn the mid late-stage pipeline into what we expect, we'll have enough confidence to ride through Dupi grow EPS. But then the question will be, well, we're not so sure about your growth story, 33% to 40%. Well, actually, you can be more confident because these assets are now in Phase II, III as we get through the end of the decade.

And I think that work is also for those that follow us, which is making sure that we've spent all the time and effort becoming an R&D-led real pharma that we don't leave ourselves with a gap longer term. So we can do much more there.

On the sort of mid-late stage, if everything that we have -- not everything. Out of the 12 drugs that we have, if 4 or 5 are wins, we have enough to cover and to grow and to grow EPS. If we get 3 or 4 failures out of the next steps, then we're going to have to think more creatively about what we get from outside.

So you should see the emphasis in preclinical Phase I. You; should see as opportunistic in later stage. The Blueprint deal was really about underwriting the top line growth all the way through to the early 30s by saying, "Look, we're going to give you top decile performance on growth." As we turn the cards over and you get more confidence in the pipeline, you'll start to feel like now we're worth a re-rate. We waited a while, right? And it is what it is. But I like the way that's come together. The Blueprint deal was a little bit above what we were planning, but we were disciplined and I think to pick Ayvakit, which will be a blockbuster next year and then a little bit of pipeline behind it turned out to be a good deal.

Okay. And I guess the other thing that's been a focus of investors is margin progression. You're a bit clearer on Q3 about how you see '26 panning out. But I think the '27 commentary is a little bit more cautious, and this is -- the extent to which -- if you can just clarify the extent to which that's just around the Regeneron R&D offset going away?

Yes. Look, it's been a big deal, and it's in the high hundreds of millions. Of course, the AMVUTTRA royalty is coming up fast. And while they're not like-for-like, the gap will close. I don't want you to have a consensus for AMVUTTRA in '27, but it's a big number. And we're looking at 30% of that. So I think we feel quite well placed for bridging that.

Plus we move towards a more specialty care-led portfolio, which has a mix benefit. We're becoming more efficient in general as a business. And you should look back -- if you look at Q3, we were 8.8% growth on the top line. We were 9.7% growth in BOI. We were 12.4% growth in EPS and minus the buyback 10.2%. We like the shape of that. I'm not saying the numbers will be the same when we guide for '26. We won't guide for '27.

But you should see us driving numbers that show our efficiency and our ability to execute and show an attractive P&L at the same time as growing the top line and investing in R&D. That's the job, right? But I feel we -- in Q2, we were not clear enough about our desire to run a leveraged P&L. And we went to great length at Q3 to make sure that there was no misunderstanding. The company where we're at still with a sort of could do better in R&D, then we must deliver the financials.

And as is the case, not everything hit through the course of the year. So to what extent was the ability to grow BOI next year -- margin next year down to perhaps a lowered R&D budget? Or does the R&D commitment stay there and you just refunnel it into earlier-stage projects, if you're not running quite as many Phase III?

Well, I think some stuff graduates. Some of the OCEANA, the amlitelimab program graduates. So it leaves us a bit of capacity. I know people would love to say, "Well, if nothing hits, we will redirect the resources. Things not hitting is more of an issue than the R&D spend. And that would force us out to try to buy things that would come with R&D spend most likely. I think we are in the sort of 8 and change region for R&D.

And I think that we should try and manage within that. And should we do something opportunistic, maybe add a little bit. But I don't think we should get ahead of ourselves. For a decade plus, we were around EUR 5 billion. It was never going to be enough to replenish what we had ever and we made the tough decision to add more and take the hit back in '23. We shouldn't blink now, particularly as we have an approval ahead of us, the second Phase III pivotal on amli lunsekimig phase II.

I think we have enough going on to say, "Just stick with us, we'll do that." The Phase Is, we can add them. We can add them a little bit later in the year, even we don't have to see a big rise in R&D spend. We've kept G&A roughly flat the entire time I've been in the company. And where we pushed the sales piece, we've had it back in top line growth.

So I think we're doing things right. The question is, is the total R&D investment getting the return and I think there's still a question mark. When I look at some of the bumpiness of this year, it's often attributed in sentiment-wise to just can Sanofi really just get out of their own way and do some R&D. But we had a standout win on itepekimab Study 1 and Study 2 or fail.

Roche had 2 underwhelming study reads out, AZ failed a Phase II, and we'll go to Phase III, in my opinion, without a recognized subpopulation. And so we're all finding some of these things quite difficult. It's not just us. We've chosen a difficult area, but we've chosen an area that's high reward as well because we know this, and I've spent some time, some of you in the room have heard me mention this today already.

There is something special about immunology. While it may be harder and there may be some risk when you do get approved, a company like ours that can execute you have a multibillion-dollar drug literally by just being not the other things. That's the function of highly heterogenous, highly symptomatic patients that are never happy with their treatment. And so getting approved and then putting in our commercial hands is really the meat and potatoes now for us.

Got it. And then the other sweetener, I guess, on the margin has been the capital gains. So you've done about EUR 0.5 billion a year. That's been pretty consistent. I'm not quite sure where you find all the products from. So how long can you keep finding products?

Well, I think the history of this company, there's no short supply of products. One of the interesting things when I joined in '19, I went around the world, and everybody that presented to me had a different portfolio. So we've managed -- one of the reasons we dropped the number of sites, we were, I think, 300,000, 400,000 SKUs.

I think we're around about 200,000 now. All of these are the efficiency gains. We will make around about EUR 0.5 billion in capital gains. We'll drop about EUR 200 million in revenue that we'll have to make up for those divestments. But that's good business, good pruning. And I should have said this earlier and I didn't when you asked about R&D spend, but the -- we're also pruning some of the R&D.

So what you don't see is a little bonsai work that's going on where perhaps we were trying to get beyond indication 1 and 2 with some of the immunology drugs because you can. And I think we've sat back and reflected and say, while we could go after some smaller indications, 80% to 90% of the value was on indication, indication 1 and 2. So why don't we just do that and remove the opportunity costs on doing the other indications that may have washed their pace, but that money is better for us deployed elsewhere in R&D. You don't feel that pruning, but that's going on regularly.

