European healthcare specialist sales at Bank of America. Today, I'm with Manuela Buxo and Elizabeth Laws of Sanofi. So they're gonna start off with a quick intro, and then the omnipresent voice you're gonna be hearing is Graham Parry, our European research analyst, who's gonna be leading the Q&A. In any case, you do have a question that pops up throughout the Q&A, I'll be up here kind of looking for any hands to call on you in case you do wanna ask a question during the presentation. But that, I'll hand over to Manuela. Thank you very much, and thank you for joining us, and thank you also for those that are joining us online. My name is Manuela Buxo. I'm the Global Commercial Head for Dupixent and itepekimab, and I've been with Sanofi for almost 10 years now, across a variety of commercial leadership roles. I'm joined here by Liz Laws, who is a fearless R&D leader and the Global Program Head for Dupixent, and really somebody that has created the playbook for Dupixent together with her team. We're really excited to have this session with all of you today. As you've heard, in our Q1 earnings call, Sanofi is off to a great start, 7% growth in sales in Q1, which is driven by multiple launches, including, of course, the new and existing indications on Dupixent. Dupixent continues to grow very strongly in demand, and that is driven by, of course, U.S. demand growth, but also ex-U.S. demand growth. EUR 28 billion in sales in Q1, growing 25% versus previous year. Ex-U.S. growth has accelerated to over 50%, driven by indication expansions, and we now have 850,000 patients on therapy with Dupixent across the world. And the growth that we see, especially in markets like Germany, Japan, and China, shows you how much potential there still is for this brand to further expand, given the highly under-penetrated spaces that we're in. Dupixent is, of course, the foundation of our immunology pipeline, and we're very excited about the pipeline that we are building. We have a bold ambition in the I&I space, and we believe there is a lot of opportunity for growth still in that space. It's a highly under-penetrated market. We know how to succeed in this market, and it's not just about meeting the needs of patients that are already on therapy on immunology treatments, but it's really about the opportunity to expand penetration into... or expand the penetration into innovative therapies and large patient populations that are eligible but are not yet on advanced therapies, and that's what we are here to do. And of course, the starting point of that vision and that ambition is the transformation journey that we've been on, especially on the science side of things. And I'm handing it over to Liz to talk a little bit about the progress on Dupixent, but also on other I&I assets. Thank you, Manuela, and thank you, and hello to everyone in the room and on the webcast. It's very echoey. So, as Manuela mentioned, I've been with Sanofi R&D, leading Dupixent for the last 9 years, actually. I've been with Sanofi R&D overall for the last 14 years, and I've actually seen us build Sanofi I&I into an industry leader. As mentioned, we sort of wrote the blueprint for building a multi-indication and a blockbuster, and we continue to refine that blueprint, and we're doing it faster and better with our new assets. We continue to have a constant, steady news flow with our I&I assets. As you saw in our Q1 earnings, for Dupixent, for COPD, we filed globally, for eosinophilic esophagitis, we had the U.S. approval, and for chronic spontaneous urticaria, we got our approval in Japan. For amlitelimab, we showed the new phase IIb data, showing potential for best-in-class efficacy, for maintenance of response in atopic dermatitis patients. And then for rilzabrutinib, we saw the positive phase III data in ITP, as well as encouraging data from the asthma high-dose arm of the asthma phase II trial. I'll reiterate what we said at R&D Day. We have the right assets, we have the right strategies, we have the right people, and support from all levels of our organization to really deliver on our ambitions for our programs. So I'll turn it back to Manuela. Yeah, and we're gonna get right into the Q&A, but you know, given the strong Q1 results, given what we're building, of course, we're convinced that we will hit the EUR 13 billion target that we have given for Dupixent for this year in terms of net sales. And we're also very excited about the transformation journey that we've really gone on as a company, end-to-end transformation from targeting all the way to launch. On Dupixent alone, we will launch at least, hopefully, at least 8 new indications, including COPD, as Liz was just saying. And we're also excited about itepekimab, which complements very nicely, the COPD Dupixent franchise. We can talk about that a little bit later. We're really excited to answer all of your questions, and I'll hand it back over to you, Dominique. Graham, we're ready to start the Q&A. Great. Thanks, guys, and thanks, Manuela and Liz, for that, and thanks to everyone in the room. So if we could just actually kick off with the rough contribution you're seeing on the commercial side to the growth and how across the different indications, how much of that's coming from AD, eosinophilic esophagitis, nasal polyps, et cetera? If you just help us understand where the growth is coming from now. Absolutely, Graham, and it's nice to hear your voice. So on contributions, we're not gonna, of course, give indication-specific details. However, what I can tell you is atopic dermatitis is, of course, our most important indication, will remain our most important indication. We've previously communicated that on atopic dermatitis, as well