Susan Galbraith: So because of key survival benefit that we’ve seen is very clinically meaningful with FLAURA2. And, of course, the comparator is something that’s already proven overall survival benefit in the first line setting of lung cancer, which is monotherapy Tagrisso. So I think what we’re hoping to see is, maintenance of that improvement in PFS being carried through to the PFS 2 and a trend in OS, I think is very reasonable to expect. But, obviously, as the data mature, we’ll continue to look at the OS endpoint.
David Fredrickson: Thanks, Susan. And, Tim, I think maybe just to build off of this, I think there’s also an important tangential question just in general around the importance of overall survival as there’s consideration for choices. And I think that you referenced the editorial, I think you hear this in the editorial, but also we hear this from the community as well. That in selecting a treatment, the benefit risk profile inclusive, of course of efficacy, the side effect profile, as well as the administration are all important factors that will come into this. So within that context, FLAURA2 is certainly something that we have heard very much as an option for those patients who would benefit from intensification brain mets, LA-58r.
And on top of that clinicians are pretty well versed in the side effects that are associated with chemo and there’s the ability to discontinue the chemo and FLAURA2, if approved and continue on with the monotherapy. But we also hear and know that the monotherapy is an option that we anticipate will continue to be a really important option for the majority of patients all greater than three years overall survival demonstrated proven and understood in a tolerability profile. That’s well managed.
Sharon Barr: Sure. Thank you for the question about continuing to build our portfolio. I hope that this morning I’m conveying a story that we continue to build a strong cardiovascular, renal and metabolic portfolio with multiple medicines to treat obesity, Type 2 diabetes, dyslipidemia, hypertension, chronic kidney disease, and heart failure. So where we see opportunities to further strengthen that portfolio, we will move forward with a sense of urgency. We never comment on business development deals that are in progress or future opportunities that we continue to scan the landscape and understand what might fit best into this growing portfolio.
Pascal Soriot: Thanks, Sharon. And maybe let me add biopharma cardiovascular in particular remains very important to this company. And for the little internal friendly competition we have Ruud beat Dave by 100 million in the first nine months of the year. So very important part of the company. Anything you want to add on.
Ruud Dobber: No. Just to reinforce that, of course, we are excited about our internal pipeline also in obesity. It was a long-acting MLN, the GLP-1 glucagon dual agonist. But as Sharon said, we’re always looking around for something what can add value is making strategically sense. But all in all, I think we’re very pleased with the progress we are making in our pipeline.
Pascal Soriot: All right. Next question is Emily Field at Barclays.
Emily Field: I wanted to ask about the Volrustomig, actually, I saw you started Phase III in cervical and lung and you also had renal data at ESMO. Just how broad of a Phase III program are you intending on running? How many tumor types? Secondly, when could we see the combination arm from the TL-4 study that combines the Volrustomig with Dato-DXd. And then my last one, just how much broader in terms of addressable patients with LAURA add to the Tagrisso patient pool. Thank you.
Pascal Soriot: Thank you, Emily. Susan, could you go over the first two Volrustomig questions and Dave, you could address LAURA question.
Susan Galbraith: Yes. So again, I would say that we see the positioning of both Volrustomig and rilvegostomig as being appropriate in different segments of the patient population that are currently treated with checkpoint inhibitors. So I think Volrustomig has a place where CTLA-4 inhibition, particularly adds value. And those are the areas that we will concentrate on. I also think there’s emerging data from rilvegostomig, which will probably share at congress next year. And again, we please note that we have actually started our first Phase III trial with rilvegostomig building on the great data that we saw with TOPAZ in the biliary tract setting. So I think there’s great potential for this. We are examining both rilvegostomig and Volrustomig combinations with our ADCs in different tumor types. And we will, again, probably share updates on those in the next 12 to 24 months.
David Fredrickson: On LAURA, Emily, just in terms of the opportunity here, let me start with the headline, which is I think this is a sizable opportunity and an important chance for us to, if positive and approved, be able to meaningfully catalyze the growth within the area. We know from the specific work that we’ve done that there’s a significant number of patients that are diagnosed that are stage-3 unresectable. We also know that many of these patients are not getting for very understandable reasons treatment with who are EGFR mutated with IO. And so there’s a very good opportunity that’s there. And I think that this will be probably the most significant Tagrisso growth driver that I would see as incremental coming into the near term. And we look forward to next year’s read out.
Pascal Soriot: Yes. Important growth driver across the world very much, of course in Japan where this EGFR mutations are coming. And I think in China also beyond the growth potential also very nice differentiation in the market, as you know, is very, very competitive. The EGFR market is very competitive. So clearly an important addition from a differentiation viewpoint and promotional opportunity for the Chinese team. Next question is James Gordon, JPMorgan.
James Gordon: First question was on the oral GLP-1. And the question was, do you think the products going to be competitive on weight loss, versus other orals that are well ahead in terms of development? Or is the differentiation going to be much more about the combinability with other oral agents? And if so, which of the combos is it that you’re most excited about? That’s the first question. The second question was RFS-3 I think you started Phase III, MIRANDA, did you do this new high dose carb as you announced in Phase II, in the first two studies over on the [indiscernible], under those or it should be left, and then I think we’re going to wait for the third trial? And then, if I could just [indiscernible], you mentioned potential launch next year, is the expectation about the launch in both the lung and breast cancer so you filed both of those at the end of this year, and launch both of those next year?
Pascal Soriot: Thanks, James. I’m really so happy that I’ve delegated the task to Andy to ask people to ask only one question at a time. Maybe, Sharon, you could take the first one, and again, Ruud, if you have anything you want to add? And then, the second one also, actually, and then Susan will take the Dato question.
