Sanofi

Hello, everyone. This is Thomas Grusazen from the Zenobia IRR team. Welcome to the Q1 2025 conference call for investors and analysts. As usual, you can find the slides on zenobia.com. Please turn to slide number three, please. Here we have the usual forward-looking statements. We'd like to remind you that information presented in this call contains forward-looking statements which are subject to substantial risk and uncertainties that may cause active results to deeper material. We encourage you to read the disclaimer in our slide presentation. In addition, we refer to our new Form 20F on file with the U.S. Agency in our Friends Registration Document, a description of these risk factors. As last quarter, financials reported are under the new reporting scope that excludes the appellate consumer health business. As usual, we will be making comments on our performance using constant exchange rates and other non-IFRS measures. Numbers used are millions of euros, and for Q1 2025, one is stated otherwise. Now please turn to slide number four. First, we have a presentation, then we'll take your questions. We have kept the presentation as shown as in the past, and other companies report today, and we aim at keeping the call to maximum one hour. With Q&A, we have Brian, Olivier, Thomas to cover our global businesses, as well as Roy, our general counsel, and Brendan, head of manufacturing, and Tobias. With the Q&A, you have two options in Zoom. Raise your hand or submit your question using the Q&A function. With this, I'll hand you over to Paul.

Well, thank you, Thomas. Nicely done. And hello, everyone on the call. We had a strong start to 2025 with a 9.7% sales growth in the first quarter. Our strategic focus on innovation continues to deliver, driven by pharma launches, D-PIX and Bayfordus in our vaccine portfolio. Let me highlight our performance of new launches on Flight 6. In Q1, our launches generated €1.1 billion in sales, contributing 11% of the total. This performance was driven by an element of Bay Fortis phasing and expansion in Europe and the rest of the world. Altubio benefited from continued patient switches and has the potential to become our next blockbuster this year. Of note, on March 28th, we obtained FDA approval for Cupipia in Haemophilia, one of three potential launches this year. with initial prescriptions already recorded in early Q2. Moving to side seven, Dupixent. Dupixent delivered strong growth of 20% in Q1, driven by broad-based demand, and reached €3.5 billion of sales. In the U.S., sales were €2.5 billion in the quarter, up 18%. Dupixent now also leads total prescription share across all approved indications. As usual in the first quarter, US sales reflected the impact from the annual reset of insurance deductibles, driving higher utilization of co-pay assistance. Outside the US, Dupixent sales exceeded €1 billion for the first time, supported by the contribution from Japan, China, and Germany. Looking at the remainder of the year, we will continue to drive Dupixent's growth across our markets and in all approved indications. As a reminder, biopenetration still remains quite low, We are excited about the U.S. approval for CSU last week and the upcoming regulatory decision in the U.S. for bolusamphigoid. These additional indications continue to expand our leadership across type 2 inflammatory diseases. On slide 8, let me briefly remind you of the high and met need among people with uncontrolled COPD, many of whom have resigned themselves to their condition. Epipsyn is the first biologic medicine approved in this disease. We have already launched CABD in eight countries, including the US, Germany, China, and Japan. Dupixin's value is being recognized by payers in key countries, ensuring access for all patients. To improve adoption, we focus on two main objectives. First, we continue to educate pulmonologists about Dupixin's benefits, the role of type 2 inflammation, and the urgency to treat patients. Second, to drive patient awareness. In April, we just launched our DTC campaign in the US. Moving to slide nine, our vaccine business delivered double-digit growth in Q1. This performance was driven by favorable Bayport phasing and new country launches. In the U.S., we are focused on improving the immunization rate to ensure infants born in late season are also immunized and protected. Turning to flu, our manufacturing is progressing as planned, following the WHO and FDA strain selection. As the world leader in flu vaccines, we continue to focus on improving the vaccination rate increasing awareness of the benefits of our differentiated flu vaccines. On our vaccines pipeline, we continue to push the boundaries of innovation, pioneering the development of a vaccine candidate for the prevention of chlamydia. In March, the US FDA granted fast-track designation and recognition of our commitment to improving public health and addressing high unmet medical needs. On Friday 10th, I'd like to introduce you to our updated sustainability strategy. focused on aligning health outcomes with environmental and social responsibility. Environmental challenges and human health, an estimated 3.6 billion people are living in climate-sensitive areas, with 6 million deaths reported annually from air pollution alone. That makes it clear people's health and environment aren't deeply linked. Our new air strategy focuses our efforts on three strategic imperatives, access to healthcare, environmental impact, and the resilience of healthcare systems. With over 70% of our portfolio and more than 75% of our pipeline involved in climate-related diseases, Synergy has a key role to play. And through AIR, we are furthering Synergy's commitment to global health by working to break the cycle of environmental decline and declining public health. Thank you. I'll now hand over to Francois, our CFO, for more details on the financials.