Got it. And just moving to the pipeline, you touched on a few of the things. There's been -- as you say, there's been a few -- some hit some misses. I go back to the R&D Day 2023, there's a sort of basket of products you put in the EUR 2 million to EUR 5 billion peak sales range and then some at EUR 5 billion plus. So if you assess your scorecard on that, how happy are you with where you've got to today? And would you reorder those 2 to 5 and 5 pluses?

It's probably better you tell me because we -- if I look at where we are, where we could be with the next steps, I have amlitelimab squarely in the 5-plus. And I'm actually more confident now than I've ever been. Again, when we released the phase I data, we crushed primary and secondary endpoints. The market, I think, was a bit underwhelmed because of the effect size comparison to Dupixent because everybody sees it as a DECT comparator. Dupixent grows until its end. Stop worrying about that. We have a plan for that.

The question is, can amli -- amlitelimab be EUR 5 billion on its own? Does it stand on its own? Think of it as sitting in another company. We were blown away by the fact we could start patients and have success on a Q12 regime. It's the same group of people that asked me, "Paul, are you interested in this company with a long-acting IL-13?" And I'd say, "Not really."

And then I'd say, "Well, I have a long-acting OX40-Ligand." It's almost like the same person can't think about the same thing twice. And we -- if we're really Q12, you know how it will work for biologic naive, the physician will tell people for the first time, you're going to have to go on an injectable treatment. The patient will say, how often?

The physician will say, every 2 weeks, maybe every 4 weeks or there's 1 every 12 weeks. They won't even ask what it is. And we love Dupi, Dupi grows. A group of patients just don't want to do it, and we'd rather do a Q2. That is a major percentage of naive.

With amli on top, there's a chance of drug-free, disease-free remission for a small population, but the promise of it at initiation is enough to inspire people that amli is certainly worth 1/3 of new patient's initiation. That's why we go beyond 5%. There'll be a debate about how quickly the efficacy is onset. So I think we should not try and appear as the first choice for a patient that is what I call the hot patient who comes in highly symptomatic and need something quickly. I think for the 91%, we should be looking at taking a 1/3. So I'm very happy with the number.

Yes. Okay. And you said, as you pointed out, the effect size numerically when you compared it to Dupixent was low, and it actually looked more like the Amgen rocatinlimab data, both of which had looked for higher effect size in Phase II. So just talk us through what your thoughts are on why you saw a drop off in or a numerical -- numerically lower effect size in Phase III versus Phase II?

Well, I think I mean just take one step back. Look at the consensus for the other drugs, we could pick NEMLUVIO for a moment. We know that up to 50% of the patients drop out at 6 months because their idea is no better. Consensus is around EUR 3 billion. The effect size is lower than every drug you mentioned.

So let's take it on both levels. What are we really talking about? We're talking about new mechanisms with long interval with an increasing efficacy because we were only 24 weeks in that study. So we feel very good about the class. We feel very good about the ligand. It's not really an issue.

I think what has materialized and you've seen it with some drugs, IL-17s that have surprisingly failed or IL-5s that have failed in certain diseases. Where you choose to do your study and who you choose to include is more important than it's ever been. When Dupi was first out of the blocks and everybody was naive, the effect size is massive, everybody is excited. It's a miracle. I've been there before when we launched REMICADE 1,000 years ago. If you were to do the Dupi studies now, I think as amazing as this medicine is, you may find it middle of the pack, not because it deserves to be, but the patient selection is getting more demanding.

And I think we're going to find, by the way, a more complex set of results from biologics in autoimmune disease over the next half decade until people iron that out. Many drugs are already in flight. So it's getting very specific and very important to know your biologic experience versus naive in your sights and not just look at the total and make sure the screening is perfect.

So I don't worry about that. I know that if you can give somebody incredible benefit over a 12 weekly regime with an efficacy that keeps improving with a chance of remission, you are a major player in atopic dermatitis. That's all I really care about. Again, we know how to commercialize things. That's not really the issue. That profile, but I spoke to our commercial leaders after COAST 1, they're like, "Can we go now?" That's -- they know what they have. And so we should really wait until we're approved.

So we'll get COAST 2, and then we'll deal with it after that. But that's the sentiment because we know while you guys like your cross-trial comparisons, we like the fact that patients who need a great medicine with the right profile will get it and we'll go fight there.

I think in the past, you've alluded to or talked about the fact that in immunology patients cycle through therapy for looking at psoriasis, multi-class drove a lot of penetration, et cetera. Do you think that is how, ultimately, the AD class will? So therefore, do you see that if the Aquis results are positive in the Dupi experience patients, that, that is also a sizable part of the EUR 5 billion that you talked about?

I think Dupi is going to grow to the end. We gave some ideas around EUR 22 billion, I think it was in 2030. People last when we gave EUR 10 billion in 2019, nobody is really laughing at the EUR 22 billion. So Dupi is so well understood and so many indications and so trusted this profile is without question. I think what's going to happen is there's going to be an absolute mirror replay of psoriasis. And I find it a bit surprising sometimes that people haven't sat back and said, "How can 4 IL-17s be successful in psoriasis and HS? And how many advanced therapies are there? 10, is it all blockbusters? One oral is not going to get to blockbuster status, but everything else that's injectable is a blockbuster.

And when we look at head-to-heads and we do effect size comparisons, don't forget that most patients, and I think you touched on this, will have 2 to 3 or more biologics in their life with the disease. Everybody is moving all of the time. These patients whose lives were horribly impacted, they go on a great medicine. They get 95% clear and they're pissed about the last 5%. And a few years later, they say, "I need something else." It's normal. Expectations get raised. We've seen it play out carbon copy in psoriasis. And in '23, when we did the R&D Day, we used psoriasis as the example. We said you go from the first drugs, which are not normally as good as Dupi, but come in like a HUMIRA or REMICADE or Enbrel, in fact, then you become more selective and more efficacious.

Well, Dupi sets some of that bar, but there's still room. And then you go to interval and then you go to oral. And all of these things take the patient pool. And we know -- we absolutely know for sure that the reason Dupi grew 26% in Q3 despite 2 or 3 new entrants is because biologic penetration is less than 15%. So 85% of the patients that should be on Dupixent are not on Dupixent, which means that every time there's a new entrant, all boats rise, and we're the market leader. It's going to be the same, exactly the same. That's why I find it a bit perplexing when people don't study psoriasis and say, "Let's apply that to AD. Hey, and let's apply that a bit to asthma, slightly higher penetration. But what happens if it plays out the same? It's going to play out the same.

