Sanofi (SAN) Earnings Call Transcript & Summary

Good evening, good morning, good afternoon, everyone, and thank you for joining us. My name is Keyur Parekh, and I cover Sanofi for Goldman Sachs. Dietmar, thank you so much for taking the time to join us in California. Unfortunately, I'm stuck in somewhat sunny London. So that's kind of the saving grace, but thank you again for making the trip. I appreciate it. Dietmar, before we kind of go to Q&A, just [indiscernible] of introduction for everybody listening in. Dietmar is the head of Global kind of Development and the Chief Medical Officer for Sanofi, having joined Sanofi about 2.5 years back. Dietmar, I don't know if you want to make some opening comments on kind of your 2.5 years at Sanofi, how that's kind of progressed, the kind of changes you've made, what you see -- what excites you today before we get into specific stuff.

Yes, Great. Thanks for having me, first of all, and this is a new format for me where you are interviewed from the screen. So I hope you can see me all right and hear me all right. Yes, I joined Sanofi roughly 3 years ago, actually already. And it's been a really good journey, right? I'm often speaking about the journey that we're taking with the company where we are moving from a company that was primarily focused on Primary Care, Diabetes, Cardiovascular, now to areas of much larger unmet medical needs to Immunology, to Oncology, Neurology. And what has really excited me about those last 3 years is -- I want to pick 2 things. One is definitely the portfolio where we made major changes [indiscernible] you've seen and I hope we can speak about some of that during this talk as well, where we've seen clear progress in Immunology with Dupixent, but also with the pipeline behind it, which I really think is an industry-leading portfolio in Immunology, then also in Oncology, in Neurology. Really the focus is on these novel medicines that I think will make a major difference for patients. And then the second component behind the portfolio is really the progress we're making also as an organization, right? For example, the development group has been entirely restructured. We're really focusing much more on deliverables. We're focusing much more on utilizing modern methods. We're focusing on how can we bring our medicines, our first-in-class and best-in-class medicines, which are now our focus to patients much faster. And again, I think we've made very good progress there also from an organizational and operational perspective. And that's also externally validated. When you look at the portfolio, the external validation is clearly there where the portfolio value has increased dramatically. We're now definitely a very meaningful portfolio of novel drugs, close to 90% are now in this first-in-class, best-in-class category, also from an external perspective. And then when we look at the organizational and operational progress, when we look at our CMR and KMR data, we're in the top quartile for delivery of Phase I, Phase II, Phase III studies, but also when it comes to efficiency of our development. So I'm quite proud of that journey, and it has been a good journey.

Excellent. Dietmar, there were a bunch of things you kind of touched upon, which I want to dig a bit kind of deeper into. And what I'm going to try and do is perhaps sort of split [indiscernible] into 2 parts. I'm going to start with some kind of broad questions kind of either for the Sanofi group or even interested in your thoughts kind of for the industry as a whole. And then go on to some specific assets that I'm kind of keen to talk about. So if we kind of start with the first one at a big picture level, what are some of those changes that have happened at Sanofi over the last 2.5 years? And how far in the journey of change do you think we are? So if you think about maybe 2 or 3 big changes that have happened in the R&D organization at Sanofi in the last 3, 6 months, what have they been?

It's -- I cannot say there's changes over the last 6 months, but definitely changes over the last 2.5 to 3 years, several of those. One is a real focus on bringing in anchor assets and platforms on the reserve side. Platforms that we can utilize broadly that we can utilize to target, biological targets that we understand and that we discover more broadly. And when you think about it now in the portfolio, we have modern antibody constructs, trispecifics, bispecifics. We have Nanobodies at our availability. We have the potential to use synthetic biology with Synthorins that came from Synthorx in San Diego. We are looking at small molecules as well. We're looking at immuno-oncology. We have this plethora really of technologies and platforms that allow us to, in a much faster fashion and in a much more targeted fashion, develop molecules for specific targets. More recently, we've also added cellular therapies as a key modality with our NK cell focus. We added antibody-drug conjugates. I'm just coming back from the ASCO meeting, the American Society of Clinical Oncology, where we clearly got the feedback, ADCs and NK cells are currently at the frontiers of what we want to do in oncology. So I feel really good about what we've achieved, positioning a very effective and developing a very effective research machine. Then on the development side, some of the key changes there are really around integration of the operational and the more strategic parts around how can we get too fast the decision-making? How can we bring our molecules to patients much faster? And we've made major changes there, both from a perspective of organizational structure. But also from a perspective of who are the leaders in the organization, who are the people who drive these types of developments, who are the therapeutic area heads, how do we make decisions? And you will see that, obviously, when you develop first-in-class and best-in-class medicines, you have to take more risk. So we'll see also in the portfolio that we're placing our bets very carefully, but we're not afraid of really interrogating the biology when we feel eventually it can lead to benefit for patients.

