Thomas Triomphe: It’s an important question, Richard. And I would say the continuation of what we have observed over the past two years. The situation in the flu market overall is that there is definitely ample supply versus the demand. And that’s been accelerated by the decrease in flu VCR over the past couple of years, especially in North America for various reasons. I think one point to have in mind though is that it’s very linked to the fact that there has been very moderate flu season in terms of disease. And as you know very well, this year gets softer after three or four seasons that are lower and suddenly this year comes back after the first big hit. I’m saying that because right now, we’re in Western Europe with an increase of flu disease, and the US will not be immune to that.
But so that’s for the overall situation. Of course, we had anticipated that. That’s why we came earlier with differentiated flu vaccines. We have the two differentiated flu vaccines in our portfolio that have significant data — significant data that are showing impact in terms of improved protection versus infection compared to standard dose, which none of the competitors have. That’s what we call protection beyond flu. And that has brought the success of this differentiated vaccine, but represents still in H2 2023 more than 60% of our flu sales. So to summarize, I would say overall for standard dose price pressure in my expectation you’re correct. But we’re seeing still ample room for trajectory of differentiated flu vaccines such as [Zydus] (ph), Efluelda or [indiscernible].
Paul Hudson: Okay. Thank you. The next question, please.
Eva Schaefer-Jansen: The next question is from Graham Parry, Bank of America.
Graham Parry: Great. Thanks for taking my questions. So first question is just on ALTUVIIIO. I think you had quite a lot of patients on free drug in second or third quarter. Just if you could give us an update on how many patients are actually on free drug or bridging programs in Q4? And then how you’d expect that to progress into 2024? And then separately on the excuse me, on the Inhibrx asset, I recall Inhibrx had indicated that the FDA wanted some data linking functional AAT levels going to normal levels with some sort of clinical outcome, as a sort of precursor to filing on the basis of, functional AAT level for accelerated review. And then they still had to agree a clinical endpoint for the confirmatory trial. So if you could just give us an update on, where you think that process is? Is that data generated? And what do you think the clinical endpoint that will be needed for approval will be? Thank you.
Paul Hudson: Thank you, Graham. Brian, ALTUVIIIO.
Brian Ford: Yep. So first and foremost, as you all know, we have this 30-day program, which has been quite helpful for us. We’ve seen that about 90% of the patients that go into that program get converted to commercial, which is really fantastic. And as you have said, it’s going to go down. It was at 20% previously. The patients have gone through the program, it is at 14% now. We anticipate it to go down to between 8% and 5%. And probably it will stabilize somewhere around the 5% range in the coming years.
Paul Hudson: Thank you, Brian. Houman?
Houman Ashrafian: Thanks for the question. Excellent question. Just to call out, we don’t own the asset yet. So we’re beginning to dig into that question. As you will fully appreciate, there are ongoing discussions with the FDA, both in terms of, as you say, bioavailability and bioequivalence with native Alpha-1-Antitrypsin and the right endpoint. But we’re deep in those discussions. And in fact, even last week, we were in conversations with the Alpha-1 Foundation Patient group to consider exactly how we move this forward. Thanks for the question and watch this space.
Paul Hudson: Thank you.
Eva Schaefer-Jansen: The next question is from Simon Baker from Redburn. Simon? Okay. So maybe I move to the next question from…
Simon Baker: Hi, can you hear me, sorry?
Eva Schaefer-Jansen: Yes, we’re good.
Simon Baker: Yeah. Hi. Thank you. Sorry. Can you please provide more color on your view of the potential of CEACAM5 as a targets given the recent tusamitamab ravtansine [fader] (ph). And second one, again, on Beyfortus. We’ve seen this strong uptake in US. But is there any group or payer channels or regions more strongly represented than others at ADC? Thank you.
Paul Hudson: Okay. Thank you. CEACAM5, given the tusamitamab data and maybe some thoughts on the different payload and is it still a valid target?
Houman Ashrafian: Thanks for the question. Excellent question. We continue to believe, based on both our precision medicine computational biology approach and classical immunogenic chemistry, the CEACAM5 is a highly specific and highly expressed target. Its density profile is well suited to an ADC approach as you call out correctly. The previous molecule with a DM4 payload, sadly, did not provide the high efficacy bar that we put in order to serve patient value. We believe, for a number of basic biological reasons, the Topo1 payload on the current molecule, both at preclinical level, but also now in clinic shows significant promise. The short answer is we remain optimistic about CEACAM5 ADCs.
Paul Hudson: Thank you. And, Beyfortus, in particular the…
Thomas Triomphe: So I assume, Simon, you’re talking about the payout coverage in the US. First of all, a significant part of [indiscernible] coverage is to the VFC program. So for the public part, it will converge very well. And for the private medical side of things, I didn’t check very recently, but a few weeks ago, we are already way more and way above 90% payor coverage in the US. Just a few months after that. So I don’t see any problem at all in terms of payor coverage. It doesn’t present, but there might be a few practitioners or a few HCPs that, of course, want to go slowly because we want to make sure that they will be reimbursed and probably covered. But what we’ve seen in the US over the past few weeks, I think it’s now something from the past. I’m very confident for 2024 in the US.
Paul Hudson: Yeah. Just to build on Simon’s question, of course, you referenced the US, but maybe to share some of the enthusiasm they’re seeing from different countries in Europe?
Thomas Triomphe: Definitely. I think that you know that it’s well known that in Europe, if you look plenty of previous historical benchmark. Vaccine entries in Europe normally takes a few years in terms of progress because there is a recommending body, there is no reimbursement decision and its early stage. We are seeing a lot of European countries that are trying to accelerate that process in order to make sure that Beyfortus goes earlier for protection.
Paul Hudson: Thank you, Thomas. Next question?
Eva Schaefer-Jansen: The next question comes from David Risinger from Leerink.
David Risinger: Yes. Thank you very much. So I wanted to say thank you and best of luck to you JB. And I have two questions for Paul and you please. First, can you provide color on the outlook for spending growth in 2025 and also discuss the potential for operating leverage beyond 2025? Thanks very much.
Paul Hudson: Thank you, David. Okay, JB?
Jean-Baptiste de Chatillon: Yeah, thank you very much. Yes, I can try to do that because the question is pretty simple and I can lay it out for you. We enjoy a steady growth and this is with us for many years ahead now with no LOE in front of us and you heard Paul mentioning this underlying growth that we are enjoying when you neutralize the impact of Aubagio. So, it’s pretty easy to see that we are going to enjoy this growth. We said that we would increase in ’24 and that’s why there is a bit of a crush in ’24 because we increased EUR700 million R&D, while other programs are still running like tolebrutinib, COPD, large phase — multiple Phase 3 programs. Those programs will end in 2025 and the oncology to I&I reallocation plus our efforts in terms of the cost reallocation will fully kick in, in 2025.