Thank you, Paul, and hello to everyone. As highlighted by Paul earlier, our net sales increased by 9.7% at constant exchange rates to 9.9 billion euros. This growth was primarily driven by Dupixent, by our new product launches, and by favorable phasing in vaccines. Growth margin improved significantly to 78% at 2.3 percentage points from the previous year, driven primarily by an improved product mix and by efficiencies. Our Q1 effective tax rate was 22.3% linked to a one-off item this quarter. We maintain our full year indication of a broadly stable effective tax rate versus 2024, which means around 20% for this current year. Business EPS was 1.79 euro, up 15.7%, reflecting our strong sales performance, our improved gross margin, and our operating leverage. This Q1 growth confirms our expected strong EPS rebound in 2025. Moving to Opella, we expect to close the transaction in the coming days. Sanofi will receive about €10 billion while retaining a significant stake in Opella to support the company in its journey to independence and to participate in its future value creation. The expected proceeds from this end will be reallocated in accordance with our capital allocation policy presented on the right-hand side of this slide. First, our primary focus is to invest in our business to drive organic growth, which means investing in R&D, sales and marketing, industrial assets, AI, and talent, just to name a few. Second, we continue to explore external growth opportunities through Bolton acquisitions, In March, for example, we agreed to acquire DR0201 from DrainBio. These promising molecules transcend our early pipeline in immunology. Third, we maintained our progressive dividend policy, and 2025 will mark our 30th consecutive year of dividend increase. Fourth, regarding value-enhancing share repurchases, we are executing our €5 billion share buyback program in 2025, with 76% already completed as of yesterday. We have repurchased 37.7 million shares at an average price of €101.5, all for the purpose of conservation. This underscores our commitment to delivering long-term shareholder value and partially mitigating the dilution from the Opela transaction. Looking ahead to the balance of 2025, I would like to remind you of some anticipated key business dynamics which may be helpful for modeling purposes. For Q2, please note that Lantus USA started to increase materially in Q2 2024 due to the unavailability of a competitor's product, representing a higher base of comparison for the next few quarters. Despite this higher baseline, we expect stable sales for launches in 2025 as we continue to capitalize on favorable market dynamics and competitive opportunities. In R&D, we remind you that we received, in Q2 2024, a wonderful payment from Sobi of about €200 million for the development of Altuvert at the time of approval in Europe. For the full year 2025, foreign exchange impact is moving against us, and it is now estimated to be around minus 1.5% on sales and around minus 2% on EPS. All other business dynamics remain unchanged compared to what we communicated at the beginning of the year. I now hand over to Oumad to provide an update on the progress of our innovative pipeline. Thank you, François.

During the first quarter, we obtained six approvals, including Capitulia, the first antithrombin-lowering prophylaxis therapy for patients with hemophilia A or B, regardless of inhibitors. And additional approvals with Dupixent and COPD in Japan and TSU in the U.S. and Sarkleza across different lines in several countries. Moreover, as Paul has already alluded to, Dupixent was granted priority review in Bullitt-Pempergoid with a producer date of June 20. This is followed by regulatory acceptance of toliprutinib, which is now set for a producer date of September 28th, complemented by two recent New England Journal paper publications. As Francois said, last month we announced the acquisition of BR0201 from GenBio, a potential first-in-class CD20-directed bispecific antibody targeting and engaging myeloid cells. with a potentially favorable and superior safety profile compared to T-cell engagers, which may carry a risk of cytokine release syndrome and other immunological risks. DR201 has the potential to induce deep B-cell depletion via phagocytosis, enabling sustained treatment-free remission in autoimmune diseases such as lupus and where significant unmet medical need remains. Next slide, please. Last week, we shared advances from our mid- and late-stage respiratory pipeline, the amlitalimab, luncecumig, and itopecumab across several indications. The clinical evidence supporting the OX40 ligand inhibition across three major diseases, namely asthma, HF, and AD, is compelling. Furthermore, the efficacy of our medicines targeting this pathway with different modalities is supported by the following data. Preliminary efficacy results show that the treatment with amlitalimab led to clinically meaningful and durable efficacy on exacerbations, lung function, and symptoms in patients with moderate to severe asthma, including in, but not limited to those with heterogeneous inflammation. This limited phase two, four-armed, dose-finding study did not reach statistical significance. The primary endpoint of reductions in exacerbations at the highest base level in the ITT population. As a result, all the endpoints are highly biologically plausible but exploratory. In certain groups, including the subgroup of patients with Pfizer infill and elevated neutrophils, amlitalimab showed a robust reduction of more than 70% in the annualized rate of severe exacerbation of asthma. Amlitalimab is generally well tolerated with no new safety concerns. We and members of some of the KOL community feel that they are very excited by this result. With a relevant statistical caveat that I've already mentioned, I'm looking about this to have a differentiated advocacy profile in selected asthma patients, potentially representing a breakthrough for this underserved population if this result is confirmed in future phase three studies for which we are in the midst of designing. As our early R&D pipeline continues to develop increasingly, I'd like to take this opportunity to shine a light on our versatile nanobond platform. Not only has this produced the potentially best-in-class in asthma drug lunfecimig, but now it's continued to deliver with Brevecumig, our anti-TNF, anti-Ox40 bi-specific in HS. Brevecumig achieved its primary objective with clinically meaningful improvements of both high score 50, the primary endpoint, and other endpoints in patients with moderate to severe HS that are naive to biologics. I'm delighted to observe that the treatment benefit has a competitive efficacy profile when compared to currently approved and emerging methods in HS, with a safety profile and language recognition, and no new safety concerns. These results show the potential to increase efficacy by targeting OX40 ligand on top of the conventional anti-TNF treatment in HS through this dual-targeting mechanism is effect. We have therefore decided to prioritize Brevacumib for further development in HS. Finally, amlotelemab recruitment is progressing ahead of plans in atopic dermatitis from the Phase III studies. The OCEANA program is anticipated to read out in its entirety in 2026 and will provide the foundation for future regulatory submissions. As a result of the accelerated recruitment, the initial results in Trace 1 and SHORE studies might emerge earlier than anticipated. Turning to BALO-TILIFID, preliminary safety results show that the treatment was generally well-tolerated across multiple doses with no new safety concerns being identified. More significantly, this study confirmed its differentiated safety preference. While the primary endpoint at PASID-75 compared to placebo amongst the highest treatment rates evaluated in patients with naive to biologics, moderate to severe plaque psoriasis did not meet the statistical significance due to the nature of this limited Phase II study. Lower doses across naive and experienced patients showed clinically relevant PASID-75 responses. which are comparable to other medicines previously assessed in psoriasis. Our additional Phase II and RAs are anticipated to read out later in the latter part of this year. If successful, we will combine our oral TNFR1 signaling inhibitor and innovative standard of care therapies with the need to increase in the efficacy ceiling. As we've always considered one potential application of this molecule in combination, including fixed-stage combination, we are assessing combination options with internal assay In addition, we're at various stages of discussion with major pharma and biotech partners to generate novel combinations for multiple immune-mediated diseases. For example, with Eli Lilly and Company, we're exploring the potential to combine incretin with sanofi immunology pipeline medicines such as allotunafit. The updates on the progress of our pipeline today support our ongoing commitment to bringing innovative medicines to all patients. It is acknowledged that the study design and the previous strategy were not optimized in all cases. However, the incorporation of this knowledge to enhance productivity is on the way. Furthermore, the progress of new studies exploring lincecumig, its potentially broader use in high-risk asthma, COPD, and atopic dermatitis, and atopecumab in CRS with and without nasal polyps continue to reinforce our pipeline. The FDA's recent approval of Cofitlias and prophylaxis for patients with imofilia A and B irrespective of inhibitors underpins a significant milestone for this community of patients with a unique mechanism of action. Specifically, it's a small, interfering ribonucleic acid therapy that targets antithrombin, requiring only six small-volume subcutaneous injections per year. This approval is expected to contribute to a redefinition of the standard of care with a reduced treatment burden resulting from optimized dosing, complemented by AT levels monitored by Siemens' companion diagnostics. available at no cost with Sanity LabCorp's support program. A regulatory decision in China is anticipated by the end of the year with submission to the EU and Japan expected next year once pediatric data are available. I'd like to conclude with my usual news flow slide for 2025 and for next year. We plan 11 phase three readouts, 15 regulatory submissions, and 14 regulatory decisions in multiple jurisdictions, increasingly capturing the improving value of our pipeline. I would mostly highlight two upcoming phase three results for this year that will be significant. Tolibrutinib in PPMS and itopecumab in COPD. With the aim of launching next year, depending on the data. Next year, I'm looking forward to seeing the results of the phase three data for an improver, our subcutaneous C1 pathway inhibitor. Our objective is to improve the journey of CIDP patients. We've really provided a potential treatment option for those who are inadequately responding or have failed standard of care therapies. We very much look forward to updating you on this progress. As I frequently emphasize, we adopt a humble stance in the face of disease, acknowledging that not all of our efforts will be successful. It is nevertheless anticipated the synergy of skilled science-focused teams in conjunction with our augmented exposure to cutting-edge digital technology will facilitate the advancement of this unique pipeline within our core therapeutic areas with the objective of benefiting patients. I would like to thank all of my brilliant R&D team members and colleagues across the company for the positive progress made this year. We're chasing the miracles of science to improve people's lives. With this, I hand back to Paul for Q&A.