So as -- Dietmar, you mentioned ASCO and this is something that I want to kind of dig a bit deeper into, right? And perhaps provocatively, I think the industry is spending somewhere between $50 million, $60 million, $70 million a year kind of on oncology research at a minimum, kind of across the industry, not just Sanofi. I think the DESTINY-Breast04 study was a great outcome kind of for -- coming out of ASCO. But to me and to a lot of investors, we speak to, unfortunately, as the only late-stage clinical study where people saw a real change in standard of care. And I think that's kind of been a track record over the last few years where we've had a lot of money being spent on oncology R&D. And yet, trial results don't necessarily [ borne out ] kind of that when it comes to making meaningful changes to standard of care. Is that kind of an assessment you would agree with? Do you think that's a flawed perspective from an investor perspective? How do you think about oncology R&D?

Yes, we have to think about it in a differentiated way in my mind. When you look at the American Cancer Society on an annual basis, publishes a report as does ASCO and as do other organizations. When you look at long-term survival in oncology, we are currently curing about 2/3 of patients with a malignant disease. When you look a few years back, that was only about 50%. And that advance in treatment of patients, the longer survival times, the better treatment, the larger number of options that these patients have is really a function of all the research that we've done. So as I'm looking at the patient benefit on one side, but I do understand the sentiment that there's been a lot of investment. And what do you get for this investment? You can be on the positive side, where you look at the PD-1 space, and you've just very meaningful benefits also from a financial perspective and from a patient perspective. When you look at the big news that you have quoted from this ASCO, which is really in the ADC space. And we see a lot of development in ADCs and with [indiscernible] trastuzumab deruxtecan. We see really a reshaping of the treatment of breast cancer that I think will be very, very meaningful. So you have to place your bets carefully. That's the lesson that I take from that. And I'm looking at our own success rate, that's what I want to do. And I think you see -- and that's now across the portfolio, not only oncology, right? You see across the portfolio, actually very meaningful progress, right? We can speak more about Dupi and the different indications that we add successfully to the early indications that we had, whether it's [indiscernible], whether it's eosinophilic esophagitis. We are waiting for data on cold-induced urticaria. So we're seeing real progress on that side in immunology. We're also working on a broader portfolio behind that. When we look at hematology, we just presented very positive -- we've just seen very positive data with efanesoctocog alfa, and the data will be presented very soon. So that is a real game changer, in my mind, in hemophilia, positive data there. We also had other data sets in the Rare Disease space with olipudase with Nexviazyme that enabled registrations for patient populations in need. So we had quite a good series of successes more recently, and we had our share also of areas where we were not successful in the initial studies, but we're still thinking carefully about how to move the molecules forward and really learn from those studies and really eventually benefit also the broader space and our development. So I think overall, our return on investment at this point in time, I look at the more recent developments quite positively.

So how would you categorize your return on investments? Kind of do you think Sanofi R&D today is earning above cost of capital returns on your R&D investments? Do you think it's below cost of capital but getting towards above our cost of capital?

Well, I'm not the financial person, right? So I cannot comment on all of those details. But I see the recent readouts have been very positive for us. I also see that we have communicated broadly on business operating income and the goals that we have there and the return to the community, the financial community as well, and we're just going to stick with that, what we have presented during the recent quarter. And I think that picture when you look at the business success, when you look at the readouts that we had, when you look at really a tremendously successful quarter also from an R&D perspective, I think we are on the right track.