Yes, yes. In the AQUA Study, I think the patients enrolling are allowed to have failed a biologic or a JAK. But in the treatment paradigm, JAKs tend to get used later unless they're sort of used for an immediate flare resolution in the short term at the beginning. So in that study, will you be able to tease out the patients who have Dupi or biologic failure rather than from the JAK failure patients to get a clearly defined population?

Yes. But the goal of the OCEANA program was do we believe this drug can be one of the winners to go beyond EUR 5 billion in asthma, of course, but importantly, in AD. When we put the program together, we tried to understand what the physicians might want to see. It was less about competing with JAKs or Dupi. It was more about saying, "Can you recapture a significant efficacy response in patients pretreated with advanced therapy?" It's more that.

It's more on top of topical corticosteroids in AQUA. It's more saying, in your practice, in your office, who you're seeing? Can you have confidence to initiate for naive? Can you have confidence efficacy -- so post? Do you have confidence that efficacy will continue and mature SGRE? Can you go on top of other things, AQUA or responders? Sure, rather, for TCS. So that the position builds extreme confidence in being able to say, I see the utility at first advanced therapy or later, it's worth us trying. We just wanted to put the full data set together, so get close to and move from there.

And if I sort of understand it correctly, the way you talked about it initially, you talked about the frontline naive market, the first and potential for remission. So if you think about that 5 plus for you, is that more weighted into the naive patients than it is into the post DP3?

I would -- I know I read some of the notes and things and the sort of overly simplified view sometimes of those that watch us is, well, if you're not as good, you've used afterwards. It's really the opposite. The question is, what are the things that drive penetration? It will be interval in that case, chance of remission.

And so if offered to naive patients, that's a huge amount of naive patients. So if that -- in that context for me, and I have the numbers close to hand, that would be 1/2 to 2/3 of the patients. And of course, just because you're not an IL-13 means you get used later. You just get us later. Again, if you're an IL-31 and one of the comments on the label is may make AD worse. The real thing is you're 31, you're not a 13. And I think that's what gets physicians excited to try a different mechanistic approach. I have to say, I agree with that. I think that's the right thing. So we'll get a lot later, but we'll get more naives than people realize.

Most likely again, needle burden and for many who don't want to ever do that themselves 4 times a year is actually, you know what, I may just get it done in the office. That's a tiny bit easier for everybody. And you don't have to meet a certainty. So maybe I'll do my class and then go the following week. That level of flexibility is pretty extraordinary. So I think we will get a lot more naive than people realize.

And I might switch to one of the other assets that's more imminent, I guess, as well even tolebrutinib. So you have the PDUFA date coming 28th of December, which is delayed. Perhaps to the extent you can talk about sort of what label you're aiming for or hoping for from the -- in the non-relapsing secondary progressive setting?

Well, what we had in the study was no relapses in the last 2 years and still progressing. That's 25% to 30% of the MS patients. I'm okay with that. If we get PERSEUS data that gives us a SNF at the primary progressive, could be another 5%, 10% of the population. Overall, that's a big population for us to go for, more than enough to make it a multibillion-dollar drug back to the -- can it be 5? Can it be more?

I think the reality for us is we would just like to get approved. We used the voucher. We got earlier review, and then we lost the early because of the FDA taking more time. I don't regret on that unmet need, not a well-understood part of the disease because there's never been any drugs.

Also incumbent upon us to make sure the REMS is perfect. I said it to a few people today and yesterday, but said it to the team, launch uptake is not my concern. REMS uptake is my concern. Perfect REMS Perfect, perfect, perfect. So that if that means you take longer to have an end-to-end, nurse visits your home, blood draw, physician sent labs, physician confirms receipt of labs, physician confirms reading, it's like getting your -- whatever it's called, do you confirm your reservation for dinner and everybody is scrambling to -- that is what -- how we want people to feel because if you're doing weekly for 90 days and the physician gets the labs and acknowledges reading them, if they're elevated, you stop them. And if they're not elevated, you continue. It's that simple. It's that simple. There's no burden. But if you mess that up, you get a halo you don't need, it stays around. And given that it's unlikely we'll have a competitor for 5, 6, 7 years at best, no need to rush that. No need to rush that. We have modest expectations for '26, and we have more demanding expectations thereafter.

Yes. And just going back to the label. So do you -- I guess the question is that the FDA ahs never actually approved non-relapsing progressive MS drug with that label or definition. And it feels like the McDonald criteria is shifting. So is that a definition that you're discussing...

Are you coming back to active versus nonactive?

No, no, just more about is it going to be an MS label defined population or wording of non-relapsing secondary progressive because the physicians all recognize what that is, but FDA has never recognized that. So...

Yes. Well, that's right in front of us. That's I mean, literally right in front of us now because I think that's part of the challenge you go on, sometimes with the regulator, you -- everybody agrees with the study, everybody agrees you're trying to treat. You do all the work. And then when it gets to it, like and say, right now, you -- and there's a little bit, I think because of the elevated liver, I think there was a little bit of, let's try and be really sensible about who's defined.

Our position stays firmly. It's those that we studied. There is no point trying to recharacterize. Should, by the way, the MS definitions change completely. You know this, but the entire specialty says it's phases of disease. It's not different diseases. So everybody is progressing some more than others and some are having relapsed some more than others and it may change on their journey. So let's address -- it's funny enough. It's one of the reasons why frexalimab will be in the top club because of its impact on innate and acquired immunity, It may be the one medicine that actually is stand out like best-in-class on efficacy and relapsing, but actually addressing disease progression at the same time.

We thought for a while should we do CD40 ligand frexa and tolebrutinib, should we do combo. And I think we're going to find out does the data emerge with frexalimab that it addresses progression enough for it to be the one and done. That's going to get interesting too, but the definitions are completely out of touch with reality.

So what do we care about making sure that the population that will benefit is the population in the label and that we're not constrained for reasons that make no sense.