Okay, thank you. We'll now open the call to questions. As a reminder, we would ask you to link the questions to one or two each. You'll be notified when your line is open to ask questions. At that time, please make sure you unmute your microphone or option two, submit your question by clicking the Q&A icon at the bottom of the screen. The question will be read by our panelists. Now, we'll take the first question. Please go ahead.

First question is from Emily Field from Barclays. Emily?

Okay, should we take the next question? Can I come back to Emily if we can?

Okay, so next question is from Richard Vosser from GT Morgan.

This is going to be a quick afternoon. It certainly is. I'll be very quick as well. So a couple of questions, please. Firstly, maybe one just on the amlitalimab asthma data. Obviously, efficacy in these type 2, type 2 low patients. Just thinking more deeply, how you think that efficacy compares to DUPI and really how you think that will read to the efficacy in AD relative to the Dixon from what you can see. And then a second question just on this novel combination, which I think I heard was with incretins and your oral anti-TNF. Just thinking through that combination, should we be thinking about that in HS? Obviously there's a disease overlap with obesity there. Struggling to think beyond that in terms of the combinability. So just thoughts on how we should think about that combination that you're thinking there. Thanks very much. Thanks. Thanks, Richard. Three little sneaky questions across the air, and I'll address all three very quickly. Firstly, on Amelie and Asma, let me start by saying that, as we said at the top of this call, we remain hugely committed to depiction with our partner Regeneron, and we will continue driving that in pulmonology, both in asthma, in CRS and MP, et cetera, and of course in syphilis. So I absolutely would not take a comparison between Amelie and dupilumab. Let me answer your question though promptly. We're very excited by the results we've seen with Amelie and asthma. We've been very clear and cautious that it missed its primary endpoint, but I have to say from where I'm sitting, when you see the data, I feel that in multiple subgroups, we have really very compelling data, which has driven our commitment to getting straight to phase three in subgroups with substantial unmet medical needs. You talked about the hyazinophil group and, indeed, the heterogeneous inflammation group. And in those populations, amitilumab has a distinct place for the treatment of patients, both because of the efficacy in those groups, but also its Q12 doses. So I hope that answers your first question. The second question was related to and combination therapy. As I said very clearly, actually, we said this early on, there would be a small number of indications in which we would go with monotherapy. But we always plan to combine this in combinations. Indeed, even in rheumatoid arthritis today, NTTN is actually combined with methotrexate, which is that synthetic DMARC. So our strategy is indeed to go into combination therapies, including fixed dose combinations. We are in discussions with multiple big pharma and biotech companies. for the appropriate rational conversations, and of course with our incentive pipeline. And your direct question about infrequence, actually there is a substantial body of literature across multiple inflammatory disorders, and we could list them, but I won't do that here, where metabolic contributions to disease are extremely substantial. You'll appreciate that for the sake of uh uh disclosures we won't go into those disorders now but you'll you'll you'll also appreciate we're exploring multiple opportunities thank you uh thank you human thank you uh richard okay next question jess yes next question is from luisa xr from veranda thank you sorry not to find my unmute button um thanks for the call my question's still on um

and asthma, but maybe to go a little bit more broadly because you have other assets in development for asthma. So how do you see it as more broadly a respiratory franchise developing within your pipeline and etc. And then perhaps I could just check on Dupixent, again, respiratory. So a little bit more color on that COPD launch reimbursement status of COPD. and how we should think about that phasing through 2025. Thank you.

