So I think we manage that and we provide that the top-down discipline, but it’s a tough situation. I think if you asked Mark or Susan or Sharon, they’ll always tell me we don’t have enough money for all the exciting projects that we have. So — so we try to maintain that balance.
Pascal Soriot: Thanks, Aradhana. Maybe a couple of additional points. First of all, beyond the prioritization that Aradhana covered very well and the use of technology to make ourselves more productive, we also have launched and are implementing a redeployment of our footprint. And so we are, for instance, leveraging Canada, Toronto in North America, Barcelona in Europe. So we are going through a process by which we locate in the strategic centers jobs should be located there. And then we have a nearshore and a far shore strategy, so we are leveraging our sites in Guadalajara and also in India for some roles, so we’re doing all sorts of things that help us manage the cost of R&D. We’ve been internalizing the conduct of our clinical trials.
First of all, we believe that we’ll deliver a better execution of our trials if we do it with our own clinical teams, but also, it reduces our cost when we internalize. So ultimately, we stick to what we said before, which is low 20s R&D on revenues. Some people have said what is [ low 20s ]. If low 20s is low 20s, if we meant more than this, we probably would say mid-20s or something like this. So it’s low 20s, and I just want to reconfirm this is our ongoing target.
Susan Galbraith: Yes. Thanks for the question about saruparib, this is another program that I’m really excited about. I think we’ve learned a lot about the right patient populations to treat with PARP inhibitors during the development of Lynparza. But saruparib has this improved profile which enables clear improvement and tolerability, enables you to hit the target even harder, and I think that has the potential to lead to actually better efficacy than we see with olaparib. So it’s great to see the first Phase III trial starting, you’ll see more coming. And I think one interesting area is the potential for this to have combinations. So saruparib in combination with ADCs is absolutely something that we’re exploring, and we’re encouraged by the early data that we’ve got, but it’s a little early to be sharing those externally at the moment. Probably it will be another 12 months before we show those, I’d expect.
Pascal Soriot: Next question is from Christopher Uhde at SEB. Christopher, we can’t hear you.
Christopher Uhde: Can you hear me now?
Pascal Soriot: Yes. Perfect. Go ahead.
Christopher Uhde: All right. Great. So my first question is for Sharon. Now that you taken over, I think we have a pretty good idea of what the strategy is for CVRM. Perhaps you could talk a little bit about what the R&I sort of big picture strategy is overall? And in terms of — so R&D strategy and integrating that with commercial strategy and how to execute on it? And then my second question is on Farxiga. And maybe here, I’d like to start by congratulating Mene and his team, even though he’s not here today, on the successful reoffer of zibotentan. I guess it’s his brain child and arguably the zenith of his achievements at AZ. So a small percentage of patients that are eligible for SGLT2 actually get it across the each approved indication.
Is the NRx split still even across the indicated patient groups and how much gas is left in the tank in the U.S. and EU across those indications? We’ve got Dato, MI toplining positively, so how much impact can that have? And beyond it, are there any remaining steps you can take to convince prescribers or payers that a larger proportion of patients should be adding on SGLT2 on top of metformin or statin or BP meds or whatever before you start to bring Farxiga combos into the picture? So like are the specific patient subgroups, for example? And there’s a logical follow-through. When the SGLT2s lose exclusivity, do you anticipate any substantial step-up in breadth of use, what might that look like? And does that impact how you view the opportunity for the novel Farxiga combo regimens like zibotentan?
Pascal Soriot: So Sharon, R&I?
Sharon Barr: Yes. So I’m in a very lucky position of stepping into a very strong biopharma organization with a foundation that was built over many years by Mene, and I’m grateful for both the incredible portfolio that was established as well as the extraordinary team of scientific leaders that I have the privilege of working with. So as we look forward to how we’re going to continue to grow and invest in R&I, let’s think a little bit about the successes that are already beginning to drive value for the portfolio. So looking towards Saphnelo, we have 3 Phase III studies ready to initiate. In fact, the DAISY study in sclerosis just dosed, so that’s a Phase III study already initiated with 2 more, which we expect to launch early next year.
So we’re very proud of the potential of Saphnelo, which was put in place through internal discovery and development programs, and we’re beginning to see delivery of that promise. Also, a strong contender in our portfolio is tozorakimab which, as we mentioned earlier, is differentiated for the competitors because it is able to inhibit both the ST2 and the RAGE/EGFR pathways. And so we really see a wonderful opportunity there to target the breadth of respiratory disease and to be able to offer a better outcome for patients. So as we think about how we continue to build on our success and move forward, as we’ve mentioned, we’re very interested in growing our footprint in treatments for immune-mediated diseases, and this is a continued build within the group as we expand both our capabilities as well as our capacity and we think about the new modalities that will best serve patients moving forward.
So we continue to expand our pipeline and to think about what the treatment of the future maybe, and for a hint of the way we are thinking, Susan told you earlier about investments in cell therapy and the promise of those who have demonstrated in oncology. And we have seen early clinical data published by academic experts who have demonstrated the promise for cell therapy in patients with autoimmune disease, so we’ll continue to explore these capabilities and evaluate the potential for that within our portfolio. I hope that gives you some color that will also help us share our excitement and growth in respiratory and immunology.
Ruud Dobber: And let’s not forget, before I come to the Farxiga question, there’s still a high unmet medical need in our core indications in [indiscernible] despite all the progress we have made in the last few decades, but many patients are still suffering from severe exacerbation, lung damage, so there’s still a very big untapped opportunity in those diseases. Coming back to your question regarding the growth potential of Farxiga, it’s still very substantial, Christopher. Just to give you some numbers, currently, almost 1/3 of the new prescriptions are going to Type 2 diabetes, but more than 2/3 are going to CKD and heart failure. And the penetration in those 2 diseases is at the moment, despite all our efforts and also from the competition, is only 15% to 20%.
And hence, there’s still a very substantial upside moving forward. Very pleasing to see that most of the guidelines around the world have now adjusted their guidelines and SGLT2 are now one of the fundamental pillars of the treatment of heart failure patients, and the same is true for chronic kidney disease. So in that sense, the volume opportunity is very substantial. And your question about LOE, and let me reiterate again, we have a very, let’s say, fragmented period of LOEs with Farxiga. 2026, the United States, but only 2028 in Europe. And beyond that, we see a very strong growth in emerging markets wherein some of those markets, roughly 10 markets, we have already lost LOE but still the brand is still growing very fast. So I’m not going to say that there’s no impact on LOE, of course, there will be an impact of LOE.
But clearly, the combination products hopefully will compensate for that loss in the second part of the decade. And we remain very bullish about the growth potential of the products let’s say, in the next few years.
