Paul Hudson: Maybe I could add as well, Olivier, that we said it, we knew full well when we made the transaction. There’s a reason why some of these small companies sell a great medicine is because they just can’t do this type of work over this many years. If I could add anything, the quarterly transitions are less — of less interest at the moment, the screening numbers are where we’re heading. And we will, in 2026, 2027, 2028, this medicine is going to be a big deal contributing to the company would do the hard yards. And I’m not sure you mentioned, Olivier, but there was no competition for a decade. So we don’t need to rush this. We can do this properly. In fact, we’re the next competitor with the CD40 ligand. So in time invested in building proper screening, infusion capacity where necessary, doing these things.
We’ve all been on this journey before, I was with hep C., it was only with Remicade. You just do the work properly, and we’ll get the benefits a few years from now because there’s nothing to displace us. And that, of course, will set us up in the community for the CD40 ligand. So we’re actually really pleased with how guidelines and other things are falling quickly into that. Next question.
Operator: Yes. Next question from Seamus Fernandez from Guggenheim. Seamus?
Seamus Fernandez: Great. Thanks so much for the question. So I just wanted to clarify the tolerability comments around rilzabrutinib. Just to confirm, it says safety consistent with prior results on the slide. Just wanted to confirm that, that is consistent with the lack of an LFT or liver signal, as previously stated, as well as maybe confirmation to some degree that the MS population that the BTK signal and the MS population may actually be population-specific? And just a quick second question. Paul, just wanted to get a sense for how you’re thinking about business development from here. I guess, with the incremental investment in R&D, and the robust kind of pipeline dynamics heading forward. I wanted to get a better sense of how you’re thinking about business development going forward in terms of the perhaps areas that you’re most focused on building out or if there is a profitability or stage of development later stage that’s more interesting versus early stage?
Thanks so much.
Paul Hudson: Okay. Thank you, Seamus. Houman, tolerability; and some also comments about MS and the populations different responses.
Houman Ashrafian: Yeah. So Seamus, thanks for the question, both thoughtful. The first one brief and to the point, I can confirm that we are pleased with liver tolerability profile of rilzabrutinib thus far and are confident taking it forward. As you said, 0.2 on tolebrutinib, you very thoughtfully have called out the fact that multiple sclerosis appears to be a distinct indication with the BTKIs. There may be interaction between the BTKI and the underlying biology in MS, which pretty set people to let me signal, I think that’s, as you were referring to, reasonable hypothesis, we have data supporting it and reflects clinical experience. I think both of these points are recently are well made.
Paul Hudson: Thank you. On the BD, I guess, to M&A point, we guided to the sort of €2 billion to €5 billion range in bolt-ons, that’s sort of standard, I think. We did commit after Q3 last year that we would hold R&D through 2024 and 2025 round about €7.7 billion. So we don’t want to regale away from that. I don’t think that’s appropriate. Of course, we will get some failures in there, which will free up some capacity or some delayed starts or different things, which will mean that capacity will open up for us perhaps into 2025 and 2026. And then, of course, most of the big studies start to graduate as the pipeline comes along and that gives us the sort of automatic bandwidth. I think to maintain that, you might see more of our effort and energy on the bolt-ons, either in the early phases where this bigger spend comes later and we can absorb that without missing a commitment or indeed in the late stages where the R&D commitment ongoing is minimal, and we can hold the line on what we’ve said and perhaps bring in a later-stage asset.
We have a good balance sheet. We have to leverage that. But I think the discipline around working within the envelope on our R&D budget is to be maintained. Should I throw the normal CEO disclaimer in, we remain opportunistic and everything else. Of course, but we’ve given guidance to you, we’d like to honor it for us and for you and make sure we get it done. And if we find some opportunities to reallocate, that’s perhaps our biggest thing we’ll take it. But demonstrating the discipline post Q3 last year is the number one priority because don’t forget we’re having enough assets in-house to, we believe, to grow EPS, of course, and to do what we need to do and to go all the way through the LOE of Dupixent whenever that comes. But the discipline is what will be judged on, I think, over the next couple of years at least.
