Now as per the heart of your question on supply. We have full speed, both AstraZeneca and us are working on extending our industrial network as we have mentioned before, together. We are adding not — we’ve already added, of course, packaging lines, we’re adding filling lines as we have discussed altogether. And as we speak today, we are, every single day, filling new Beyfortus syringes for the coming season. We’re going full speed as we discussed also. Of course, while we are currently manufacturing and filling doses, it will then depend as to the release of this product as per the speed of approval on these two filling lines by the regulators, notably, U.S. FDA and EMA, especially. So we believe that with all the elements we’re putting together with our partner, we’ll be able to have this supply release in due time for the coming Northern Hemisphere, which is why we are very confident in our ability to reach blockbuster status.
To be more specific beyond that will be what we will discuss together at the Q2 earnings call when we’ll have more news from our supply perspective, and this — regulators.
Paul Hudson: Yeah. And thanks, Tom. And I think everybody AstraZeneca, ourselves, everybody is doing the very best because the demand is so significant and Q2 is a much better moment to give you much more facts as we have them frankly. Next question?
Operator: Yes. Next question from Tim Anderson from Wolfe. Tim?
Unidentified Analyst: Hi. This is Brian [ph] on for Tim. Just two quick ones from us. After the EPS reset in 2024, you talked about a strong rebound in 2025. Consensus has growth being around 15% in 2025. Any comment even if only directionally on that figure? I know you might not say anything right now, but anything you might want to call out, such as uncertain variables that might jump out? And then a second question on OX40. You’ve said previously that this might be your most important pipeline drug similar to Dupixent, but you capture full economics. Just want to ask how derisked do you think this asset is at this point in terms of how Phase III trials might read out? And whether you can confirm that there might potentially be earlier readout potentially in 2025?
Paul Hudson: Okay. Thanks, Brian, asking for a friend. I would say, François, any comment? I mean, to be clear, I don’t want to put you on the spot, but we just had strong rebound. So is there any other color you can give?
François-Xavier Roger: No, Brian, what I can tell you, I don’t want to quantify the EPS but we are very confident about it. I think we have the building blocks, starting with the growth profile that we have today. And if we — you put aside already, even you can see it in the first quarter of 2024, some of the exceptional items, the negative ones like AUBAGIO and the comparison base for COVID-19 sales, for example, we are already on a very strong platform in terms of growth today, and which gives you a fair illustration of where we can be in 2025. But I think it’s too early to quantify it today. And I would not like to give guidance for 2025 at this point in time.
Paul Hudson: Thank you, Houman on OX40-Ligand?
Houman Ashrafian: Yeah. Let me respond to this very briefly. I presented the data earlier. Super excited by the data, three points, rather this is a biologic, which has been a large number of patients, it’s likely to be extremely safe, particularly compared to anything else that’s out there. It’s highly well tolerated. The dosing interval, extremely interesting. And importantly, off-drug disease suppression is important. So there are only three comments to make on this. One is, you said how optimistic are we, very optimistic, but we’re optimistic because it may also have the opportunity, and this has been echoed by external commentators to have the potential to reduce atopic march and the progression of disease particularly in those with earlier atopic disease, point one.
So number one is we are bullish for that reason. Number two is, mechanistically, it’s kind of interesting, because it addresses both TH2 as well as TH17, TH22 pathways, which impact on our broad ethnics populations. So number two is it’s derisked from that perspective. And number three is clearly, we’re taking it forward in a multiplicity of indications, some of which we’ll read out this year. So the quick answer to your question is we’re driving the studies as hard as we can. We’ve got four Phase IIIs in flight, we’ll drive them to completion in an orderly manner as possible. And bear in mind as a biologic, feel optimistic that we have been able to quantify it’s risks and benefits.
Paul Hudson: Great. Thank you. Next question.
Operator: Yes. Next question from Emily Field from Barclays. Emily?
Emily Field: Hi. Thanks for taking my question. The first is just piggybacking off of the earlier Dupixent launch and COPD answer. The contrasting thought between the biologic ramp is going to take some time, but that pulmonologists are very familiar with Dupixent, obviously. As we’re thinking about this launch is this one that is going to require a great deal of incremental promotional spend? And then on ALTUVIIIO, you mentioned taking share from therapies other than LOCTITE. Are you seeing more share take from HEMLIBRA as that a decline in US in the quarter? And then big focus of their call yesterday was on the potential competitive threat from Mimi [ph]. Are you seeing that as a potential threat to ALTUVIIIO or do you see that more as posing a threat to bispecifics? Thank you.
Paul Hudson: Okay. Brian, over to you, COPD ramp. And I think the challenge is if pulmonologists know Dupixent already, why should it take some and what will be the cost of doing it?
Brian Foard: Yeah, I think there’s a couple of things in there. And so I think just as we said before, as you bring in a new therapy like this, any patient population, you’ve got to educate the patient population. You’ve got to educate the physicians. There’s a lot to be done there to where it’s not just to come in and take share game. It’s going to be one of those things where it’s bio penetration. We’ve seen this very well in atopic dermatitis. As you see in AD, here we are we’re nearly eight years in and the bio-penetration rate is 11%. So it takes time, it takes effort. The good news about cost, and I think the expense is, if you think about it, we’re very efficiently set up because we’re already set up across the alliance actually deeply in the pulmonologist offices across all countries.