One of the things you mentioned, Dietmar, was this journey kind of from being an organization that was focused on Diabetes, Cardiovascular, Primary Care, [indiscernible] the specialty-focused kind of medicines company. How far along the journey do you think Sanofi is today? And what do you think will give us or what are you looking at as the next markets to quantify progress on that journey?

So that, in my mind, is a differentiated picture. When you look at the immunology portfolio, and I already spoke about that, I think we absolutely have an industry-leading portfolio at this time in immunology. And when you look back 5 years, we literally had one molecule, right? Now we have a suite of molecules. You've seen at our recent Immunology Day, how this is coming together between the different molecules with Dupixent, amlitelimab, rilzabrutinib, itepekimab, then the nanobody portfolios to have a meaningful number of molecules that has the potential to change standard of care. And the beauty of immunology is obviously that all immunology is connected. So you're not talking about the small, small segments of patients, you're talking about opportunities that you see, for example, across the type 2 inflammation space with Dupixent or across the type 2 and type 17 and type 22 space with the OX40-Ligand antibody with amlitelimab. So I think that journey in immunology has been highly successful and really looking forward to the further development in that area. Then there are other spaces. Let's say, neurology. We have been in neurology for quite some time, but we had a portfolio that is nearing loss of [ exclusivity ]. And we have really thought about how can we come to the next generation of molecules in those spaces, for example, in Multiple Sclerosis. That's where, for example, tolebrutinib comes in. Tolebrutinib as a brain-penetrant BTK inhibitor is being developed broadly in Multiple Sclerosis and has the potential to change really the outcome of the disease for patients with relapsing/remitting MS but also primary progressive and secondary progressive. And we currently have it in [ 4 ] large Phase III studies, really broadly, global Phase III studies. So again, I think that journey is progressing nicely. Are we looking at additional opportunities in neurology? Yes, of course, we want to further supplement the portfolio. When we think about the Rare Disease and Rare Hematology space, again, I see us on a very, very good track. We had individual molecules and a rather classic portfolio a few years ago. You look at the portfolio now, we have recent successes very clearly in the Rare Disease space with olipudase, with Nexviazyme. And in the rare blood disorders in the hematology space, we had efanesoctocog that, in my mind, is a best-in-class Factor VIII -- elongated half-life Factor VIII that is without an alternative in the Factor VIII space. In the nonfactor market, you have fitusiran where we have presented data at the recent ASH meeting. And again, with 6 injections per year, you can potentially have an entirely new option for patients -- for those patients specifically that look for good protection with a convenient dosing schedule. So I think that journey in hematology is also going very well. And we have really a good dozen of molecules in the clinical portfolio in hematology and Rare Diseases at this point, right? And then that brings us to oncology. We have always spoken about the portfolio is actually in 3 different buckets. We have a late-stage portfolio with the likes of Sarclisa, tusamitamab ravtansine and amcenestrant in large areas of unmet medical need in myeloma with Sarclisa, in breast cancer with amcenestrant and in a broad range of solid tumor types that are CEACAM5-expressing with tusamitamab ravtansine. And those are late-stage molecules, which have a very defined development plan at this point and clear upside and very good opportunity. Then you've got a mid-stage portfolio that is in development. We have molecules like SAR'245, and that's our non-alpha IL-2. And then you have an earlier-stage portfolio that we're usually not speaking a lot about, but this is where the research portfolio comes in. This is where the more modern approaches come in. This is also where we have further ADC developments where we have NK cells as a therapeutic modality where we have our trispecific and bispecific portfolio, and we're just evaluating mechanisms also broadly across immuno-oncology and molecular oncology. That, I think, will take a little longer to come into -- to come to fruition, but we have this frontrunner molecules that actually have the near-term opportunities for us.

So if you put all of these things together, Dietmar, kind of what do you think the shape of the R&D spend at Sanofi looks like over the next few years?

But the shape of the R&D spend points upwards, right? That's really the confirmation that I can give you. We can also broadly -- we have also broadly communicated about that, right? We have a stronger focus on R&D. We want to invest more into R&D. We've not given this as a percentage of sales. We have said we are really spending more in R&D and substantially more. I can confirm from a development perspective, that's absolutely the case because the majority of that investment is coming to development, but there's also clearly substantial investment going into research, and you will see that in the portfolio, but that's -- that will increase, and we've committed to that increase over the next few years.

