Pascal Soriot: And Mene is not with us in the room but he is keeping an eye on us, so reminding us that we still have a number of read outs last cycle management opportunities in R&I, with [indiscernible], with Fasenra, with [Toso] [ph], so still quite a lot to come in R&I in particular, respiratory. So we move to the next question, Simon Baker at Redburn. Can I ask, we only have a few minutes left, so can I ask everybody to ask one question, if you don’t mind? Over to you, Simon.
Simon Baker: Thanks, Pascal, and I’ll behave myself. On — [indiscernible] questions for you, Susan. The current use of CTLA-4 is really defined by acceptable levels of toxicity, and if your bispecific is better tolerated, that broadens the scope. I’m specifically thinking about lung cancer and PD-L1 greater than 50%. If all of Lung02 is focusing on less than 50%, are you planning to look at PD-L1 high as well? Thanks so much.
Susan Galbraith: So I think in the PD-L1 high group, this is the place where at the moment, based on the current data that we have, that the addition of TIGIT seems to make a particular difference in that setting. So we obviously look at the emerging data across our bispecific portfolio, but what we’re doing in terms of the initial Phase III trials that you’re seeing is focusing on the area where we think get that added benefit from CTLA-4 inhibitor. It is better tolerated than just any co-administration of the two antibodies separately rather than in one drug, where you’ve only binding CTLA-4 in the presence of PD-1. However, if you compare, you are still getting some increase in toxicity. So I think we’ve got a much, much lower rate of the diarrhea and colitis that you see with CTLA-4 inhibition.
But we have still seen some increases in liver enzyme elevation, and that’s really what we try to optimize for when we’re optimizing for the dose at 750. So we have an acceptable way of drug discontinuation and holidays based on that. So I think we still need to make sure that we’re optimizing the patient population that we’re choosing for the relevant checkpoint inhibition profile, and that’s what we’re aiming to do across our bispecific portfolio.
Pascal Soriot: This is the beauty of this portfolio, and volrustomig is a more logical option for PD-L1 high, Simon, and the CTLA-4 combination of volrustomig is a better option for PD-L1 low in lung cancer. So we’ll move to the next one. [Ajay Kumar] [ph], HSBC.
Unidentified Analyst: Just one question on the long-term financial targets, you indicated that you want to achieve faster than the industry growth. Can you run us through how you’re thinking about capital allocation today in terms of, for example, you highlighted GLP-1 acquisition or you just started trials on bispecific that will position you to be there. So what is the capital allocation regardless that you’re following today that gets you to an answer? Whether there is, you won’t get success in everything, but what gives you the confidence that you can deliver that industry-leading growth?
Pascal Soriot: Thanks, [Ajay] [ph]. Aradhana had to step out for a minute, so let me address your question. First of all, we don’t give long-term guidance. The only thing I will say about the long term is what we said before remains our goal, so there’s not much change there. And in terms of a specific question about capital allocation, as Aradhana said a bit earlier during her comments, the priorities for us are to invest in our pipeline, reduce debt and pay our dividend, so there’s no change there. And certainly, we want to continue building our pipeline. But the — each time we build the pipelines for [indiscernible] like we’ve just announced this morning, this additional growth, we believe that we can deliver industry-leading growth from ’25 to ’30 and beyond based on what we have today.
So anything we had actually will help us grow even more during the period and beyond. So we’re always looking at today, tomorrow and the day after, the day after being new technologies like cell therapy that we want apply to oncology but also immune diseases, as Sharon mentioned, T cell engagers, gene therapy for rare diseases. In the midterm, of course, which is what I call tomorrow, is actually a large Phase III pipeline. So that’s really what we try to do. The next question is Emmanuel Papadakis, I’m rushing a little bit, from Deutsche Bank. But we only have a few minutes, and I’d like to have everybody first to ask your question. Emmanuel over to you. Well, go ahead.
Luisa Hector: Luisa Hector from Berenberg, actually.
Pascal Soriot: It’s not about the screen that I have in front of me, saying, but it’s great to hear you. Go ahead Luisa, then we will look back to Emmanuel, that’s okay.
Luisa Hector: So on [indiscernible] at ESMO, it became clear that this drug is absolutely delivering on the promise of ADPs in the EGFR subgroup of lung cancer. I just wondered why you think this is? And whether you need to see any more data before you could consider starting Phase III in frontline EGFR in combination with Tagrisso? Thank you.
Pascal Soriot: Thanks. So it’s a good question for Susan.
Susan Galbraith: Yes, sure. Thanks for the question. So yes, in the EGFR subgroup, we did see really good activity with the hazard ratio of 0.389 group in the randomized study of TL01. So we’ve also got data from the ORCHARD platform study looking at the combinability of Dato-DXd with Tagrisso. So I think that’s an important piece to also put in place. So I think it is encouraging. Obviously, as we’ve already said, we’re going to be expanding the portfolio of Phase III trials that we have for Dato-DXd, and you’ll see more of those trials in the coming months. But this is a place that obviously we can build on the great data that we just see with FLAURA2 by looking at the combination of Tagrisso with chemo, and you have the potential then to improve on the chemo piece. So I think it’s an interesting area. And, obviously, we’ll be posting more trials in the coming months.
Pascal Soriot: Thanks, Susan. Emmanuel, over to you.
Emmanuel Papadakis: Quick question on vemircopan the discontinuation for lack of efficacy in PNH. What cross [read does] [ph] have to the ongoing myasthenia gravis renal studies? And where does that leave your oral strategy and ability to defend against potentially newcomers like [Takapan] [ph], et cetera? And then if I got a very quick follow-up for Ruud, you didn’t mention China VBP [indiscernible] next year. Are you no longer expecting that to be a headwind for revenues? Thank you.
Pascal Soriot: Okay. Marc, do you want to cover the first one?
Marc Dunoyer: Yes. So to answer your first question on vemircopan in PNH. I mean, PNH, it’s absolutely essential to have a very high control of the disease, and we recommend in PNH the dual therapy between danicopan and Ultomiris. Ultomiris has a very sustained and strong efficacy over time. I believe it’s going to remain the standard of care. Vemircopan has shown efficacy but not as high as we want it to be. Regarding the read across other indications, we are still continuing Phase II studies in MG, as you mentioned, but also in several renal indication, and we are hopeful that this indication will be successful.
Pascal Soriot: Maybe just one quick addition to what Marc said. I mean they are, as you probably saw with iptacopan showed some sign of potential breakthrough IVH. So that’s why we believe C5 potentially combined with danicopan is really the best option here. Over to you Dave.
David Fredrickson: Yes. Sorry, Emmanuel, so it’s clearly Farxiga is not listed in so-called batch 9. It could go into the VBP batch 10, but that impact will be only seen then in mid late 2024, so we simply need to wait till batch 10 is announced.
Pascal Soriot: Last thing with China, and Farxiga is we will, as we’ve said before, we will what we call consumerize it just like we did with Crestor. I mean the volume potential is still gigantic in China. The price is relatively low, so we can definitely consumerize it and operate in a private market and deliver to patients at home for a very low cost. So we believe we should be able to transition. There will be — when we go VBP and we don’t know exactly when because as Ruud said, it could be further delayed. When we go to VBP, we should have an initial drop and like we saw with Crestor and I hope, and belief is that it can after that grow in volume. We take the last one question from Peter Welford, Jefferies.