So that’s as much as I can share with you. Next question.
Operator: Yeah. Next question from Jo Walton from UBS. Jo?
Jo Walton: Yes. Can you hear me?
Paul Hudson: Yes.
Jo Walton: Excellent. Two quick questions then, please. On ALTUVIIIO, I wonder, is there any evidence of moderate patients rather than severe patients beginning to try prophylaxis given that this is now an ability to get to a normal level of factor clotting on Beyfortus, could you give us an idea of what the next countries would be? So you’ve obviously got potentially more demand than supply. What’s the sort of order of countries that we should be thinking of as you roll out because you said you would be rolling out some more this year? If I can just finally say, is there any read across from the failure in frexelimab in any of the other indications or should we see that as completely isolated?
Paul Hudson: Okay. Good, Jo. Good questions. Brian, ALTUVIIIO use moving into moderate?
Brian Foard: Yeah. I think I mean the way we think about the marketplace is actually, again, all these patients are on therapies. So it’s — when we talk about the switches, again, these patients are identified really early in their life and then they’re on some type of therapy. So from a moderate standpoint, we don’t think about it that way. Actually, we think about it as what type of therapy are you on? And what types of efficacy levels are you looking for or convenience levels are you looking for? And that’s why, again, we’re really bullish because of what we’ve seen from a switch standpoint the marketplace is really responding to the profile that we’re bringing, which is better efficacy near normal factor levels over a weekly period with a 1 dose type of therapy. So we’re seeing switches of all patient types, no matter the types of therapy that they’re on.
Paul Hudson: Thank you. I do think ALTUVIIIO is going to surprise everybody. I have to say all the feedback and a bit in the conferences, I think that near normal thing Jo mentioned is the goal. Thomas, I’m not sure whether you’re prepared to share a list of countries in what order, but maybe you could give some regional input?
Thomas Triomphe: Yes. And I can say a little bit of flavor of how we are doing it and why we’re not seeing so much more. So rightfully, as you said, Jo, of course, we are going to make sure that we have ample supply for the three geographies where we had significant uptake last year. You know very well about Spain, the U.S. and France. Moving forward, we’ve already during South Hemisphere season, Chile and a couple of regions in Australia. Moving forward for Northern Hemisphere 2024, I expect more European countries to pick up. What happens, and that’s very important to remember, each time we introduce a new immunization, it’s always — there is always a very specific national process for first setting up the right recommendations through the recommending body, then high setup and then we launch into the right national immunization schedule, which is why I cannot give you specific European countries right now because I need to leave it to the recommending bodies to make sure that we have those votes and we proceed for NS 2024.
In addition to this geography in Europe, very well, but we just got the registration of Beyfortus in Japan in Q1 2024. And you should expect a little bit of Japan and China sales in the private setup, I would say, not national immunization program for 2024 in order to prepare for larger volumes in the coming years, that’s for the following season.
Paul Hudson: Houman, I think Jo’s comment on rilzabrutinib is well-placed. So over to you.
Houman Ashrafian: Yeah. Thanks, Paul. Thanks, Jo. Great question. Just to be super clear, we’ve always positioned frexelimab, primarily on MS and T1D medication, and it’s clearly demonstrated as chops in MS in great detail and is progressing in T1D. It is incumbent on us as a patient-centric organization for us to be thoughtful about the broadest possible patient benefit we can bring with our drugs. In my own clinical practice, I treated a bunch of patients with Sjögren, and they are definitely an unmet medical need. We initiated some experimental medicine study to see whether we could signal seek in those indications. I don’t see the Sjögren’s readout as anything other than failure in a signal-seeking study, and we remain confident about frexelimab in the bigger latter indications.