So should -- I mean, the way you're talking about this almost makes me think we're going to see a double-digit increase in absolute R&D spend kind of each year over the next few years. Is that a realistic outcome from your perspective?

I think it's a realistic projection that we will see an absolute increase in R&D spend over the next few years.

And kind of I am going to now move to some of the specific kind of assets, talk to kind of some of the things you mentioned about -- why don't we start with BIVV001, which you're clearly very excited about. You've kind of called it the best-in-class, long-acting Factor VIII molecule. We are going to see Phase III data in kind of 4 weeks' time at ISTH. What should we be looking out for? What do you think is going to make this a best-in-class molecule?

Yes. So the -- we call it efanesoctocog alfa at this point, right? The BIVV001 came from the Bioverativ acquisition exactly. It's a very elegantly designed molecule. It's a half-life elongated Factor VIII molecule, where really the positioning is that you can give it on a weekly basis. Many of the current Factor VIII have to be given every 2 days, every 3 days. But it's important to understand that what we're doing with the molecule is pretty much normalized Factor VIII levels for the majority of the week. So this is for patients who are more active, for patients who want to lead a normal life because they get this strong protection from bleeds. So when you look at the data, look at what's the annualized bleeding rate, which I think is very strong data, but also, how does that translate into clinical benefit, right? Because what we want to see is we want to see patients be active without the threat of joint bleeds, for example. Those are the debilitating events that these patients go through, right? And be aware that at this point in time, roughly 60% of the hemophilia patients still one way or the other use factor, right? They either use factor as their standard prophylaxis or they use factor in an on-demand fashion. So we're having a molecule that is clearly best-in-class for 2 reasons because of the application schedule and because of the stronger protection that you get. And we believe this is not only a molecule that will be used in this factor space. We believe this is a molecule that can also take back share from the nonfactor space because of its unique properties.

So obviously, kind of you've seen a lot of innovation, after multiple years of a lot of innovation in kind of hemophilia, we've seen first, Hemlibra and then kind of potentially gene therapy entering at some point of time, you're seeing your kind of asset, we will likely see incremental data from fitusiran [indiscernible], kind of other [indiscernible] over the next few years. How crowded do you think this market becomes -- and as you think about BIVV001 over the next kind of 3 to 5 years, do you still see this as being a differentiated asset kind of when you look at the competitive space around it?

I absolutely see it as a differentiated asset, yes. When you go to these hemophilia conferences, right? I'm a hematologist, oncologist by training, you will see that -- you will see patients there. You will see parents there. You will see people who absolutely want to own their own therapy. And with our offering, with our hematology portfolio, we're really trying to address the needs of the broad hemophilia patient population. So we have those patients that want to lead an active life, want to use a factor because that's really replacing the normal kind of situation in the body of these patients and patients who are fine with a weekly IV injection, right? So those are the patients for efanesoctocog, and I don't see anything on the horizon of current hemophilia development that could actually [indiscernible] characteristics. So I think it's a very differentiated molecule there. Then you've got people that are looking for convenience. Those are usually people who are currently on nonfactor therapies. That's your classic Hemlibra population. Those are patients that prefer a subcutaneous injection. With Hemlibra, usually, you give subcutaneous injections on a weekly or every other week. You can also go out to 4 weeks, but then really your efficacy is going down, look at the annualized bleeding rates. That's in my mind where the fitusiran data come in. We have presented some of that data at the recent ASH meeting. And there with -- we have the vision that within every other month injection, which with pretty much 6 injections per year, you would get effective protection. This is also what the data that we've presented so far actually indicate, you would get effective protection from bleeds with an easy subcutaneous every 8-week injection, and this is a thermostable formulation, so you can actually use it broadly really around the globe, and that's clearly a differentiated molecule and has the potential to be a best-in-class molecule also in this nonfactor space. And then there's a third space, which I think we will develop over time, which is the gene therapy space. Personally, I believe we need to look into nonviral gene therapies. I think that's the longer-term vision we need to have. We are working on nonviral gene therapies. I think they have clear advantages over lenti or adenovirus-based therapies, but that's more out in the future. I think in the midterm, you will be focusing on the factor and the nonfactor market here.