So from an OpEx standpoint, there will be a lot of efficiencies there because this will be our second indication in the same offices. So we, of course, will spend to support this launch. It’s absolutely a critical launch to reach as many patients as possible, but we certainly see some efficiency there and the way in which we’re set up.
Paul Hudson: Thank you. ALTUVIIIO share any business coming from non-factor and a comment on Mimi?
Houman Ashrafian: Yeah. A couple of things there. I think it always goes back to the patient and the unmet medical need. So if you think about this patient population, it’s all about efficacy at the end of the day. And previously, where you speak about HEMLIBRA, that was more of a convenience play than anything else. While effective, it was more of a convenience play, the first subcutaneous product. So I’ll break it into two pieces. ALTUVIIIO is doing exceptionally well. We couldn’t be more pleased with the launch progress because, again, the physician and the patient population really understood that for a single dose, you can actually have near normal factor levels for an entire week. And that’s really changing the game in the offices.
Now where are we primarily taking business from? We always said we primarily take it from factors, because we believe all patients that are on factors should be moved to ALTUVIIIO. And the factor marketplace is about 60% of the marketplace still today, 60% to 65% of the marketplace. So that is primarily where we’re taking business. Two-thirds of our switches are coming from competitives, one-third is coming from LOCTITE again, a factor that should be switched. Now as it specifically relates to HEMLIBRA, and then we’ll talk about the competitor that’s coming, I definitely think HEMLIBRA should be more nervous about the competitor than us for sure. But we’re taking about 10%, about 10% of our business is actually coming from HEMLIBRA. It wasn’t what we anticipated necessarily, but again, I think it goes back to the efficacy side of things.
So again, we couldn’t be more pleased with the progress so far. A lot of our physicians more than 80% of the physicians have prescribed and we’ll reiterate that they continue to increase their prescribing moving forward. So again, we’re off to, again, a really good start as we hit almost the first year mark for ALTUVIIIO.
Paul Hudson: Thank you, Brian. And of course, as we watch the market evolve, you’re right, I think we took more patients from HEMLIBRA than expected and probably because they’re trying to chase efficacy down to the once a week, which meant once a week convenience was roughly the same. I think when HEMLIBRA set the bar and we’re trying to find some new convenience standard. And I think this month or perhaps even eight weekly reduced around, I think that could be a new level two. So the market is clearly going convenience versus efficacy in the trade. So I think we’re going to be well-positioned. Next question.
Operator: Yes. Next question from Emmanuel Papadakis from Deutsche bank.
Emmanuel Papadakis: Thank you for taking the questions. Maybe a question on cash flow, first of all, please. François, you mentioned some caution on the outlook for this year. I think you mentioned some onetime adjustments for prior year rebating. Perhaps you could give us a bit of color maybe in absolute sense, cash flow last year was around €11 billion, free cash flow was above €8 billion. So what should we be thinking of for this year? And you did have some rather outsized restructuring costs in Q1 over €700 million. So where is that likely to land for the full year? And what proportion of that is cash and a lot of capital working capital outflow in Q1, which drove a negative cash from operations, which is also rather unusual. So comments around those would be very helpful. And then a quick one on teased flat again, a few quarters in a row, still confident on blockbuster potential? If so, what gets us there? What are the time lines? Thank you.
Paul Hudson: So François, you do that and then maybe, I don’t know, Olivier want to comment on Tzield?
François-Xavier Roger: Let me start. Good afternoon, Emmanuel. On the cash flow, so it is essentially the fact that the decrease already in Q1 is essentially coming from the lower gross to net in Lantus. As you know, we are booking lower, but we have to pay from a cash flow point of view, to rebate on a higher base, at least in Q1, we will have a little bit of an impact as well in Q2 and Q3. This has impacted our cash flow significantly in Q1, and there will be a little bit of it the next two quarters. Obviously, this will remain for the full year. So I just wanted to flag the fact that this is kind of a one-off that will impact our cash flow for the full year. I don’t want to quantify it because there are other moving parts, but this is a fairly significant one-off impact.
On the restructuring costs, it’s essentially linked to many of the projects that we have already announced part of it is actually obviously hitting France, as you know, because it’s in the public domain as well. It’s not necessarily a cash item that will be significant in 2024. It will spread over the next two years, partly, but some of it could potentially impact the end of 2024.
Paul Hudson: Thank you. Olivier comments on Tzield?
Olivier Charmeil: Comment on Tzield. So we see a positive evolution and a slight acceleration growth in terms of screening and in terms of infusion rates, Q1 versus Q4 where we have higher infusion in Q1, we have more — we have higher infusion in pediatric patients, which is for us a good signal, which means that we are progressing. Infusion have accelerated, driven by more field force execution and better coordination along the patient journey. Payers coverage is good. It’s not a barrier to utilization. We said from the beginning that it would be a slow burn. We are shaping a market that didn’t exist. There was no screening because there was no treatment. We know that it will take some time, but we think that it’s worth the effort.
It’s about creating the awareness and making sure that both awareness at the patient level, at the family level but also with HCP is developed. We are very encouraged by the consensus guidelines that are being developed a white paper from ADA as that was recently developed, and there are a lot of activities to activity in the congress of ADT with GRF making and aligning a lot of medical society towards guidelines. So overall, it’s going to be a slow burn, but we are confident that in the future, it will continue to progress. We think that it’s worth continuing to invest, and this is reinforced by our exchange with KOL and clinicians that really gives us confidence that with Tzield we have the first and only disease-modifying therapy in type 1 diabetes.