And the delay happened just after the GEMINI data on disability progression were presented. So is that the -- what was filed with FDA that led to the delay and the major amendment? Was it specifically the disability progression data from the relapsing studies?

Yes, the -- as we said, and they know the GEMINI population is not the secondary progressive population, HERCULES. So you don't learn a lot. I think they wanted to see all the data. Remember, we have over 4,300 patient years on tolebrutinib and I think it's okay to ask for more data. If we were in a race to launch with somebody else, I'd be irritated, but the truth is we're not.

So I'd like everything to be done. It's painful for me much easier to get approved. People take that overhang off. We move the short term has disappeared and everything is happy. But in reality, a great label, perfect rems are the only things that I care about because that's long-term value creator. So we will see.

A question I've been asked quite a bit since I've been here, in fact, is, well, will they ask to see the PERSEUS data? And if the PERSEUS data is great, I hope so. But there is a chance, and there's no indicator for this. But if the PERSEUS data comes while we're still talking about the label, what if they ask. And the answer is I don't know, and I've been telling people for the last few days, I really don't know. I worry less if it's great data than I do if it's not. But I think if there's been an extreme safety signal, we would know about it already. So maybe it's just more data. As it happens, we say we look forward to the PDUFA on December 28. We've given them everything that they could possibly want and we take it from there.

Got it. Fast forward to December 30, if you assume you've got an approval with nonrelapsing SPMS, how easy a population, identified or population do you think that is for treated patients because who are already sitting on an anti-CD20, but haven't had a relapse for 3, 4 years?

Well, it's easier than we would have imagined. It's -- they're not identified, but they're known. And what do we mean by that? And many neuroscientists at Mount Sinai not that long ago, where they're explaining to me, they know exactly who the patient is. But right now, they're not recorded as non-relapsing secondary progressive MS because if they are, their insurance company won't pay for OCREVUS if they give them a definition that's not covered by the label, therefore, the insurance. So they leave them on the old definition because they don't want to take their OCREVUS away. I think that's fair.

While there may be no data to support it, and this is just anecdotal what we hear. I think it's quite important that the patient feels they're doing something, right? And OCREVUS is an excellent medicine. So I think what -- they're not identified, but they're known. And if we're going to go slow and perfect on REMS, every has plenty of time to know who it will be. I can tell you since the delay and the PDUFA, the number of e-mails and letters I've had from patients saying, "Hey, you are going to get this done, aren't you?" I'm like, "I got enough pressure from investors. I don't need real pressure, but we joined the industry to do that, and that's what we're doing.

And aside from that, do you think there's a community of patients or a pool of patients who just dropped off therapy? Or are they new patients on some...

There may be. We've done a lot of research. It's hard to tell because I think if you're a secondary progressive patients and you're using a cane. And I'm oversimplifying, but the journey is towards a wheelchair. And the data doesn't support it, but you feel like it might help, you don't really drop off. There will be some, particularly in the constrained markets in Europe where they never use advanced therapies at that stage January. But by and large, in America, I think it's not the case.

Yes. Okay. move shift gears on to itepekimab. So one hit, one miss. Maybe just run through the differences that might account for the differential results and then what your sort of steps forward from here will be?

Well, that was is because that sort of was our run into that part of the year where a home run would have been nice, get coast 1, get coast 2. And it's hard for me to be press with the team because they did 2 studies perfectly. They just got different outcomes. That's the business we're in. I did tell you earlier suggest that it's getting harder to take for granted studies in immunology.

You've got to be much more real time. AERIFY-2, we believe, not 100% of the reason. So I won't -- I'll deny it, if you say I said that. But one of the leading reasons for AERIFY-2 was the legacy of COVID restrictions. So remember, with COPD patients, we struggle a little bit, they struggle with infections that lead to exacerbations that lead to problems -- and that's the background expectation.

And that was demised because many patients would have got an infection didn't go out or war a mask. So we made it harder to get a delta -- and it looked like people are doing much better on control than you ever imagine. Well, they weren't. They were just taking these incredible precautions.

So we needed to have that sort of bias to understand. I said that we shouldn't really do another Phase III. If we're not sure that -- if we have the same probability of success we had with the other 2, we feel confident that a major contributor to say like that is COVID and that we can do something about that now. Again, don't forget, Roche struggled with both studies. AZ failed the Phase II at least from recollection.

So what that means is, whereas I would have hesitated if we were falling behind in order of entry. My real clock is ticking is kind of get to market with itepekimab before I lose leverage of Dupixent rebate with payers. If I can get there before the end of the decade. And if IPD are right and we're through 2033, then I have 3, 4 years to deploy rebate to make us the preferred 33. People say, what about PBM reform, 25 years and waiting. We may have a shot of making itepekimab the outright winner in the 33s. If we leave it too late, more complicated. And so that's still the plan.

So AstraZeneca has got Phase III data on tozorakimab coming next year. Their studies were post COVID. So if you're right and it's COVID, they may not have that inhibition could be in the market earlier. So is there a risk they just still particularly the lower eosinophil segment, which is kind of the obvious...

It's very possible. It's very possible. And look, we'll take lunsekimig into COPD. Look, we're back to what we said about psoriasis. People should not get hooked on winners and losers. They should get hooked on biologic eligibles and penetration. That's where you go to know if all boats will rise. I think it's better to have more mechanisms for patients. We take a 13 TSLP and we can get a high T2s, who knows. I wish everybody want them all to do well because these patients are struggling.

Again, they could be before us. I think one word of caution, I don't remember, you'll remember the study better than I do that the -- I think there are old comers. And we saw Roche do the same. We focus on former smokers. We think the delta is bigger there. And so we will see how that plays out.

Got it. Okay. And just as you mentioned the lunsekimig, what was the rationale for taking lunsekimig into a Phase III COPD before you've seen the Phase II asthma? Do you just feel that it's totally unrelated and there's a mechanistic rationale in COPD to go straight to Phase III?

Yes. Look, they're different diseases. And there's -- I wish I could tell you there's a good reason to wait. I want it to work in both. Well, the question we have to ask is, would we stop the COPD work if we fail in asthma? And the answer is no. So why wait? And we know IL-13 and TSLP work extraordinarily well. We know IL-13 works well in AD, but not so well in asthma.