Now kind of change in topic, Dietmar, you spoke about CEACAM5, you kind of recently presented data on that. I think kind of the broad speed reaction was it's okay, kind of not really that great. So tell us why we are wrong on our interpretation of that data.

So tusamitamab ravtansine, our CEACAM5 ADC. I think it's a really interesting molecule, right? Various people have tried to target CEA or the carcinoembryonic antigen or the broader [ CEACAM ], like the associated target space. CEACAM5 is pretty unique and that it's uniquely expressed on tumor cells and not as much on normal cells. That's different with other types of [ CEACAM ] or CEA itself, right? So having an effective antibody against CEACAM5 is, in my mind, a unique opportunity. The data that we have just presented at ASCO are data from our initial study in the second-line non-squamous non-small cell lung cancer setting. What you usually see in these patients is that they get a therapy, they respond, but they also relapse quite quickly. This is a space that is, in my mind, a high unmet medical need. It's a space where you are post checkpoint inhibitor and chemotherapy. So even FDA has clearly voiced this is a space where currently we don't know what to offer these patients. So having an effective therapy in this space versus, for example, the [ classic docetaxel ] is, I think, a clear step forward. What we've shown at ASCO is long-term survival in those patients that respond, which is -- which you classically don't see that. That's where -- when we spoke to key opinion leaders, when we spoke to [ treaters ], in the space, they were really excited about this data. Yes, it's a smaller patient population. Obviously, we're looking at the CEACAM5 high patients. We're looking at the biomarker-defined population, but it's just a really good proof of principle. We are evaluating CEACAM5 more broadly, tusamitamab ravtansine more broadly, also in other tumor types in gastric cancer, breast, pancreatic, other types of tumors. We're also looking at how can we bring it earlier in the treatment paradigm because that's where the key opportunity lies. And that's we are looking forward to see data from the first-line setting. That study is currently ongoing, CARMEN-LC05. We will see data from this study also during the second half of the year. And then that will enable us to think about how do you approach the first-line space. We think you can maximize benefit from CEACAM5 targeting in the first-line space. We don't know exactly how that will look, right? We don't know do you combine with chemo and a checkpoint inhibitor, could you eventually even propose like a chemo-free option with just a checkpoint inhibitor and an antibody-drug conjugate? That is the data that will come out of our LC05 study that will really tell us how can you get into that earlier space. And then beyond that, we're also working on what's actually the right toxin? Because in non-small cell lung cancer, we think the current toxin works well. There are other CEACAM5-positive tumors where you do not want the maytansinoid-based, like a vinca or taxane like toxin, where you actually want something that's more like a [ topoisomerase ] inhibitor. And we're actually working on that and really broadening also the approach, how can we target CEACAM5. That's a longer answer, but I hope it shows you that I'm actually quite excited about targeting CEACAM5.

Yes, it does, indeed. Moving on to amcenestrant. And obviously, we saw -- we have kind of [indiscernible]. What gives -- obviously, you've seen the [indiscernible] kind of headline data as well. And why is the industry still so bullish about kind of oral SERDs? And why are they so optimistic kind of for the use in the earlier lines of treatment?