Paul Hudson: Yes. I think you’re right, the type 1 diabetes and MS, where I think you said it already, but just the risk of repeating it. Where we have a pipeline in a product, we will go and explore some adjacent areas where we think there’s some pathway or some biological reason why there might be an impact. And you should expect more of that from us in like early pox, left and right the pipeline on the product drugs because we need to do that. I think we really need to do that. And of course, everybody’s tried Sjögren’s, because it’s difficult to crack. And we can’t go any bunches in we can do something. Okay. Next question?
Operator: Next question from David Risinger from Leerink. David?
David Risinger: Yes. Thanks very much and thanks for all the updates today. So I just have one question, and maybe you could comment in some detail, please? So the company has accelerating I&I Phase II readouts in 2025. Could you discuss the key cards that will be turning over for the candidates with the biggest commercial potential? Thanks very much.
Paul Hudson: Okay, David, thank you. So I think Houman will start with you on — we’ve already put them into two buckets, frankly. So we — I don’t know how much more we need to add. But for the readouts that you’re excited about, for example, Houman for I&I for 2025, specifically is what you asked.
Houman Ashrafian: Yeah, specifically. It’s like choosing between one’s favorite children for our readouts in 2025, but I’ll give it a go. So firstly, it’s our big letter. I mean you asked for the answers in some detail, and I will try and provide them with thoughtful detail. So our Phase IIs reading out, as you’ve seen there, amilitelimab in a variety of disorders, particularly and alopecia. Number one, as I said, with a nondepleting OX40 ligand inhibitor, we hit the type 2 inflammation, but also take on a bunch of other mechanisms. OX40 is often regarded to the checkpoint and a new checkpoint. And I’m excited about it’s alopecia areata and the [indiscernible], which have very diverse chemical indications. Obviously, we have an all RIPK1 with a role in ulcerative colitis.
We think that’s interesting. The biology is well-precedented. So number one, I think the amilitelimab constellation of therapeutic opportunities is interesting. I think the IRC degrader is super interesting. It’s mechanistically unique where we our partner have played both in atopic dermatitis as an oral therapy, but also in hidradenitis suppurativa again. And then two others, just to call out, as you asked what our favorites were. The oral TNFR1 signaling inhibitor has the potential to be a truly disruptive therapy for patients with inflammatory disease as it will capture potentially the value of classical TNF treatment but with a differentiated side effect profile not affecting TNFR2. And the second one I wanted to call out is, obviously, Lunsekimig, our very special molecule in asthma.
The reason it’s special is because it seeks to augment durability but also raise efficacy healing. And the way it does so is to take two modular targets, both of which are precedented mechanisms in asthma put them together. So what we do is learn from the ecosystem and with the excellence of our platforms to enhance what we know from the ecosystem. Before I jump off the pedestal, I also want to talk about Tomar [ph], because it would be remiss of me to talk about our pharma agents and not talk about the RSV products that are reading out in Phase II next year. We remain as excited about vaccines as we do as our pharma products.
Paul Hudson: So Houman, it’s nice it took you a while to David’s question — did you mention OX40 ligand in HS?
Houman Ashrafian: I didn’t mention, nor did I mention TL1A or some of the other…
Paul Hudson: TL1A will be up there, too. So it’s going to be busy. It’s going to be busy, but this is what we’ve been trying to get the company to this point. We don’t know if they will work, of course, but we do know that we would rather have the readouts. Okay. Next question?
Operator: The next question from Gary Steventon from Exane.
Gary Steventon: Hi. Thanks for taking the question. I hope you can hear me. Just firstly, on the outlook. Given the top line momentum, could you frame maybe the level of flexibility you have in the R&D and launch plan and hence, the likelihood that any outperformance could drop through to earnings? I mean, it wasn’t that long ago, you outlined the acceleration. So I assume that any near-term investment opportunities that you wanted to accelerate you perhaps have done already? And then secondly, just on the theme of the consumer separation, perhaps, François, it’s your first earnings call as CFO, I ask your thoughts on what might be on your list in the scenario where Sanofi was to receive a significant cash inflow. So really just your thoughts on appetite for larger volume or larger value of M&A, larger buybacks or willingness to operate with net cash for a period of time? Thank you.