as asthma and nasal polyps, we have reached blockbuster status. For other indications, PN has been communicated as one of the most successful launches in dermatology. Eosinophilic esophagitis has also been a very successful launch, and we will continue to grow across all of these indications over time. As I mentioned earlier, all of them are highly under-penetrated areas. We're talking in AD across some major markets, around 9%-10% biopenetration. So there's still a large part of, the eligible patient population that is not on treatment. On asthma, that is, slightly above 20%, right? So, in the U.S., it's a little bit higher 'cause we've been on the market for longer. But, there's so much opportunity for growth in those indications, and at the same time, we also need competition to help us grow the market. There is space for more than one product. There needs to be more than one product in those spaces because to some extent, they're also heterogeneous patient populations. So looking forward to more growth in those spaces, but, but definitely a lot of things have already been achieved. Got it. And in AD, I think you touched on the penetration in the U.S. How, where do you think that can get to over time? And if you could actually address the fact that more of the growth now, if anything, seems to be coming ex-U.S. So just the timescales on increasing the penetration rates. So I think you'd said mid-single digits across most European markets, and what drives that up? Yeah. So maybe first, your question on, you know, AD specifically. So in the U.S., we are still below 15% biopenetration on atopic dermatitis, and we expect that to double. You can see that in other areas that are more mature, that have had, like rheumatoid arthritis, psoriasis, that have had biologics for a longer period of time. And we definitely believe there's a lot more room for growth in AD, and as I said, the other indications as well. When I look at the accelerated growth, ex-U.S. versus U.S. growth, first of all, let's remember that even in the U.S., TRX growth was 25%, NBRX growth 22% in Q1, right? So there is a lot of growth in the US, but ex-U.S., it's simply a timing question, right? We have launched several indications later, in markets like China, for example, where we currently have atopic dermatitis launched. We just got approval for asthma in November 2023. We're looking forward to hopefully launching COPD there, but you can see that, we are ex-U.S., a little bit more delayed in terms of when do we launch, new indications and also, when do we launch, demographic expansions, into younger populations. So that's what's driving, more accelerated growth. But across the board, demand growth is very, very strong. Got it. Thank you. And, when do you start contracting for 2025 in the U.S., and do you think lebrikizumab is gonna be coming into those conversations, given, the expectation that it should be approved before the end of the year? Yeah. So I think in terms of contracting, we are in the midst of contracting for 2025 as we speak. And in general, we have a very, very favorable payer coverage, as you know, right now, and we have a very robust long-term access strategy. So we have anticipated competition coming in. We have anticipated indication expansions, new indications coming in. So that has always been part of the mix. And overall, of course, you know, if you are expanding through new indications or if competition comes in, it will create some pressure, again, that has been planned for, but at the same time, it also helps you grow the market and helps you grow the overall pie. So that's just part of the game, and it has all been planned for. And we really, the long-term access strategy is all around profitable growth for Dupixent, and I'm very confident that we can continue that and achieve it. Yeah. Got it. Okay. And then, in terms of where you see or expect to see the new biologics coming into the market, so you've got lebrikizumab, but also, likely the IL-31, nemolizumab from Galderma as well coming in. Do you see those as being competing for, you know, de novo patients, or do you think Dupixent will retain the bulk of them, and these are gonna be used as second-line agents in patients not getting optimal outcomes on Dupixent? Yes, I can ask, Liz, also to talk a little bit scientifically how they compare, as molecules. I think at a high level, I would say, first of all, as I reiterated at the beginning, the more players in that market, we've seen it in psoriasis, we've seen it in rheumatoid arthritis, the more players, the more it helps us grow the overall market. We need to grow biopenetration in those markets, and one product alone cannot do that? So we always welcome competition for that reason alone. When I look at lebrikizumab, for example, and Liz, please, you know, correct me if I'm wrong, but it—we always look at it as an incomplete product. You know, it's it... Dupixent will continue to remain first line. It has a very established efficacy and safety profile, safety data, real-world evidence for more than five years. Lebrikizumab is an IL-13, but misses the IL-4. It doesn't. It's not differentiated from Dupixent. So yes, it has a space in the market, but Dupixent will continue to be the first-line treatment and will continue to be the market leader for sure. And the same with Nemo. When we look at the results, you know, it's we have very strong itch data on Dupixent, and when we look at PN, for example, it's undifferentiated. When I look at the efficacy data in AD, I don't think it's that impressive. But again, more players help us grow the market. They will have a share of the market, but we will definitely remain, a key