I think everybody is so bullish because there's just a large unmet need that we think we can address right? We know that hormone receptor-positive breast cancer is driven by estrogen. Some of them also by progesterone, but largely by estrogen. So we know if we take the receptor out that we can impact progression of these tumors that has been shown very convincingly with tools that we feel are not optimal with estrogen receptor modulators like tamoxifen with aromatase inhibitors and also with earlier SERDs like fulvestrant, that are really cumbersome to give if you have an intramuscular injection every 2 weeks, it's just painful and cumbersome, right? That's as to why fulvestrant is not used in the adjuvant setting. That's where we think having a new backbone, a new backbone hormonal therapy actually makes eminent sense. What do you need to see for that to be successful? You need to see good degradation of the estrogen receptor. We've just been at ASCO, demonstrating in our window study, in our AMEERA-4 study that we see very good degradation of the estrogen receptor even after 2 weeks of treatment and that we see really good down regulation of Ki-67, which is a proliferation marker. So we see the drug is clearly effective. We've also seen this in our Phase I studies. And eventually, once you see the AMEERA-3 data, you will also see that our drug is clearly effective. It just in AMEERA-3 wasn't better than the [indiscernible] that is fulvestrant, right? It was not statistically significantly better. And that's what we were trying to do in AMEERA-3. But as you move it forward into earlier lines of therapy, you're now comparing it to an aromatase inhibitor and you're moving into spaces where the current SERDs like fulvestrant cannot even go. And that's where the huge opportunity is. That's where our AMEERA-6 study comes in, which is a study in the post aromatase inhibitor adjuvant setting, and we feel there the [indiscernible] is tamoxifen and we feel that we have a really good opportunity to win in that space. We also think, as you move earlier in the treatment paradigm, tumors are more hormone sensitive, right? If you look at AMEERA-3, that's in a largely hormone-resistant space, right, where it's difficult to demonstrate their difference. But as you move earlier, you get into these more hormone-sensitive tumor types, and we feel that tolerability is key. And amcenestrant is a molecule that is highly effective, but also eminently tolerable. And that's where we feel the differentiation will come in, and that's why we are absolutely continuing to pursue our amcenestrant program.

So 2 questions on the back of that. The first one, when do we see AMEERA-3? And then secondly, have you made any changes to any of the ongoing studies based on AMEERA-3 data that you have in-house?

So you will see AMEERA-3 at a conference later during the year, this year. And we have not made any changes to our program. We're actually talking about how do we think more broadly than about application of amcenestrant both in the first-line space and in the adjuvant space. We have not made changes to the current program. We're actually more thinking about how can we add to the program moving forward? Because you have seen that there are changes in the broader treatment space in hormone receptor-positive breast cancer, you've seen different data also at ASCO with regards to which CDK4/6 inhibitor to use, which other drugs potentially to combine with. So our thinking goes more along those lines, but we've not made any changes to our current studies.

Dietmar, kind of moving therapy areas, kind of focusing, moving to kind of tolebrutinib, clearly something you guys are very excited about. You've kind of thought of it as being the best-in-class kind of brain-penetrant BTKi. Can you just remind us the relevance of that from a clinical perspective and what gives you the confidence that in 3 years' time when all the Phase III studies have read out, there will be clinical differentiation between the BTK inhibitor class in MS?

Yes. We're convinced that in MS, it's important to address both innate and adaptive immunity and then to get the drug also into the brain. We feel that's important because even if you inhibit B-cells, for example, circulating B-cells, you still see progression of the disease. And when you think about that progression, most likely the microglia, the glial cells in the brain play a key role. And those cells also use BTK as a mechanism. So we feel with BTK inhibition, you can address the peripheral B-cells, you can address the central B-cells, you can address the microglia cells, and you need to get enough drug into the CNS, right, into the cerebrospinal fluid that you can actually have activity at those levels. At ECTRIMS, we've demonstrated data for tolebrutinib, which really is the only published data for a BTK inhibitor that you get levels into the brain and into the CSF that actually inhibit microglial cells. So we think it's a differentiated molecule based on brain penetration, based on activity centrally and peripherally. We have seen really good Phase II data, the Phase III program with [ 4 ] studies, is going on very nicely, and we're really looking forward to see data in the, relapsing/remitting space. Then enabling a filing in 2024 and then see data in the progressive space to enable filing a year later.

Dietmar, I'm conscious of time, and I know we're kind of running into the last few minutes of this chat. So I'm going to ask my colleague [indiscernible] to come join you on the stage so he can help kind of moderate any audience kind of questions live in the room.

Sure. So we are opening straight up for Q&A. Is there any questions out there? [indiscernible] it straightaway. So maybe one for me on capital allocation. So -- you've spoken sort of more broadly about your desire to be the leading immunology company, and you run us through [indiscernible] pipeline earlier. Is this an area that you'd be looking to add [indiscernible]?

Well, we're constantly looking at also external opportunities, right? We have a really good research effort ongoing in immunology, but also in oncology and other areas. But there's a lot of external really interesting work ongoing, and we're constantly looking how can we complement the portfolio? And when you look at some of our recent acquisitions, right, some of those were also in immunology and they've clearly added to the portfolio. And let me just highlight amlitelimab, rilzabrutinib have been coming from external acquisitions and form key parts of our current portfolio in immunology.

