Pascal Soriot: Thank you, Susan. The next question is from Andrew Baum, Citi.
Andrew Baum: First to Sharon. Could you quantify and characterize any liver enzyme elevations you saw in the Phase I with ECC5004? And then second for Ruud with the removal of the AMP cap from Medicaid in 2024, could you quantify for us the net impact on your revenues associated once you’ve taken out mitigating defensive measures? Many thanks.
Sharon Barr: Sure. So I’ll jump in with the answer regarding liver toxicity and ECC5004. In preclinical studies, we saw no evidence of liver toxicity. And in the clinical Phase I study today we have seen no evidence of elevated ALT or AST, which we think is an additional feature that helps us differentiate this molecule from other competitors in the class.
Ruud Dobber: So I will take the second one, Pascal. So regarding your question, Andrew, about the impact of AMP cap, you have seen in the presentation of Pascal, that we are very pleased with the very strong U.S. growth. And that’s primarily driven by volume growth, including Farxiga. Yes, we are expecting in the impact of AMP cap in 2024. But we have very specific brand strategies in place. Overall, we think the impact is manageable, and it will be effective in the guidance we’re going to give for 2024.
Pascal Soriot: Thank you, Ruud. Our next question is from Sachin Jain with Bank of America.
Sachin Jain: I have a couple for Dave and then one for Aradhana. So Dave, half of assertive launched from the end of this year. It’s not an asset you talk about much. I wonder if you could just comment your optimism for the assets and size of the initial indication. Secondly, on [indiscernible], wonder if you could flash out the comments on the slowdown in the U.S. on the [indiscernible] implications to grow the asset into ’24. And then just one for our Aradhana. And you’re not going to like the question, but any early thoughts for ’24 growth outlook, consensus has ’24 EPS faster than ’23. I’m not asking for guide but just pushes and pulls in the ability to accelerate growth in ’24 relative to ’23. Thank you.
David Fredrickson: Great. Sachin, I’m going to take the questions that you asked me just in reverse order. So if I start first with Enhertu. When we take a look at both DB03 and DB04, we are seeing continued opportunity for growth across the globe on both of those. On DB04 specifically, we had seen increase or a bolus effect at launch where patients in multiple lines of therapy, so multiple lines of post chemo coming on to Enhertu just really due to a lack of options for patients in these later line advanced stages. What I’m pleased to say and I think this is actually a really important aspect of Enhertu, the duration of therapy that those patients were able to stay on Enhertu was actually longer than we had even thought. So the bolus actually has been around if you will as part of the TRXs for a longer period of time than we had originally anticipated it might be.
We continue to see nice growth and now the incident share, so I think the DB04 continues to grow and we’ll be moving based upon growth in two factors, one will be incident new patient share growth but then also DOT which I expect will continue to grow. That DOT comment if I could just for a second I think also holds for DB03, where you may recall that in 03, we had 18 months of duration of therapy within the study itself. But we know that more than a third of patients were staying on therapy for greater than 24 months. So we’re continuing to see the 03, DOTs extend. And I think that’s a positive piece within that. As we take a look at CAPI, I share enthusiasm that pivot sort of could be a very important part of our breast cancer portfolio. And then perhaps Susan can talk a little bit about some of the thoughts around the CDP, that goes beyond that.
I do think that it’s most likely that we will see biomarker labels across the globe, though, we do believe that the benefit in the ITT population was an important one. But there’s a pretty significant number of people with breast cancer who can continue to benefit from endocrine based therapies in that advanced setting, and biomarker is still 40% to 50% of that marketplace. So it’s a sizable opportunity. And we are looking forward, hopefully any day now to an FDA announcement and approval.
Pascal Soriot: Before we move to, thanks, Dave. Before we move 2024, maybe Susan, you could comment on other indications that we are considering for CAPI?
Susan Galbraith: Yes, sure. So do you think this is an opportunity in a number of settings where the AKT pathway is important in limiting benefit either in combination with endocrine therapy in both breast and prostate cancer, but also in combination with chemotherapy as well. So as well as the 291 study, we have CAPItello-290, in triple negative breast cancer, CAPItello-292 is in combination with palbociclib and other CDK 46 inhibitor potential as well as a hormonal therapy backbone in the first line. So it’s got Faslodex as the hormone therapy backbone in the first line in CAPItello-292. And then in prostate cancer, we have CAPItello-281, where capivasertib is combined with Abiraterone. And again, that’s focused in p10 deficient hormone sensitive prostate cancer based on the Phase II study there.
But we also have a combination with docetaxel and again, the AKT pathway limits the response to chemotherapy and limits the apoptotic response to chemotherapy. So that’s also an important study. And based on the brocade data set, there’s activity again, across the spectrum of patients, both with and without p10 deficiency in that setting.
Aradhana Sarin: So thanks for the question. Obviously, we won’t give guidance for 2024 on this call. We’ll have to wait for early next year for that. We’re actually going through our budget process right now. And as that concludes, towards the year end, and we present that to the board and then we’ll give our guidance next year. Some of the things that, obviously, you need to take into account some of the pushes and pulls in the 2024, and midterm, including currency movements. As you know, we’ve had very strong growth momentum with our underlying brands. But then, we also have launches for Airsupra and [indiscernible] that Ruud mentioned that we’ll be investing behind. And then, the Phase III opportunities as well as some of these new BD opportunities, including the current product that we talked about on Eccogene. So lots of moving parts. And we look forward to talking to you about that in early ’24.
Pascal Soriot: Maybe some quick addition to 2024. Actually, going back to the question Andrew asked about, AMP cap, since the announcement of this new regulation, we’ve really come up with very modest price increases always below inflation. So of course, the calculation goes back many years, but we still believe that we will have an impact that is substantially lower than many other companies. And as I’ve said it can be certainly managed in the overall forecasting budget, forecasting for the company. So the next question is Tim Anderson, Bernstein.
Tim Anderson: Couple questions on, Tagrisso FLAURA2 is in the New England Journal last night editorial fairly positive, based on [indiscernible] benefit, but really said it kind of comes down to how survival plays out. So the question for you is, your view on whether it hits on survival in a clinically meaningful way? And then, the second question is on obesity. Just further business development from here it seems like if you’re going to push into this space, with external assets, like today’s announcement, made you go all in and do more external deals, there are other assets out there who take a much broader portfolio approach, or conversely, this was kind of one and done. This was going to be your main asset from the outside world. Thank you.
Pascal Soriot: Thanks, Tim. So the first question, maybe we could start with Susan. And then, Dave, I think you could also comment on the commercial relevance of FLAURA2 which we believe is important for many patients. And the second question, Sharon, you could take and anything you want to add, Ruud also please jump in.