player. Anything, Liz, that- Yeah. No, maybe just one thing to add. You know, we like to say that we're a pipeline and a product, and so of course, we have had more type 2 diseases approved, and both lebrikizumab as well as IL-31 have not really expanded beyond the dermatology space. So sort of in terms of, you know, overlapping diseases, type 2 underlying type 2 inflammation, driving your overall systemic course of your presentation, you know, I think there's opportunity there for us to really differentiate. Absolutely. Great point. Got it. I just wanted to move on to COPD. I'll ask about commercial opportunity first, and then, I'm sure that I or others in the room would have questions on regulatory pathway as well. When you talk about the 300,000 U.S. patients with type 2 COPD, could we just clarify how you define the type 2? Because I think in the sort of pre-phase III worlds, you actually used a fairly broad number of things to define it, but the phase III trials just looked at is eosinophils greater than 300. So is that 300,000, is that effectively what you see as the... is eosinophil greater than 300, cells per microliter, population, or is that a broader population that have other things like bronchodilator reversibility, for example? The patient population is pretty clearly defined also in terms of our clinical trials. It's the GOLD-E population with an EOS higher than 300, as you say, Graham. And this is exactly the 300,000 population that we have looked at, right? If you look at E.U. five, Japan, and the U.S., it's 1.7 million patients that are uncontrolled. GOLD-E patients with an EOS higher than 300, and for the U.S., that's the 300,000 patients that you're talking about exactly. Yeah, got it. Okay. And in terms of accessing that population, once you're commercially approved, do you see that you're already effectively addressing most of the prescribing community through the asthma indication, and this is just a matter of education around getting people to do eosinophil testing in COPD patients, or do you need to actually add any commercial capabilities? So, I think it's a mix. There's a large part of pulmonologists who we are already visiting that know Dupixent very well, because of our asthma indication. And of course, it will be easier to talk to them about COPD because they have experience with Dupixent. There is a population of pulmonologists in the U.S. that are, you know, really focused on COPD, so we will have to educate them. And then in general, I think we have to educate around EOS testing in COPD, right? It is something that, given the heterogeneous patient population in COPD, it is important that the type 2 patient is clearly identified. So that's the work that we need to do. Working on really identifying what is that patient clearly, what's that patient profile? How do you identify it? But given the urgency to treat, let's remember, COPD, the third leading cause of death globally, 150,000 people in the U.S. alone die every year from COPD. It is a significant healthcare cost burden as well. So there is a real urgency to bring patients and get access, give those patients access to treatment. Having said that, though, we need to educate patients. There hasn't been innovation in this space similar to what we've seen in the atopic dermatitis space for almost a decade. So we need to educate patients, make them aware that there's a new treatment. We have to educate pulmonologists, and we also have to create access, broad access, which is our ambition in this space. So, we really see, an inflection point in 2025 for COPD, assuming that we get approval, of course. But, there's definitely an urgency, and at the same time, we're very clear who we are treating, how do we need to, create awareness, and how do we need to educate. Got it. Okay. And then just on that, you talked about the sort of different pulmonologist bits. So the target prescriber population, how many, what proportion do you think you're already addressing, and what proportion are those COPD specialists that you will, I guess, need to educate de novo? I think we are addressing already between 70% and 80% of the pulmonologist population. Specifically in the U.S. Got it. Okay. Yeah. Great. And then perhaps if we just shift on to the regulatory party, you said that it if approved, and there's obviously been some to and fro with the FDA. So Regeneron said on their earnings call that the FDA had requested additional data on subgroups or subpopulations. I think they most recently said that they do expect the FDA to review in time, but just it'd be useful to get your sort of commentary on what it is that the FDA is requesting. And is the concern here that the efficacy is being driven by a narrower group than the EOS greater than 300? So, you know, are they looking at a narrower subpopulation here, or were we looking at the potential to actually have a broader label? Yeah. Maybe I'll start with, you know, as you know, BOREAS and NOTUS we're to replicate a highly positive statistically significant and clinically meaningful studies in COPD patients with the eosinophilic phenotype. So we're very excited by the results. You know, as is usual with the agency, we go back and forth with discussions with them in terms of analysis of data. As you were well aware, during the review, we had submitted some additional efficacy requests from them. We're not discussing specific subpopulations at this moment, but we can rest assured that all populations that have been analyzed have seen consistent and clinically meaningful results. So we are we continue to remain positive on the overall filing. And we will see in the we still have PDUFA for June 27 at the moment. Got it. Okay, I think the indication