Thank you, Lisa. I'll take the first part, just to sign up and then hang to the second part. We've said all along that we want multiple different mechanisms addressing different parts of the patient journey. It's clear that biology penetration, even after all these years, is still in the high teens in asthma, and of course we'll get to COPD. And so we need to have different offerings. So you mentioned the effective negative. We showed data back in 23 at ATS on the pheno drop, which was radically different. And you can see it's starting to shape up how the market could look with high efficacy approaches for those that needed more, longer interval for those that want less needle burden. And then, of course, safety and other elements of efficacy. I think we're very well positioned given the low penetration and the very different offerings for each patient. It's quite a novel approach that we've taken, and we've done this in multiple diseases. I think it's going to play out quite successfully for us. Do you have anything to add on the second part of the question?

Yeah, I'm going to add over to Brian for the launch piece. Just very clearly, remember, in the second egg, we have multiple respiratory populations, including laryngoesophageal asthma. and patients with severe asthma. And we really, really, as you know, with a combination of credential targets, CSRPR 13, shooting for breaking the efficacy ceiling, pretty straightforward. The TPP for that is really very straightforward. I won't repeat the other things that Paul said because I think our commitment from the very beginning was to take franchise areas, to take whole areas, and to provide patients in those areas with the very best treatment we could do and to really begin to tease out substrata. And that's what we've done. Brian.

Thank you so much for the question. And I love that we keep getting asked the questions on CFD. This is really important to these states. It's very heterogeneous like asthma, as a matter of fact. We're just articulating. And we've got a couple of shots on goal, I think, here from the CFD standpoint. But let me first start off with Dupixent. You know, we anticipated always that we'd continue to gain momentum. We launched it at the end of last year. We saw really good progress at the end of last year. But it's gaining momentum even as we started into this year when we still see the inflection point will be in 2025. Actually, we've seen early data suggest that we have a record-setting pace so far as it relates to Medicare and Medicaid coverage or Medicare and commercial coverage, about 90% of Medicare coverage, and at this point, 88% commercialized or covered. So that's really record-setting for the indications that we've had. Additionally, as you look at initiations, we're seeing it's our most rapid respiratory initiation launch so far. Again, these are initiations. They need to turn into NBRXs. They need to turn into TRXs. And that's what we're out there doing now. So we feel that this is continuing to strengthen our position in the pulmonologist offices. It's having a nice play as well with asthma. But again, as we said before, we expect 2025 to be the inflection year for COPD and for it to continue to be a part of many indications now. Our seventh indication recently approved in CSU, but a part of the overall growth that we anticipate will drive double-digit CAGR growth from 23 to 30, generating roughly 22 billion or so by 2030 timeframe. Okay, thank you. Next question.

Yes, let's try again.

Any of you feel, please? Hi, thanks, and sorry for the mix-up before. Anyways, okay, so I'm based Fortis. I was just wondering if you could help us kind of understand or quantify the phasing impact? You know, is there any incentivizing for stocking ahead of a potential competitor launch? And then, you know, in the slide, you also mentioned that you're focusing on increasing the next season immunization rate. You know, particularly in the U.S., what was the penetration of Bay Fortress over last season, and how far do you see yourselves being able to take that up this year? And then a question on Brevacomix. I was just wondering if you could give us a little more color on the synergistic component of the MOA, given that, you know, we know the TNFs alone look inferior to the IL-17s, and then the OX40 ligand, your own monotherapy didn't succeed. So I was just sort of curious why you think that the combination there will look better than each on its own. Thank you.

Okay, so much. Yes, thank you, Emily. Happy to provide a bit of color there. So just to get started, I want to reassure you or anybody that, no, there is no incentive, there was no incentive during the season to stock up B42s ahead of any competition entry. Absolutely not. Now, the color is not specifically, indeed, as you pointed out, on the U.S. market. I'll give you a couple of numbers. I think that can help. If you look at the overall RSV prevention vaccination coverage rate, during the 2024-2025 season, so let's say the month of October to February-March. Roughly in the U.S., there's a vaccination coverage rate which is around 55 to 60 percent, all products included. Of course, the lion's share of that was before this, which is great, and therefore it means that we have more to go, because above 60 percent, you know that we expect peak VCR to be close to the traditional vaccination coverage for infants, so there's room to go, and that's why we're saying that we have a job to do. We need to work on increasing the immunization rate in 25 and 26 to go where it needs to be because all babies need to be protected against the virus. And to give you a bit of color exactly on what we're going to do, I think the qualitative part is important. When we look at the immunization over the past winter, what we saw is that the S community gathered and did a great job at the preventive measures early on, so let's say in the month of October and November, where the right interventions were in place, just got a little bit fading out when you look at the month of January, February, and March. And I think that shows that people have not yet fully understood that it's a full season protection, that babies are at risk when they are born in January, March, and February, February and March, and that's the job we're going to do. this season and the next season. So that's why we're focusing on this. Room to grow there. As for Base R2s for the full year, we've told you last year that our intention is to grow 2025 sets of Base R2s versus 2024. We're still on that trajectory and we're focusing on protecting as many babies as possible moving forward.

Okay, thank you.

Huma, do you want to make a comment on the reckoning? So Emily, thank you for the question on Brecknig. I'll stretch the answer briefly in three parts. One is this is a demonstration of our continuing commitment to internal research at Sanofi. I'm reflecting on the comments people have historically made about research and development at Sanofi. And it's a sort of particular pride for me to bring in innovation from the outside, but especially do work internally. And these bi-specifics are beginning to demonstrate the muscle we have in research as well as development Point two is, you asked the question, why would there be a combination value in those two targets? Remember, of course, the ox40 ligand is a member of the TNF superfamily, as is TNF. We specifically designed the exploratory studies to be able to see whether ox40 ligand alone or in combination with TNF would make a difference. Posing the question that you asked in exactly the same way, And I'm really delighted to be able to provide, you know, albeit early, with all the caveats that go with early studies in patients, particularly biologic night patients, that that combination works. The reason it probably works is that TNF itself induces OX40 ligand on cells. OX40 ligand licenses multiple cells, particularly T cells by denacritic cells. So I really do feel that the double-punch has a precedented biology for synergy. I've got to say, the fact that it really is competitive with best-in-class molecules out there for HS gives me great aspiration as we move forward with these studies. Maybe I'll cut out.