We know TSLP works very on asthma, but not so well in AD. But we know it may work not so well, but there is a 1 plus 1 equals 3. In May '23 in D.C. at ATS, we saw a Pheno drop of 1 plus 1 equals 3. And so our bet is for the high inflammatory burden COPD patient, if you're going to get efficacy, it will work. And same in asthma. Our hope is that lunsekimig is the standard of care where efficacy is the lead consideration in asthma, we'll find out.

I'm just checking if there's any other questions. I might just throw one in on you're taking on the pharma chair. What's top of mind in the agenda as you go into that role?

Well, I would just -- as I pivot into that, I would say what we've been able to talk about is duvakitug, which I think is going to turn out to be one of the best deals I ever did, the TL1A with Teva. I think it was smart for them with us. I think it's smart for us. The data is telling us we may have best-in-class. We'll find out.

We're already in the Phase III with UC. And I would put that up there with the big medicines now because it could be. The other one, just to point it out because of the continued -- the philosophy of markets growing, Brivekimig, the TNF OX40 in HS will be -- we think it will be a 2 product race eventually, which puts us at a multibillion-dollar drug. And so don't -- again, everybody is looking at winners and losers. Do not think winners. The only thing winners and losers if you're 80% biologic penetrated. If you're 18% or less or whatever, everybody wins is degrees of win. Everybody is an EUR 2 billion-plus drug, everybody, summer 5. That's where the differentiation and the commercial execution makes the ultimate difference.

As for the Pharma Chair, you get on the journey to that 5 years earlier. You run through each committee, and you just assume you'll get there at some point. It's a big responsibility and honor, of course, and I represent Europe at a time when that may be more important than people think in the room in terms of medicines. 54% of medicines approved in Europe are not available to patients in Europe through reimbursement. I spoke to [indiscernible] his team, President Macron. And there's some sensitivity, the fact that with MFN that medicines may not get approved in Europe because they'll be at U.S. prices.

Well, they'll get approved, they won't be reimbursed. And they look at me like, this is tough. I said, before Trump, 54% of medicines are not getting reimbursed. So that you've got some work to do long before that. And so it can only get worse. I feel some responsibility for that. I didn't join the industry to drive further health and equity. So I don't like that. I would like to try and bring the President wrote to 17 CEOs.

He did not write to Pharma. I'd like to get pharma back to be the convener. I'll try and play my part in that. I'd like to turn some attention to PBMs as tough as it is. And I would like to try and get a much more active debate on the fraud of 340B and duplicate discounting.

So if I can do some things that capture the President's imagination that are good for patients and good for us, I would like to stand for that. You had 2 halves as Pharma Chair, your own company. And Albert showed sometimes you have to make the company core. I respect him for that. I hope to continue to wear 2 hats through my tenure and do something good with it.

Fantastic. We're up against time. So that's very interesting as always. Thanks, Paul. Great interview.

Thank you.

Thanks, everybody, for listening in. Thank you.

Thank you. Thank you.

Thank you guys for being here. Pleasure to have the CEO of Sanofi, but even more importantly, Chairman-elect of the PhRMA organization, which I hear is not the most effective organization in the world. So which one are you more excited about? Let's start there.

Well, I'm very excited to be the CEO of Sanofi, of course, and we have some readouts ahead of us will tell me whether my excitement is well placed or not. On PhRMA, I was one of 17 CEOs who got a letter from the President in July asking us to voluntarily adjust our prices worldwide in favor of the United States. And just as a small side bar, you don't often get a letter from the President of the United States. So -- addressed to you personally. So I sent it to my kids in the WhatsApp group. I said, oh, I had a letter from the President of the United States. And they go, way to go, dad, you're the coolest. I went, none of you read the letter.

Then I go, Dad's going to jail, Dad's in trouble. And I think Trump -- whether you like the chaos, whether you understand the chaos is orchestrated, to push us voluntarily to make a call on what we do rather than legislate, which may not get through in his tenure. Whether you like it or not, it's having an effect. 5 companies has gone already. For me, as the incoming Chair, the first order -- the first thing to be concerned about is the disintermediated PhRMA and went to the 17 companies.

And so what is the role for PhRMA as intermediary and mobilizer and convener in that situation. I think I hope to reset a bit of that. I think you once said on a podcast, my personality is perhaps more akin to being in rapport with the President.

Donald Trump's golf buddy.

I'm not sure I felt about you putting us together so closely. But I do know that, I think it's my job to say we can bring the industry together, we can do better things. That's, first of all, confirm that this is the end of what you might be trying to do in your tenure, if possible, I don't know.

Secondly, okay, what about the PBMs and 340B. There's going to be some things carved out. There's going to be some demo projects, all the rest of it, but duplicate discounting, one, the PBMs, once again, managed to stay out of the fray. And I think if you've taken a win voluntarily off us, we're next for your voluntary win. And so I'd like to broaden the field of play, if we can, and shown them that we can get a few people to be involved.

As it stands, he'll take some wins. Some companies have gone already. We'll see what happens next. And we don't know, by the way, what happens if you stay out and don't agree. And I'm sure many companies are watchfully waiting to see what is the tipping point for them to be involved. I don't know. I can't comment on others. I know we have been having a dialogue with the administration since before the letter, and that's continued throughout the process. So we'll see and do what's right for the company at the right moment. But as incoming Chair, I'd rather not be disintermediated, then I'd rather try and bring everybody together, then I'd rather try and direct the fire towards something good for patients, good for us.

Got it. Paul, I feel -- and I genuinely meant it when I said it on the podcast a few weeks ago, I feel like some of the PhRMA CEOs, at least from a personality perspective, this administration, more than any prior administration seems to be very focused on interpersonal relationships and sort of really a more expansive set of relationships.

I don't know if that's truly been pursued by many of the CEOs. And I'm curious, where are you with that process? Is that a high priority for you just at an individual level to spend that time to actually convey some of these priorities?