that you filed for is COPD with type 2 inflammation. I noticed on their call, Regeneron referred to it as eosinophilic COPD. Is there a subtle difference between the two? So we studied a patient population that has screening eos of 300 and above. If you take a look at some of our publications at baseline, about 40% of them fall below 300. So, you know, I think for us, type 2 is sort of, you know, there's no set defined cut point for that. So, you know, type 2 is more descriptive of the patient population. But, you know, eosinophilic is sort of what we studied, so we'll see where we get with that discussion. Got it. Okay. If it was in a description or the label included is eosinophilic, do you see that would limit the commercial opportunity or patient population in any way at all? No, we don't. The same population that we talked about earlier, Graham, the 300,000- Yeah. -would be the same population that we would consider for that label. Got it. Okay. And then just remind me the timing of data submission of what they've requested, and when you would actually know if this is a major amendment, and if you do have a 90-day delay or not. I think Regeneron indicated on their earnings call that, you know, the deadline for the response was end of May, and that we would be responding soon ahead of that time. So we will hear, I guess, after at some point between now and June 27th, I guess. Got it. Okay, and I guess your in the event there is a 90-day delay, is there anything that would change in terms of your commercial strategy or, you know, cost allocation, or is effectively the cost, most of the cost allocation for launch, already in place? So, nothing you could sort of do to pull back on launch costs, for example, just for a quarter or so. Yeah. No, I don't think it... I mean, on the commercial side, it doesn't change anything. I think it just makes us even better prepared. You know, the teams are fired up, ready to go. So whenever the FDA gives us the green light, we will be ready to launch, but it doesn't change anything on the commercial strategy side. As I said earlier, you know, for us, the inflection point was always 2025. You know, this is a year for us to build awareness, to educate, and this was always the plan. And also, as I said earlier, to create broad access, so that patients can get access as quickly as possible. So none of that changes, Graham. Got it. Okay. And then just timing of global launches. So you touched on China, for example, but just remind us, when do you expect to be able to commercialize in Europe and then in other major markets like Japan, China as well? Yeah. So we have submitted in Europe, as you know, and China and Japan as well, and other geographies. So we are expecting to hear back in Europe by the end of this year. Same in China, and Japan will be a 2025 launch. Got it. And then for the Chinese opportunity, obviously, COPD is very prevalent there. Are you thinking of this as being a predominantly private pay market, or do you think this is gonna be an RDL-listed drug, with, I guess broad volumes but lower pricing? So, we're still reviewing our RDL strategy for China, including, of course, the newly approved indication in asthma, which hasn't gone through RDL negotiation, as well as COPD. So we're discussing that internally. We will discuss it also with the Chinese authorities to make sure that we put our best foot forward. And as I said earlier, you know, the asthma launch has been really encouraging in China already, despite the fact that it's fully out of pocket at the moment. So, I think we'll leave all doors open at the moment, and then we'll make the decision once we hopefully get approval. Yeah. Got it. Okay. Dom, just wanted to check, actually, is there any questions in the room, 'cause we're running close to the time now? If anybody has a question, feel free to raise their hand. No, Graham, you can go ahead. Great. Happy to keep going. Okay, so, I actually wanted to shift across to CSU. So just update on third study timing, filing, and just remind us why FDA wanted that third trial. What was the shift in strategy? Yeah, maybe I'll start there. We are on track for the readout of the third trial in the second half of this year. The third trial is a replicate of the first trial, which was in antihistamine non-responders, as well... uncontrolled patients on antihistamines, as well as omalizumab-naive patients. The second study had a slightly different population. It was in the omalizumab non-responder population, so a more intractable population than Study One and Study Three, or Study A and Study C, as we call it. We were positive, and we did see positive trends across all of the endpoints that we measured, but it wasn't statistically significant, so the agency just wanted another replicate study that was positive. And maybe- Got it. And how important do you think CSU could be as an additional indication, just considering size of the population, but also, you know, there are other agents that are starting to show data in that setting as well now? I'm not sure I understood the question, Graham. I'm sorry. Can you repeat it? Just so, yeah, just sort of how important an indication do you see it in terms of incremental growth for Dupixent? So do you think it should be, it could be something which would drive a notable or noticeable inflection on launch? And also it's an indication where there's, I guess, an increasing competitive dynamic from the BTK inhibitors potentially coming into that market, remibrutinib seeing positive phase III data. So how do you see this as a sized opportunity for Dupixent, and how important is it? Yeah. So I think in general, when you look at the eligible patient population