I think I'm going to test on it in terms of It's cool what we're doing with bi-specifics and things. Let's not forget, I mentioned ATS earlier from 23. IL-13 and TSLP phenocrop was in excess of the individual model components. Let's also remember, I think the value for IL-13 didn't work in ASPAR on its own. So it's a red herring to think that because you get good or mixed data on one, you don't get a synergistic effect. There is very definitely something in targeting two pathways, the one plus one equals three. It's the next sort of exploratory battleground for us, and I think we're excited about what we've seen. Next question, please.

Yes, next question is from Chimus Fernandez from Guggenheim. Chimus? Okay.

Yes, Chimus. Hi, this is Colleen. I'm from Seamus. Thanks for taking our question. Is there anything you can share to help us get a sense of your level of tariff exposure to transfer pricing and non-dupixent? Any strategy and steps you're considering that may limit this exposure?

Okay. Thank you very much. Francois, over to you.

Yes. At this stage, we have no specifics to share regarding U.S. tariffs. That said, we have run through all scenarios, and we will communicate in development if need be when the time is right. I would really like to help you, but it is difficult to comment on the occurrence of possible future events that are still unknown or speculative at this stage. So there is no certainty beyond what has been announced, and what has been announced so far has been fully confirmed guidance for the full year 2025. But to go beyond that, would be a little bit complicated because we don't know which country would they apply to, which products would be impacted, which right would be applied, when would it start. So it's extremely difficult for us to comment on a certain number of scenarios, but just be aware of the fact that we are ready and we are fully, if anything else happens, and we are fully factored whatever has been officially confirmed and announced so far.

Thank you very much. Next question, please.

Next question is from Ben Jackson from Jefferies.

Hi, thank you. Just two quick ones for me today. First, just a little bit more on the OX4DL PNF approach. With all that you've seen in HS, does this bridge any kind of confidence that there are additional indications that this combination could be useful for? And does that change the relative positioning that you're thinking about with regards to the broader portfolio? Obviously, we've just mentioned the the OX40L stand-alone there and potentially seeing a synergistic effect, but has this changed how you view any of the assets in your portfolio? And then secondly, just on the TFR1 as well, with regards to the psoriasis readout, has the data that you've seen changed any expectations of the ring-reported arthritis readout coming up? And then with regards to the combo strategy, I appreciate that you've said that the monotherapy was only a small part of the actual opportunity that you were seeing in the first place, but perhaps could you provide a little bit more colour around that and what you see the biggest potential there is for. Thank you.

Okay.

Let me start with Vivekanik. You're entirely right that the combination of Oxford-like anti-anastasis, super interesting. What I won't talk about today is the molecular data we got out of those studies. The molecular data from those studies give us a number of increased leads in what we do. I think it's an unspoken part of being an emerging immunology powerhouse that we have enough internal network strength that we observe from human experiments that we do And it guides us as to where we can drive these molecules through life cycle management. Short answer to your question is yes, asymmetric contrarian insights that emerge from our own data allow us to develop further as an immunology powerhouse. And then to your two direct questions on TNFR1 small molecule signaling inhibitor, the answer to your question is we always knew that psoriasis was a pathfinder indication. What I mean by that is it allowed us to identify the differentiated safety profile tick. It allowed us to establish dosing very straightforwardly tick. And it allowed us to really understand where we would go in combination therapy. There are a number of disorders. You'll appreciate disorders like RA and ankylosing spondylitis that are very TNF responsive, and we may well end up there in monotherapy. And then there are a variety of conditions that naturally lend themselves to combination therapy. I won't disclose those now, but the biology of those is well-precedented.

Yeah, thanks, Amon. It's exciting, actually, in terms of the opportunities, as widespread as it really was at HS. So I think we're very interested to see what the 1 plus 1 equals 3 is. Personally, having been involved with TNF for most of my career, the safety piece in the psoriasis study was the piece we were looking out for first. that was never our target. But the combinations with TNF as backbone, you know, it's interesting the number of conversations we're having externally. There's a great level of interest in raising the efficacy of other adjacent oils to make sure that we can break new efficacy standards for different diseases. That was sort of always the goal and that's now playing out a little bit like that. So, of course, lots of work to do to get there, but I think we're doing pretty positive. Okay, next question, please.

Yes, next one is from Peter from BNPXN. Peter?

Hello? Hello?

Hi there, how are you doing? Peter from BNPXN. Two questions. I'm surprised this one hasn't been asked yet already. Paul? The letter you and Baz penned in the FT does make valid and fair points, but we know governments have big commitments to defend spending increases and not an unlimited budget. So the simple question for me is, have you had any recent interactions with European politicians that give you hope, or should we remain cynical about their appetite to better reward innovation in Europe? And then, Hooman, sorry to sort of labor the point. I know you can't talk about the data, but HS is a big focus for everyone. You know why? So when you are, when you are expressing excitement for pre-recommend, when we finally see that phase two data, we're all going to do cross-trial comparisons to the IL-17. So just want to be clear. Are you saying that you feel the data is competitive to the data sets we've seen from the IL-17As and ANS? Thank you.

Well, I'll let you go first and then I'll mention the letter 15.

Yeah. So, so you may know I was, um, had a cameo role, maybe a bit more of a cameo role in the early days of when I was at UCB, and have an intimate knowledge of that molecule in multiple indications. Suffice it to say that in my mind, albeit early, with all the caveats that you make about small early exploratory studies, it's certainly competitive in relation to those eyes and I'm excited to see how it goes forward in Phase 2B and 3 in due course. Okay, thank you.