Look, I'm -- you don't -- you go in sequence to become the Chair of PhRMA and you work yourself through the committees. And you make a bit of an effort because you think at some point, you're going to try and do something important for the industry. When I started a few years ago on this journey, I didn't realize we've been in quite this moment. And I think it's important to have some very direct conversations that are perhaps slightly less policy-driven and slightly more headline driven.

And we know how it works. We know how the President has got everybody to the table. We know that these are the things we said we would never discuss. And here we are, and some companies have gone already giving up ground. I just think that we need to be realistic. The President is looking for wins. The midterms are ahead of us. It's not pretty at the moment. Popularity down, we're in the 30s, I can't remember. So it's a struggle. And I just think there are wins on behalf of the American people out of pocket, all these things that could be addressed, should be addressed, but there'll be good headlines.

I don't come in until January. I think Albert is a big personality. And Albert has done what he can to try and manage this process. But of course, he's also had to make the best decision for Pfizer. And he's clearly made that decision. I'm not speaking off the record with that. But for me, I think I have a similar sense of smell for big wins, and I would like to try and bring that. I don't know whether the President will think I'm his cup of tea or not, but I will -- and my golf is sufficiently s*** to make sure that that's not an issue. So we'll play it by it.

He'll win, he'll win. I guess -- so which -- where that leaves me with is, clearly, a settlement with the administration is a top priority for Sanofi, I would imagine. But also being an inbound chair of the PhRMA organization as well, how do you balance those 2 in terms of preserving that PhRMA is not disintermediated, but technically, you did get a letter individually and the current chair already did their own settlement. So how do you balance those 3 things?

Well, I think PhRMA has shown that it has to evolve a little bit because Albert still chairs PhRMA and has already negotiated his own deal. So you can be on both sides of that conversation. I know that PhRMA is really about policy, right? We don't -- we have -- the lawyers sit in the meeting to make sure it stays about policy. And I think policy what's driven it for a very long time.

And I think the policy conversation has never really changed whether people did deals or not. For me, you take on the chair to try and do the right thing for PhRMA, but I have to wear 2 hats. And in the end, the company agenda has to be the priority for me. It's what I'm paid for. But I don't think that those goals are mutually exclusive. So I give myself a good shot.

But you will parallel track both of those. Is that fair?

Well, it depends what you mean by parallel tracking. If you say, am I waiting around the corner from an announcement, I'm not going to share that with you as nice as you are. But I told you, we've been in conversation with the administration since before the letter. That never changed, and that will stay that way. I've got and we have a very good relationship with the administration. I've spent plenty of time on the hill and with the key decision-makers.

I'll do what's right for the company. I'm not the incoming Chair. I'm not the Chair until the end of January. So much is going to happen between now and then for everybody. And then we do what's right for the industry in the long term. I didn't take the job -- any job in health care to drive more health and equity, but that may be where we're going certainly with Europe.

Makes sense. As it relates to...

I'm sorry, I should say, this maybe appear controversial. I don't mean it in this way, but I've had the opportunity to meet 3 heads of state in Europe over the past weeks. And I've asked them how they feel about the United States setting prices for their medicines in their country. And they all say, to greater to a lesser extent, it's outrageous or it's complicated or it's not what we'd like, different answers.

But I said, well, here's the interesting thing. 54% of medicines approved in Europe are already not available in Europe, not reimbursed. So that negative battle on your desire or not to reimburse innovation in Europe exists pre-Trump. It's pre-Trump. So you don't want to reimburse the drugs, 54% of new innovation approved by EMA. You've already been on that journey. So it's a nice wake-up call. And again, whether I like the present, don't like the present, like the value, it doesn't matter. What's interesting for the first time in my executive career is European heads of state recognizing they have an issue with this, and they have to do something about it, and they have to pay for innovation.

Do you think they can find it in the budget dollars?

I think most of them have no money at all. And so the question is, do you keep the same budget move prices up and just give less people medicine, zero-sum game? Or do you actually try and free up some money knowing that it may spark inward investment in your country. There's always -- in Europe, it's always had a disproportionate level of inward investment for what it spends on medicines. That is how it is.

And I think that's very reasonable for them to think that. But so that means if you're Germany, the U.K., we all love Oxford, Cambridge, Imperial, UCL, but it's not enough if none of the medicines are available in the U.K. We may invest in early science, but we shouldn't build manufacturing sites. And now the U.K. just announced the deal themselves moving towards the amount. I think it was yesterday, they announced that they were going to move from 0.3% to 0.6% GDP, which is what the Americans are expecting but as part of the overall trade deal.

What it means to making budget available over what time line for PhRMA, I don't know. Do we want to continue to do clinical research in studies -- have studies in countries where the medicine will never be available eventually? There's a little bit of a moral crisis for us in that. So I think Trump has forced a debate in Europe about your question, spend more money or not for the first time at scale that I've seen since I've been an executive.

Where it nets out? Not sure, but some countries you feel smell opportunity versus others. That is for sure. And you can see that with our heads of state and Ministers of Finance are talking to me and others like me. And if that leads to access to medicines that didn't exist before, that's a win and the President deserves some credit for forcing the conversation.

Got it. Okay. Excellent. Just one last point. As we think about some of the price points on TrumpRx that companies are agreeing to as part of their settlements, my sense has been that those price points are largely irrelevant because the cash pay volume is always so small because our employers will only pay for what the PBM contract is structured by the insurance company. So the insurance will never pay for TrumpRx. Is that consistent with how you look at it from your commercial experience?

Well, I think if we look at the medicines that are going to be there or medicines that we could consider being there, these are reasonably low-priced medicines where the out-of-pocket cash play is manageable for a patient. And all they're doing is forgetting the insurer. And obesity is an interesting one as a starting point. That captures everybody's imagination because -- of course, people living long is very important.

Vanity is also a major driver of people deciding to spend a couple of hundred bucks out of pocket. That drives this huge level of noise around direct to consumer. But actually, the scale of how many patients that will impact outside of obesity is quite small. If you are on $30,000, $40,000, $50,000, $80,000 specialty care med, where are you going to -- where does that go without the insurer being involved? And how do you pull the insurer in?

Not sure at this point. If you're Amazon and you bought PillPack and you have all these options and you can ship medicines, I don't see you trying to interact with insurers to try and make it all possible. So if it stays cash, if it stays cash, it's going to be lower priced, older medicines or price of medicines that got forced down maybe via politics and other things to be made available. So don't see the issue, waiting to see the big opportunity.