Dietmar, if you kind of take that immunologic [indiscernible] obviously, one of the big investment debates kind of out there is what is in your pipeline beyond Dupixent. You've got a great franchise in Dupixent, you've got additional indications coming. But as we look at beyond Dupixent, can you talk to maybe a couple of assets that give you the confidence that you have the depth and the breadth of internal pipeline in immunology?

Yes. Yes, absolutely, right. And we've spoken about some of those already. So first of all, Dupixent, you will see more indications, as you've seen more recently, you will see regional expansion, you will see additional age groups. That's where the growth for Dupixent comes in. And that does not even include in the current projections, what we're doing in COPD, right? So there's definitely more to come for Dupixent and really a lot more opportunity. Then I want to highlight itepekimab, that's our anti-IL-33 antibody. Good Phase II data in COPD, very interesting. I think we've uncovered a new biology there. In that, obviously, IL-33 seems to play a role in those prior smokers -- in the prior smoker population. Remember, we had a Phase II study that was looking more broadly in the prior smoker population, which is 75% of our COPD patients, we saw a 42% reduction in exacerbations. Unprecedented, and we think a really important unmet need and a good opportunity to bring a biologic then to the COPD space. So watch out for those data. Those studies are going on, and those will hopefully read out in 2024. That's what we have communicated at this time. Then rilzabrutinib came to us through the Principia acquisition. Strong data in ITP, in Immune thrombocytopenia, giving us proof of concept in autoantibody-mediated diseases, but we believe BTK is playing a broader role not only in autoantibody generation but also in more allergy-type reactions via the Fc epsilon receptor, and that's where really the approach comes in where we're testing rilzabrutinib in atopic dermatitis, in asthma, in IgG4-related disease. So we're trying to see is there a broader space also in chronic spontaneous urticaria. Amlitelimab, our OX40-Ligand antibody, we believe is highly differentiated because we're targeting the ligand and not the receptor, which we feel is a key differentiation from a biology perspective. We also feel it's important that this is a nondepleting antibody versus depleting antibodies, which actually kill the OX40-expressing cells, for example, regulatory T cells. So we want to modify the immune response, want to actually modify the autoimmune phenomena going on, but without, for example, killing regulatory T cells, which are immunosuppressive. And when you look at our data, we do not see fever, pyrexia autoimmune phenomena, which you actually do see when you target OX40, right? And when you have a depleting antibody like our competitors. And then finally, last year, in 2021, we brought 5 Nanobodies into the clinic. So 5 combination molecules targeting different immunological targets. Those are coming out of our Ablynx collaboration, and those are currently in single and multi-ascending dose studies. So we need to move those forward. They're currently in early development, but they present major opportunities across the spectrum of immunological diseases, whether it's really in respiratory, but then also in GI, inflammatory bowel disease, also in the classic TNF-alpha indications. So we have a broad spectrum really of molecules that we're developing there.

Dietmar, thank you very much. I know we're running out of time. So your [ classic ] kind of [indiscernible] kind of question. One study you're looking out for in the next kind of 12 months that we should all -- that, one, you're excited about, but also one, we should be focusing on?

Sorry, you were hard to hear. Over the next 6 months or over in...?

Yes, next 6 months.

So what you'll see over the next 6 months is you're going to see the IMROZ readout for Sarclisa, which, in my mind, is a study we want to look for because it will tell us really is Sarclisa a best-in-class molecule? This is in the first-line transplant in eligible myeloma population. We've already seen very good data in later lines. So we think that's an important study. We also will see the Dupixent -- cold-induced urticaria during the second half of the year. And then you will see some really meaningful other studies coming in the '23 and '24 time frame. That's why you're looking forward, for example, for COPD data. That's why you're looking forward to tolebrutinib data. That's where you also will see some of the fitusiran, the amlitelimab. So really some data that, again, can be quite transformative for patients but also for us at Sanofi.

Dietmar, with that, thank you very much for your time and talk. We really appreciate it, and I hope you enjoy the rest of the day in sunny California.

Thank you.