As to the letter, you know, we've been, I think, very poised, you know, given China, US, Europe and the state of things in terms of our expectations. I think for a long time, even before the conversations over the last weeks with the change in administration in the US, there's been a long-term campaign to really help Europe understand the value of medicines and investing in them and the quality of jobs and the impact. Very few people really appreciate that the number one exporter from the EU is, in fact, pharmaceuticals, 300 billion plus. We've been public about that. That's been well documented. And I think we have had conversations with the presidency of the EU over the last... over the last weeks just to try and remind everybody of the role that Europe can play in the global pharmaceutical industry. And this is a good moment to express some commitment. Of course, these things have to be said. They don't always materialize in changes in stances. But I think it has to be no regrets from us to try and make sure people understand what we bring to patients while we do it, what it means for countries and for Europe in particular. and be very composed with where Europe sits between the U.S. and China. It's delicate, as you would imagine. Okay, next question.

Yes, next question from Joe Walton from UBS.

Thank you. I've got one, I guess, slightly philosophical question about R&D and then one about situation in the U.S. So the philosophical one is, We've seen a couple of what look like failed results, or at least not particularly good results, which have been blamed on very small sizes of studies. So we can't get to increase our probabilities of success until perhaps the studies are bigger. Are there any other of your phase two studies that are coming out that we may also find just perhaps a little bit too small to give us the answer that we want? And I'm thinking the OX40 ligand, the data wasn't statistically significant. You're very convinced it's going to be competitive with Bimzelex, for example, in HS, but we can't see that data yet. And the oral TNF, that also seems to be too small a study to be really very clear about it. Could you perhaps tell us whether you think there is still a decent chance of an oral-only indication for something like RA, or whether this is really going to always now be perceived as a combination product. And my second question is just in the US. And Paul, I'm asking you this as your role in pharma more than from a Sanofi perspective. But if you do get the opportunity to renegotiate the IRA and go from nine to 13 years for everything, which everybody thinks appears to be what Trump is encouraging Congress to do, do you think there will be a significant pay away that you will have to give in exchange for that because clearly the CBO would say, well, that's going to cost us much more money. So should we see that still as a net benefit for the industry? Many thanks.

Okay. Thanks, Joe. One of the fastest to connect. Thank you.

Yeah. So Joe, thank you for the philosophical question. Let me be very direct. I've been very reflective about the comments we've received after disclosure of our results. In an effort to demonstrate an abundance of caution, in an effort to be extremely statistically rigorous, I think we may have not conveyed the clarity of the message about the value and success of these trials. And I'm just going to say this very directly. And you will see the data, but with the Amelie Asma data, we've been very clear that we missed the primary endpoint. But I've been abundantly clear that there is no equivocation in my mind that this is a drug. We'll go through phase three. And with a reasonable wind behind us, as with all phase threes, I have significant confidence that it will be successful. So this isn't a function of a small trial. There are always, in new exploratory-based finding studies, a bit of statistical wobble. But my confidence in ameliasmus is unequivocal. Secondly, in brevetamig, the study did not miss its primary endpoint. We went to some pains to craft a language about not missing its primary endpoint. Just to be super clear, the study's statistical approach was a Bayesian approach, which we didn't invent, actually. It's a Bayesian approach that is very similar to the first in human for Bimzelex, published by Sophie Glatt as the first author, and my old friend Steve Shaw as the final author. I was there when that study was delivered. So very straightforward, and I won't explain it here, Bayesian study. the credibility intervals on that molecule did not pass the null point. I won't talk about the exact numbers, but the level of confidence by which we know this is better than placebo, albeit in a super early study, it's not just compelling. It's not highly compelling. It's exquisitely highly compelling, right? So we didn't miss the primary endpoint, but we've been really very diligent about not making claims that we might be criticized for latency. And then the final question is on the small molecule TNFR1. We have to be humble in the case of disease. We tried this molecule in a disease that isn't exquisitely anti-TNF responsive. We did it because you can judge plazies on the skin very quickly. We needed to make sure the molecule was safe. We needed to make sure, as Paul has said, have a differentiated safety profile. We also needed to make sure that we could judge the dose appropriately. And skin is a very good way to assess dose response. I think that a disorder like rheumatoid arthritis that is more exquisitely TNF responsive may show a greater relative efficacy profile. But we said from the very beginning that as well as treatment in rheumatoid arthritis and other TNF responsive disorders, we would go into combination therapy, and I feel that the conversations with multiple large pharma partners who have significant provenance in this space is unequivocal, in my mind, validation of the value of this as a combination therapy federation and its source.

So philosophically, I think we're in good shape. Yeah, thank you. You know, it's a good question because you mentioned, you know, because we've had bigger populations. I think you touched on it. I don't want to repeat myself or repeat what you said too much, but it was about safety, at least, and showing some efficacy in psoriasis before we go into RA. I think back to the monotherapy question, it would be great to deliver a primary input NRA later in the year. But we'll wait and see because the safety meant that we're combinable. And that was always the subtext. I thought we'd been quite explicit, but we will see. There was efficacy. I've been in psoriasis for a very long time. The efficacy bar has already been set. There was really no way to ever achieve that, but our alternative was to really start with the RA study, and that would have taken too long. So I think perhaps we took some risk in terms of not delivering the primary input in psoriasis, but I think we sort of understood that. To be clear, we're pretty much at the end of the phase twos now in immunology. So in answer to the first part of your question, what else might we see or even miss on? I don't really think that's a question at this point. As for the pharma piece, you know, and I think Francois answered it very eloquently, you know, there's really scant detail in terms of the numbers to be able to make any type of predictions. However, the executive order from last week was reasonably explicit in its intensity. It stepped back a little bit from most favored nation, stepped forward a little bit into what it means for patients and what it could mean for out-of-pocket, and importantly brought in 340B and PBMs into that narrative. I would imagine will be a painful because you know clearly if you've moved from 9 to 13 there would be and we'd be delighted as an industry because I think some small molecule innovation was lost in that mistake first time round. I think it looks to me at least from the executive order and subsequent conversations that it may be a shared responsibility in how we get there to do that. I would hope that's the case. Again, with the administration, we take that into granted. We've read the executive order. We reflect on it, and we'll see what it means in practical application. Next question.

Yes. Next question from . Hi.