Excellent. Excellent. Maybe last policy topic before we go to more Sanofi-specific topics. Where is your thought process from the recent FDA updates, the weekend e-mails, all that stuff? How do you see that evolving? And do you see opportunities within that?

Well, I just saw, I ain't had it confirmed though that Pazdur has just resigned.

Oh, is that right? I didn't see that.

Look at that? I mean on the news.

Oh my God.

Put that in the podcast.

Yes, I'll take that.

I just read it in the news feed. So somebody will confirm whether it's real or not. And that's just after recently Tidmarsh had gone in different reasons, I would imagine. And so there's a lot of musical chairs going on. And we spent a bit of time with Makary. And I have to tell you, every time I've spoken to him, he makes sense, it's common sense. We want to be making these medicines available.

We've been too hesitant. Everything he says is, I think, gives you a lot of encouragement and positivity. But that will be the second -- no third CBER director since Makary, is that right? So that's -- we have to decide what that means for continuity of programming and delivery, and we would hope that it is maintained in the relevant director and things, but it's a lot of change.

What about Vinay?

Well, I mean, as I said, there's a lot of change. There's -- I try and choose my words a little bit carefully, but I think we need a tiny bit of stability. We need -- we have all of this drama with vaccines. We have all of this drama now with CBER. Do we really know what the new FDA looks like and how they operate.

I guess let me push it to an extreme, and now I'm kind of venturing right into some of a core Sanofi base business topic perhaps. Do you see either increased -- meaningfully increased R&D costs or perhaps annual recommendation issues for your flu franchise with some of the stuff Vinay proposing?

The flu coverage rates are down. And I've had my own conversations with us, with Kennedy, with everybody about what this means. I spoke very candidly with Kennedy about MMR and the measles outbreaks and what does it mean? He was very explicit with me. He doesn't see any responsibility in any of that. He sees that it's our job to do our job better. We have the conversation about herd immunity and about the importance of these things. And it just -- it's not a productive conversation. There is stubbornness around some of these subjects, whether they believe they're correct or not.

Now we're not in the mRNA, we're trying to be. We're in -- we bought the COVID-19 vaccine from Novavax for really a sweet deal to be fair, and perhaps the last vaccine that will ever be available for COVID certainly in the United States and the only non-mRNA vaccine. Now it's funny with the administration, there is a sort of anti-vax sentiment, there's an anti-mRNA sentiment. There's a few sentiments and then there's the public own literacy on whether they think mRNA, the reactogenicity is too painful, be sick for 2 days to avoid being sick for 4 days.

And so for us, we think we may just come through '27 into '28 with a flu COVID single shot that's non-mRNA that may just be perfectly timed given all the drama around it. For everything else, Beyfortus got approved. Beyfortus goes from strength to strength. It won't be far off a $2 billion drug.

Beyfortus, does it fall into Vinay's vaccine category or not?

Well, it's a funny one. I never thought, I'd have some of these conversations, but it falls into the immunization category.

It does?

To me.

To you, but to him. I mean because there's a bit of a political angle to it. Vaccine versus antibody is different treatment.

There is. And I can tell you with Beyfortus, which is for RSV, one of our biggest rate-limiting steps when we were forecasting before launch was our issue was it's not a vaccine. It's a monoclonal antibody. And we did quite a bit of market research. This is just with parents of newborns. And we thought we would have an issue because it wasn't a vaccine. What turned out in the end to be one of the reasons for the fastest uptake was that it was a monoclonal antibody.

And the parents decided we can stay out of the fray on the vaccine debate because it's a mAb and really, it's just common sense. We never thought people would grasp any of that. There's a big debate and we saw it when we were coming through with the guidelines and whether we'd be included even in the debates in the last round of ACIPs that never happened was where do mAbs fit. And they seem to be lost in a good way so far.

You don't want to be in the headlines for this stuff. That's great.

I don't -- I think if more babies get protected because we're out of the headlines, then that's better for all of us, right?

Great. No, no, that's fantastic. Okay. So it doesn't sound like -- I think on your vaccine business broadly, including Beyfortus, it sounds like headlines may not be ideal, but you're not as worried. You sound reasonably comfortable with that.

I don't think any of us like that they have some commitment to public health, the drama around choose for yourself because that's not really what I think should be coming from HHS. I think there should be -- it's the duty to try and protect as many as possible. The debate around the safety of vaccines is always a handful of patients over here or healthy people that had a tragedy versus the millions protected.

And it will never be that square -- we can never square that circle for the people that don't won't spend time to read it. If you just want to be on Facebook, you're going to get what you get, and we'll see where it goes. I can only talk about the Sanofi impact. On RSV, we're doing great. In flu, flu coverage is down, but market share is up with our high-dose flu. The over 65 still want to get protected. They still want the best because they're the most at risk, in the sort of 40 to 60 range, people are saying, you know what, maybe I'll take a season off or maybe I won't bother or maybe it's not as bad as I thought and I will -- I may be sick or I may not.

And that's where we see the volumes changing in who's stepping forward. I don't think that's good. I think it is what it is. I think by '27, we have a flu COVID and it's a 2 in 1, those headlines beat coverage rates. So that's it.

Got it. So maybe turning to pipeline, and I know we have your former Head of R&D here as well. So I'll keep looking at you and him. I'll gauge 2...

So Reeds in the house.

I'll gauge 2 body languages on each question now. But tolebrutinib, PDUFA coming up, there are a few set of liver cases and they're real liver cases. I guess my question is, what has the regulatory conversation been so far? And what's the expectation, both on approvability and on label?

Yes. I think the conversation while everybody fixates on the PDUFA, we were going to get an accelerated review. We're now back on the original time line, if you like, for December 28. I think what John, the team, myself, but to a lesser extent me, put forward 5, 6, 7 years ago was to do something first-in-class, best-in-class in the secondary progressive MS that has no treatments.