in CSU, it's quite a sizable patient population and similar to other indications. You know, there's still a lot of naive patients out there that are not yet treated. So there's definitely an opportunity to capture that market. Let me remind you also that we have launched already in Japan in CSU, and the launch is off to a really, really strong start. In terms of competition, to your question, again, there's definitely space for more than one product, given also the heterogeneity here. I think the one thing that Dupixent has going for itself is obviously the very proven safety and efficacy profile that we have. There is a real opportunity to get dermatologists, especially in the U.S., comfortable with prescribing CSU because the current product has a black box warning, and they tend to send their patients to allergists. So there's a real opportunity for us to again work in a synergistic fashion at the dermatology office across now several indications. And also we have additional readouts, right? We have CSU, we have BP reading out and CPUO later this year. So there's a real opportunity for us to have a strong portfolio play from a dermatologist perspective, hopefully in the future. Great. Okay. Just in the last few minutes, I think it's worth, I know, given Elizabeth's background in the sort of broader I&I portfolio, maybe perhaps just touching on a couple of other products. Staying with COPD, itepekimab. Just perhaps you talk through the competitive profile that you see for itepekimab versus the other two IL-33 or ST2 pathway agents reporting phase III data next year as well, so from AstraZeneca and from Roche. And how you sort of see that market developing, and where these assets should sit versus Dupixent, do you think? Yeah, no. So, so thanks for the question. So, both itepekimab and Dupixent together will cover over 80% of the GOLD population, so we're very excited to have itepekimab join the overall arsenal. You know, in terms of comparison to the other competitors, you know, we did a very robust phase II study with 350 patients or so. We saw a very strong signal in the former smoker population, which is a population that we're taking forward. Tozorakimab did not have prior data, so, you know, we'll see how they manage the inclusion, exclusion criteria, as well as sizing up the efficacy. And then similarly, astegolimab did not... It had a very small phase II study, but, you know, as you saw, they had to add another dose arm to their phase III trial. So we're still leading in that. We anticipate the readout next year. We're very excited for it. I think it'll really, together with Dupixent, be a very nice complementary story and dominate 80% of the market. Exactly. And, Graham, as we previously have said, right, the opportunity here is larger than EUR 5 billion in peak sales across both Dupixent and itepekimab for COPD. So as Liz said, very excited. First, and best-in-class opportunities for both in COPD. So we're really, we can't wait. Got it. Okay. And then, on amlitelimab, I guess, where do you see the profile of that product fitting in alongside Dupixent? Do you still see this as a likely to be something which goes off to bio-naive patients as well as the Dupixent failure population? So I think on the one end, and Liz can talk about the profile of the drug. We're really excited about it from a durable efficacy perspective as well as from a dosing opportunity perspective. I think as I said earlier, you know, when you look at any analog, like the psoriasis analog, for example, there's so much opportunity for different products and different brands to coexist. Atopic dermatitis is a highly heterogeneous patient population, just as an example. I know we're studying it in multiple indications because it's really a portfolio and a product yet again. But I think in AD in particular, we are gonna maximize Dupixent until the very last day, that's for sure, together with our partner, Regeneron. And at the same time, there's definitely a space for a drug like amlitelimab and some of the other pipeline products, some of the oral products that we have in our pipeline as well, to play a role, in this space. Because there are different needs, different patient needs, different, expectations as well. So we really believe there's an opportunity to maximize all of these profiles, and we're really excited about the amlitelimab profile in particular. Liz, anything that you wanna add? Yeah, no, so I think certainly the durable efficacy, the acute 12-week dosing that we're studying in our phase III, and then also, as we shared at R&D Day, sort of the phase, the type 1 biomarker reduction, so perhaps, you know, broader capture of- Yeah ... patients that may not be responsive. Yeah. Great point. Not just type 2 patients. Got it. And then to- Graham, we have to wrap up probably after this one. Yeah. So last question, just, rilzabrutinib, you've obviously talked about the high-dose asthma data. In CSU, we saw three times daily dosing being the statistically significant and actually some pretty high GI toxicity, compared to remibrutinib from Novartis. So just your thoughts on how that's gonna get dosed into phase III and how competitive it could be versus remibrutinib? Yeah, so rilzabrutinib, oral selective BTKi, a covalent, a reversible covalent BTKi. So we believe that the safety profile is, you know, is consistent with what we've observed, which would be better than remibrutinib, which has some platelet depressions in their phase II. So I think, more will tell as we go into phase III. Great. Okay. Thank you very much for that. We're on time now, as Dom points out, so I'll hand it back to Dom to wrap up the session. Thanks. Thank you. Thank you. Thanks.