Can you hear me? Yeah. Great. So I just wanted to go back to the question on tariffs. and just sort of push Franco Xavier a little bit on that. So based on the administration comments, they have talked about 25% farmer tariffs in Section 232, and there's a lot of discussion around whether that goes on to transfer prices into the U.S. So perhaps you could just help us by, if that's the most likely scenario, what sort of impact could that have on Sanofi, a 25% tariff on transfer prices into the U.S.? ? How easily could you mitigate that either with prices at one end or with just lowering transfer prices and with that, is there a material impact on Sanofi tax rate? And also perhaps on depiction, just help us understand where the US supply is coming from. Is it all Regeneron, Ireland and US plants or is there a Sanofi impact from Sanofi's European plants as well? And then just following upon the question around being competitive, when you say competitive with existing assets, do you mean it's sort of same ballpark or are you looking for something here that is better than what's there already?

Thank you. Okay, thank you. I'm going to try to show what you are able to.

No, I wish I could help you, but once again, I mean, I don't want to start discussing about various scenarios because it's very speculative by nature. Once again, we are aware of some of the tariffs that are impacting, for example, trade between the U.S. and China, for example, which we have factored in fully in our confirmed guidance for the year 2025. After that, I don't want to enter into the scenario. We are talking about 25% because we could run scenarios at 5%, 10%, whatever it is, on which product that is applied to which country, from which country. Very, very difficult to comment on what is, once again, relatively speculative. As of now. Let me just help you a bit, though, on our industrial footprint in the U.S. So regarding our presence in production footprint in the U.S., Sanofi has been, even prior to the discussions about tariffs, actively increasing its share of manufacturing in the U.S., and specifically biological drug substance. So we continue to assess our future capacity requirements, and we are considering additional measures, potentially including investment in the U.S. aligning our industrial footprint to the needs of our pipeline and to our expected future goals. So just as we did, for example, our modulus investment in Europe and Asia, as we do as well as the modernization of our front court insulin site, we are always exploring opportunities to expand our industrial footprint, including in the U.S., to meet both our production needs and the needs of our patients. Thank you.

Thank you for the question, Graham. Let's just very briefly start with the caveats, which is, as I said to Joe, we explicitly fund use of caution. We don't over-interpret our small studies. We convey the messages very clearly to the outside world because I believe we've attained a level of credibility in R&D that we need to enviously protect. With that said, and the caveat that we used precedented statistical approach that, in fact, the McKissam app used, I think that this molecule has a chance to fall somewhere between the two bookends that you provided. And we will find out when we run it in a broader group of patients. I still think, by the way, that A, it's competitive, and the unmet medical need, as we found with psoriasis, with this extremely severe skin disorder, will continue to progress and emerge. And that's what we're hearing from all the conferences that have come up.

Okay, thank you. Next question, please.

Next question is from Florian from Bernstein.

Okay. We should perhaps move on.

Okay. Next question is from Jen Quigley from Goldman Sachs.

James, we've got two.

Excellent, thanks for taking my question. We've got two, please. So, first, I'm going to tell them I have an asthma. Apologies if I may have missed that. But you've highlighted your confidence in moving to Phase 3, given the potential benefits demonstrated. But would you be able to share if you're planning to move into Phase 3 with the broad population or a selected population or multiple Phase 3s across different populations? It would be good to get your thoughts there. And how quickly do you expect to move here? And what could be the next steps into starting the Phase 3? And secondly, on the gross margin, the impact is pretty strong this quarter with COGS declining slightly year-on-year versus the increase in revenue. So could you give us a little bit more color over the drivers of the gross margin? To what extent is it partly driven by some of the benefits from the new depiction manufacturing process? And how would you expect the gross margin to progress through the rest of 25 and into 26? Thank you.

James, the Heumann family.

Thanks for the question, James. The first point is that it's important to say we've just got this data. We've recently received the data, are in deep consultations with significant KOs in the space who, by the way, thus far seem excited by the data and will continue that work to define the Phase 3 protocol fully. We need to make sure the community is with us. But the short answer to your question is that we have unequivocally identified in our Phase 2 population with high unmet medical need, and we will ensure that that population is overrepresented in any phase three study we do.

Maybe I'll add a little bit to that because, of course, we have the benefit of seeing the data. We never want to risk any publications or anything like that. But the population, I think, is a significant percentage of the biologic eligibles, just to be clear. So that's very, very important for us. And I think people need to realize that, you know, when we originally went to take on the X40 ligand, it was targeted at AD originally. That was the original acquisition. Our base case in AD, not that anybody's asked, is that we meet the primary input. That is where we would like to be. And that's our base case. Of course, the science will tell us whether we are right or not. And asthma, the daily asthma is actually very encouraging in terms of safety and efficacy. So we'll wait and see. You know, this thing, you turn these cards over, but I think we feel very positive. Gross margin.

Yes, gross margin, James. If you look at it five years ago, we were significantly behind our peers in terms of gross margin, almost 5 percentage points. Today, we are almost at par with our peers in terms of average gross margin. You saw a significant increase in Q1, 2 percentage points. From last year, about a third of it is linked to inventory revaluation that happens traditionally up or down, but in that case it's up in Q1. But being that you have two-thirds of it is linked to essentially product mix and efficiencies. As you know, we have significantly worked in order to improve the efficiency of our industrial footprint over the last couple of years, and we are starting to get the benefits now. And the product mix is happening across the board. It's not only the pixels you were mentioning. The new depiction process, it is one factor. Among others, by the way, this one has been spread over a few years, so it's not specific to Q1. And it started already two years ago, and it's not completed yet. So it's over a relatively long period. Going forward, do we expect to see some further increase in gross margin? Not necessarily significant for the remainder of 2025, but over the next couple of years, we will continue to see a gross margin. Okay. Thank you. Next question.

Okay, let's try again with Florian Cespedes from Bernstein.