And we didn't think it to be without consequences. We would hope that it wouldn't be. We had some DILI in the program. We changed the protocol. We went to weekly monitoring for 90 days. And we had no Hy's Law or significant irreversible DILI after that point. So we know we can manage it. The question is, what does the FDA think about the risk benefit. And we simply don't know. This is a huge unmet need, and we delayed disability progression by 30% in an area where there are no drugs.

So that's pretty outstanding. But the FDA will, of course, always want us to show that it can be managed safely. Perhaps in a previous regime, that would have been an AdCom, right? That would have been -- that's where you bring the patient group -- the patients. The patients will tell you because they tell me, we would take that shot every day of the week because what's our choice from cane to wheelchair. We want whatever we can take at that point.

And as long as we understand the risk and we monitor it, monitoring is not uncommon in MS. We would take it. That may not be an option for us. We will go through -- they've asked for the GEMINI data to look at the safety and efficacy, which is our relapsing remitting data. We didn't beat Aubagio on relapsing one event every 8 years versus 1 event every 8.5 years.

But on disability progression, we were significant in that group. So there should be enough for them to see. They also -- we also have the primary progressive data just around the corner imminently. And what will that tell us versus fenebrutinib and their noninferiority, we're against placebo, so we may win. Where does it leave us with the FDA? Active conversation. We're already now then on our third head of [ CDR ] as part of that CDK, which the office is meant to be the continuity. And so we hope that's...

So is the news you broke or is that a good news or bad news?

Well, it depends if we get approved or not. I think the systems and process and the rigor is the same irrespective of the head of the office. I guess if we felt like we needed to appeal or something else, you'd rather have some continuity. Right now, they have the data. We've very open conversation. We have to get to the label conversation and get to PDUFA and see where we go. I remain optimistic on it.

Can I summarize how I'm hearing this?

Yes.

It sounds like -- the way I'm hearing it, and I'm not covering Sanofi analysts, but the way I'm hearing it is it doesn't look like this is a situation like Biogen aducanumab where leadership level at FDA was getting involved in overruling a decision from down below. It sounds like -- you said you're reasonably comfortable on how it's tracking. It sounds like the lower level review is tracking in favor. So you're actually not as worried about the leadership having the stuff in that stage.

Yes. I didn't say it was tracking in favor. I just said it's tracking. And so the -- I don't think it's as sensitive as some of those other examples that you gave. But it's our job, my job to track alongside senior leadership just in case a candid compensation is needed. We will see with the office where they get to. So we have an unmet need. We have incredible efficacy data, and we have to be managed safely through a REMS for the first 90 days at least.

That is not a sort of -- that's -- they have to weigh that up and how they feel about it. I don't think that changed. When they -- we were on track and then they ask for the GEMINI data, I think it's because they generally are trying to find how to properly characterize the population. For me, that is patients who haven't relapsed for 2 years and are still progressing. That's quite a big population. That's 25% to 30% of the MS population.

So I can't tell you positively or negative. I can just tell you, the dialogue is as professional as it's always been, and we'll wait and see what the politicians...

Was the liver data better in GEMINI versus -- or it doesn't matter. It depends on when the amendment was done.

It's after the amendment, everything got done.

Excellent. Paul, over time, one of the things I found is you're very good at like first principles way of thinking about commercial opportunities, almost like a very reductive way of thinking. How do you think about the opportunity here for tolebrutinib?

If we get through and we get no lapses for 2 years, and we're in the 25% to 30% of the population, that's SPMS. I told this to a few people already. I'm not interested in launch uptake. I'm interested in perfect REMS, perfect REMS for the first 12 years -- 12 months. And then everything we learned to do white glove thereafter. These patients need the medicine. These patients are valuable to us, of course.

We can afford to do perfect REMS. So I think it's extremely valuable. We're the only drug that's ever shown anything in this disease. We're the only drug. If the other BTKIs have a go, one may, it's 5 years late. So we have the opportunity to do it correctly and be a multibillion-dollar drug in SPMS and do great things for patients. Got to get the right label, got to get approved, yes, got to have perfect REMS, yes, more than manageable if we get there.

Okay. Has the company put out numbers on this?

Well, I personally put out numbers. This is the IR...

Can I put out -- throw a right number out? $5 billion plus?

Well, I think that we -- I think if the label is broad enough and we get primary progressive, I think you could be talking within that range. But we need perfect REMS. I've been around long enough in MS to see when you get a case of PML, how people's attitudes change so fast on a PML. You were the golden boy or girl of the drug treatments without a PML. As soon as you got one, you were quickly put in the class with everybody else. I don't want to have any of the drama around DILI.

That's why being perfect on REMS and monitoring will be so important. And I think that can be done. Certainly, in secondary progressive, $2 billion, $3 billion. If you get primary and perhaps over time, you can creep a little bit earlier, maybe it gets towards the numbers that you're saying. I'm not worried about the peak. I just want to get approved. After that, we will see what we can do and we'll do it skillfully.

Fantastic. What about frexalimab sticking to sort of like the same market, your thoughts on sort of when is the Phase III readout? And what type of a commercial opportunity is that in the context of OCREVUS that's already out there?

Well, I think OCREVUS has done a great job, but it really has no impact on disease progression, great on lesions. The hypothesis you know around the CD40 with frexa is that it acts both on disease progression and lesions. We can argue the efficacy data in lesion is so good that it's sort of a nonevent. The question is really, do you have an underlying impact on disease progression.

I get emotional when I talk about frexa. So the bottom line is if you work on progression and lesions, then that's sort of the holy grail. For a while, we've been thinking about putting tolebrutinib with frexalimab. The more we understand about acquired innate immunity with CD40, the more we think we can do something for those that are progressing on top of the lesion, in which case, it has a huge opportunity.

Don't forget, we're also going to take it into type 1 diabetes, and we have a good opportunity there to try and protect as much of the islet cell function as possible that's left. So we think it's a great all rounder, but it may be the only drug that does relapsing remitting and disease progression safely without the risk of infection. And I think that it has a huge place.

Right. Okay. Excellent. And there was a couple of cases of liver enzymes I saw on this, which was kind of unusual, but I didn't know necessarily if that's drug-related or not.

Well, I don't think we do either. I think it resolved. So we leave that for what it is at the moment, and we're continually adding more patients in the study. So I don't think it's -- at least from what we know and specific to the medicine.