Good afternoon, Florian Cespedes from Bernstein. Can you hear me? Yes, we got you. Good, thank you very much for that. So two quick questions, please. First, I'd like to come back on amlitalimab. Could you maybe give a little bit more color on the percentage of the population with severe asthma that we should consider? respond the most to the product. You highlighted the as-in-a-field or neutral field. What percentage of Sifirazna population do these people represent? And my second question is on Medicare Part B redesign. It was supposed to impact most likely the, more heavily the first quarter and then the impact should ease during the course of the year. Could you maybe elaborate a bit and give some color on the impact from this measure on your accounts?

Thank you. Thank you, Jerome. In the interest of time, I'll just quickly answer the subpopulation question. We're not shared, and we're not trying to help calibrate that at the moment. We'll get into the phase three, and we can get into more detail on that. Brian Pugdy.

Yeah, Medicare Part D, remember there's two pieces to this. First piece, actually, I'll cover depictions a little bit more specifically. Just to remind you, most of our business, more than 70% of our business is still on the commercial side. About 30% of it is on the government-based side. A percentage of that is actually Medicare quite specifically. And then there's two pieces as it relates to the Medicare Part D redesign. One is obviously the covering the gap there, and that is we've seen a slight impact of that, obviously, as we anticipated, and that was part of our plans. Actually, we originally knew this for quite some time. But the other part that actually is interesting to us is the cap of $2,000 out-of-pocket. And while we haven't seen an inflection of that yet, there are some early signs that actually there might be more patients up for grabs now with the fact that they have no more than $2,000 out-of-pocket expense. So we'll see how that progresses in 2025. But so far, we think that there'll be some positives and some offset of that, actually, for the Medicare Part D redesign.

Okay. Thank you. Next question.

Next question is from Sarita Kapila from Morgan Stanley.

Hello. Can you hear me?

Yes, we got you.

Hi. Hi. Thank you for taking my question. Just a quick one on your US flu vaccine dynamics. I think you called out softer demand and intense buying pricing pressure. So is this baked into your guidance for this year? And consensus is factoring 3% sales growth for food this year. Should we be thinking about 25 as another year of potentially low single-digit declines? And then taking a step back on AD, you have multiple modalities, OX40, IRX, also Biospecifics with Lensicomig. Some of your peers, Pfizer and J&J, are pursuing tri-specific, so it would be interesting to get your thoughts here. Is this something you also plan to do? And any thoughts on tri-specifics and AD3 would be interesting. Thank you.

Okay. Thomas?

Yes, thank you, Sarita. On US flu, a bit too early to be definitive there because we're still in pre-booking period right now for flu in the US. But we wanted to highlight what we observe in this process. You remember that last year during the flu season, we observed in the U.S. a soft vaccination coverage rate, roughly minus 5% for the U.S. population last year, and that turns out to generate some price competition as we observe it today in the U.S. for the pre-booking. A bit too early. Usually, I give more color on the filter earnings after the pre-booking season, so stay tuned for the next part.

Thank you. Hooman, tri-specifics? Yeah, we're at close to time, so I'll be super brief. Just to say, obviously, we are well aware of tri-specifics. Our nanobody platform allows us to generate tri- or quadra-specifics, et cetera. It's an area we've looked at. Just a point of caution, it's very hard to calibrate the geometric interactions between each of the heads, and we don't expect repeated incremental additional value. We're adding additional But the short answer to your question is, yes, of course, we've thought about tri-specific. And I should say, when you talk about atopic dermatitis, I just want to remind everybody that it's a massively biologically under-penetrated marketplace, and there is substantial room for new molecules in that space. We remain committed to Dipson.

Yeah, and just before we get to the last question, I think this is – we said this at the end of, I think it was, 23th of D-Day. I think it's still not fully appreciated. diseases drive up biologic penetration. I think we're still at low double digit or high single digit. 14 in AD. 86% of the patients that are biologic eligible don't get a biologic in AD. So we know that RA is close to the 50% at this point. Between then and there, there is so much opportunity. And it's new entrants, different approaches. I think this coexisting of different mechanisms is completely different. underrepresented in forecasting. Still, we see people thinking it's winners and losers. A good example would be the enthusiasm we have, and you said it up top, for amlitalimab and dupixen to both grow very well all the way to the end of patent by taking a new patient and coexist with different approaches. And over time, people's confidence in this approach will play out. But for us, having seen a little bit more data than the rest of you, We're very confident in how that's happening. Okay, last question.

Yes, last question from Simon Baker from Redburn.

Thank you for taking out my question at the end. Most of them have been picked up, so I can be pretty quick. Firstly, just going back to brevacumab. You gave us the p-value human. I just wanted to give Mr. Bajan's study to give us the posterior probability in that study. And then moving back to the oral TNF, I'm thinking about the internal combination candidates the IVAC4 degrade has sprung to mind. Are there any others that we should be thinking about that you may want to combine the oral TNA with? Thanks so much.

Okay. Well, we'll finish on this over the end.

Repeat your second question briefly for me.

Combinations, other oral combinations, internal and external.

Yeah, okay. Thank you. OK, so Simon, thank you for asking the excellent Bayesian question. I can't give you the posterior probability, nor did I give you the probability unless I was hallucinating. Apparently, the probability is . So no, I can't give you the posterior probability. But actually, based on the data in the public domain in HS, you could work it out. That's a little test for you. And the answer for you, you'll appreciate that based on the data in the footnote, it's compelling. And then the answer to the convo is there are multiple rational combinations. It would be unwise of me to disclose and prior art myself in this discussion. But I think that the natural combinations with a TNF super clear to people in the arts, and we will pursue many of them.

Yeah, and maybe just to finish on that note, they're sort of obvious, I guess, based on whether you're trying to break new efficacy goals, could be an IBD, could be an RA, could be different methods to treat diseases. You know, I think the open question we asked ourselves some time ago was, where is TNF approved and indicated? Where was it overtaken? Non-injectable site, other. more selective approaches. And then if you're going into orals, what does that tell you about the combinations that would be ideal? Because either are likely to not make it on efficacy on their own, but together they would. And that's the magic. So we'll get into that over the coming months and hopefully have some things to share and we'll do that as we go. But otherwise, thank you all for the call. Appreciate it. And we look forward to catching up with you soon.